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  • 1
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    Clofarabine, Idarubicin, and Cytarabine (CIA) As Frontline Therapy for Patients Younger Than 61 Years with Newly Diagnosed Acute Myeloid Leukemia (AML)
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 1550-1550
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1550-1550
    Abstract: Abstract 1550 Background: Clofarabine is a second generation nucleoside analogue with activity in adults with AML. A recent randomized phase III study in AML relapse showed higher response rates and better event-free survival with the combination of clofarabine and cytarabine (CA) compared to cytarabine alone. We have also reported the feasibility and safety of the addition of idarubicin to CA (CIA) in a previous phase I and II study. To explore this combination further, we conducted a phase II study of CIA in pts 〈 /= 60 years with previously untreated AML. Patients and Methods: Patients (Pts) were eligible if they were 〈 /=60 yrs of age with newly diagnosed AML. Pts were excluded for ECOG PS 〉 2, cardiac ejection fraction 〈 45%, or active and uncontrolled infection. For the first 30 pts, induction therapy consisted of Clofarabine 22.5 mg/m2 iv daily (days 1–5), Idarubicin 6 mg/m2 daily (days 1–3), and Cytarabine 0.75 g/m2 daily (days 1–5). From pt 31 onward, induction doses were amended to Clofarabine 20 mg/m2 × 5, Idarubicin 10 mg/m2 × 3, and Cytarabine 1 g/m2 × 5. Pts who have not achieved a complete remission following the induction could receive one re-induction course. Pts in CR or CRp continued with up to 6 consolidation cycles with Clofarabine 22.5 mg/m2 × 3, Idarubicin 6 mg/m2 (days 1–2), and Cytarabine 0.75 g/m2 × 3, subsequently amended to Clofarabine 15 mg/m2 × 3, Idarubicin 8 mg/m2 × 2, and Cytarabine 0.75 g/m2 × 3. Supportive care was standard. Pts ≥ 50 yrs were admitted to a laminar air flow room for the duration of the induction. Results: From April 2010 until August 2011, 51 pts have been accrued with a median age of 49 yrs (range 19–59): 33 pts (65%) with de novo AML and 18 pts (35%) with secondary AML (18 related to MDS, 7 related to therapy). Three pts (5%) had a PS of 2. Median WBC at diagnosis was 3.4 × 109/L (0.6-92.3). Thirty-three (65%) pts had abnormal cytogenetics (21/33[64%] poor risk and 5/33 [15%] intermediate risk). Molecular profile: 6 pts (11%) had FLT3/ITD, 3 pts (6%) CEBPA, and 8 pts (16%) NPM1 mutations. Thirty-five pts (69%) achieved CR and 1 (2%) CRp for an overall response rate (ORR) of 71%. 61% pts (31/51) achieved CR following one induction cycle. 18% (9/51) pts required a re-induction and 44% (4/9) of them responded after the re-induction. Responding pts received a median of 2 courses (1–8) courses. With a median follow-up of 23 weeks (3–36+) median remission duration has not been reached with a 1-yr remission probability of 85%. Ten pts (19%) died on study including 2 (4%) who died 〈 28 days from treatment start (one from septic shock and multi-organ failure, and one from Steven Johnson syndrome). Median overall survival (OS) for responding pts has not been reached (2–36 weeks). One-yr survival probability is 65%. Sixteen pts (31%) proceeded with an allogenic stem cell transplant in CR1. Most toxicities were 〈 /= grade 2 and included rash (41 %), nausea (29%), diarrhea (23%), elevated transaminases (21%), and elevated bilirubin (17%). Toxicities 〉 grade 2 included elevated bilirubin (4%), hypokalemia (4%), cellulitis (4%) and seizure (1%). Myelosuppression was ubiquitous but prolonged myelosuppression 〉 42 days was infrequent. 76 % (39/51) pts had neutropenic fever. Conclusion: Clofarabine, Idarubicin and Cytarabine achieve a response rate of 71% in patients 〈 /=60 yrs with previously untreated AML. Induction mortality was low and the toxicity profile was expected and manageable. Longer follow up and comparisons with standard induction therapy will be needed to further assess the role of this combination in AML therapy. Disclosures: Off Label Use: Clofarabine, use of Clofarabine in AML. Ravandi:Genzyme: Research Funding. Kantarjian:Genzyme: Research Funding. Faderl:Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.1550.1550
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 2
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    The MD Anderson Cancer Center (MDACC) Experience with Ruxolitinib, An Oral JAK1 and JAK2 Inhibitor, in Myelofibrosis: Long-Term Follow-up Outcomes of 107 Patients From a Phase I/II Study,
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 3851-3851
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3851-3851
    Abstract: Abstract 3851 Background: Myelofibrosis (MF) is a myeloproliferative neoplasm associated with splenomegaly, debilitating symptoms, cytopenias and progressive bone marrow fibrosis. Survival in MF is poor, and effective therapy is lacking. Ruxolitinib (INCB18424) is a JAK1 and JAK2 inhibitor with established clinical benefit in patients (pts) with MF (Verstovsek S. J Clin Oncol 29: [suppl; abstr 6500], 2011) by reducing spleen size and improving MF symptoms & quality of life. Objective: Aim was to identify potential correlates of overall survival (OS) of MF pts receiving ruxolitinib. This study was based on a subset analysis of an open-label single-arm phase I/II trial (INCB18424–251; NCT00509899). Methods: 158 adult pts with primary or secondary MF were enrolled in the parent trial; most received ruxolitinib at doses of 10–25 mg PO twice daily. This updated analysis focuses on 107 pts enrolled at MDACC: 63 were high, 34 intermediate (int)-2 and 10 int-1 risk, according to the International Prognosis Scoring System (IPSS), and assesses their survival and correlates thereof. For log-rank survival analysis, events were censored at the later of last dose, last visit, or last follow-up date. Results: Efficacy and safety findings of the parent trial have been published (Verstovsek S. N Engl J Med 363:1117, 2010): ruxolitinib treatment led to a rapid and sustained reduction in splenomegaly and improvements in MF symptoms; anemia and thrombocytopenia were the most common adverse events. After a median follow-up of 32 months, 58 of 107 pts (54%) were still receiving therapy. The corresponding overall survival (OS) was 69% (33 pts died, none due to therapy-related reasons: 14 while on therapy/within 30 days (d) of discontinuation (dc), and 19 off-study). Accounting for deaths occurring on the study, the 2-yr actuarial survival of int-2 and high-risk pts was 92% and 88%, respectively. However, the 2-yr survival of 13 int-2 and 21 high-risk pts who had discontinued therapy and were subsequently followed was 32% and 21%, respectively. MF transformed to acute leukemia in 9 pts: 5 while on therapy/within 30 d of dc, and 4 off-study; the transformation rate was 0.036/pt years. Pts with normal baseline cytogenetics did not have better survival than those with aberrations (Hazard ratio [HR]=1.52; p=0.24). However, pts with a baseline bone marrow fibrosis score of 2 had greater survival than those with a score of 3 (HR=2.21; p=0.031). Other evaluable baseline pt characteristics (gender, age, anemia, WBC and splenomegaly, did not affect survival. Surprisingly, high-risk pts (per either IPSS or dynamic IPSS [DIPSS] ) did not have significantly worse survival than int-2 pts. Importantly, reduction in palpable spleen length while on ruxolitinib was noted to be the most robust predictor for survival: pts who had a ≥50% reduction in spleen size (n=62) had significantly prolonged survival vs. those with a 〈 25% reduction (n=20) (Fig. 1; HR=4.94; p 〈 0.0001). Conclusions: Most MDACC pts with advanced MF in the phase I/II ruxolitinib study are still receiving therapy, demonstrating an OS of 69% after a median of 32 months. The 2-yr survival of pts who remained on therapy was 3–4-fold greater than those who discontinued therapy. Among baseline pt characteristics, only a lower bone marrow fibrosis score correlated with better survival. Conversely, achievement of ≥50% reduction in spleen size while on ruxolitinib resulted in greater survival (vs. 〈 25% reduction). Our data suggest that the most important factors that influence survival of MF pts receiving ruxolitinib are continuous active therapy and a degree of the spleen response, not pt pretherapy characteristics. Disclosures: Verstovsek: Incyte Corporation: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.3851.3851
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 3
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    Adverse Prognosis Of Extramedullary Disease In Patients With Chronic Myeloid Leukemia (CML) In The Tyrosine Kinase Inhibitor (TKI) Era: a Cohort Study Of 283 Blastic Phase CML Patients
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 2724-2724
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2724-2724
    Abstract: With the advent of tyrosine kinase inhibitors (TKIs), significant improvement has been made in the survival outcome of chronic myeloid leukemia (CML) patients. However, blastic phase (BP) CML remains a therapeutic challenge. Extramedullary disease (EMD) is a diagnostic criterion for BP, and patients with this presentation represent a unique subgroup of BP CML. The characteristics of EMD in BP CML patients have not been well described, especially in the era of TKIs. Methods We have analyzed CML patients with extramedullary BP either at the time of diagnosis or progressing from CP/AP from 2000 to 2011 and treated with different TKIs such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib at a single institution. All demographic, clinicopathologic variables and medication data including TKIs were collected at the time of the diagnosis of BP. Primary outcomes, overall survival (OS) were defined as time from diagnosis of BP to death. Results Among a total of 284 BP CML patients, median age was 52.6 (range: 15-81) years. Males were 65.0%. 72.2% were in myeloid BP versus 27.7% in lymphoid BP. Median follow up was 1.5 (range: 0.01-12) years. Median time from diagnosis of CML to BP was 2.3 (range: 0.01-28) years. 128 (45%) patients have died. Cytogenetic analysis at diagnosis demonstrated that 34% had only Philadelphia chromosome (Ph) present while 66% had other chromosomal abnormalities besides Ph. Trisomy 8 was the most common additional chromosomal abnormality (18%). 280 (99%) were treated with TKIs. Among them, 176 (623%) were treated with TKI monotherapy, and the rest with a combination of TKI and conventional chemotherapy. Among the patients treated with TKI, 134 (48%) used imatinib; 85 (30%), dasatinib; 48 (17%), nilotinib; 7 (3%), bosutinib; and 6 (2%), ponatinib. EMD was diagnosed in 78 patients (28%) of all BP CML patients. Patients with EMD had a median age of 52.8 (range: 19-80) while BP patients without EMD had a median age of 52.2 (range: 15-81). There were no statistically significant differences in age, gender, ethnicity, or time from diagnosis of CML to BP between EMD and non-EMD patients. Among patients with EMD 76% were myeloid, and 23% lymphoid compared with 70% myeloid and 30% lymphoid in patients without EMD (p=0.3). Patient with EMD had more Ph-only disease compared with patients without EMD (41% vs. 28%, p=0.03). Among 28 patients with deletion 7 chromosomal abnormality, only 1 patient had EMD (EMD vs. non-EMD chi-square p=0.002). There was no association between the presence of EMD and other chromosomal abnormalities such as double Ph, isochromsome 17, trisomy 8, deletion Y and variant Ph. Among patients with EMD, 39 (50%) had EMD in CNS; 22 (28%) in soft tissue, skin, or lymph nodes; 9 (12%) in bones; 8 (10%) in lung or pleura; and 4 (5%) in GI tract and liver. Among patient with BP CML, there were no statistically significant differences between the EMD and non-EMD groups in both complete hematologic response (CHR) rate and complete cytogenetic response (CCyR) rate at 3 months after the initiation of therapy (CHR: EMD 18% vs. non-EMD 22%, p=0.4; CCyR: EMD 8% vs. non-EMD 15%, p=0.1). However, the presence of EMD was associated with worse survival outcome (Hazard Ratio [HR]=1.62, Confidence Interval [CI] = 1.13-2.32, p=0.008). Median overall survival in patients with EMD was 0.8 versus 2.5 years in patients without EMD (log-rank test p=0.008, Figure 1). EMD in CNS was not associated with survival (HR=0.87, CI=0.50-1.51, p=0.6). In multivariate analysis controlling for age, gender, ethnicity, white cell counts, cytogenetics (presence of additional chromosomal abnormality), and pathology (myeloid versus lymphoid), EMD was still linked with adverse survival (adjusted HR=1.53, CI=1.04-2.26, p=0.03). Conclusion BP CML patients presenting with EMD are likely to have less additional chromosomal abnormality and have inferior overall survival compared with those without EMD. EMD may represent more aggressive pathophysiology in BP CML and may require more intensive treatment. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.2724.2724
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 4
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    Phase II Study Of The Hyper-CVAD Regimen In Combination With Ofatumumab As Frontline Therapy For Adults With CD-20 Positive Acute Lymphoblastic Leukemia (ALL)
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 2664-2664
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2664-2664
    Abstract: The hyper-CVAD regimen is an effective frontline program for de novo adult ALL. Expression of CD20 was identified as an adverse prognostic factor, associated with a higher incidence of relapse, lower 3-year complete remission duration (CRD) and lower 3-year overall survival (OS) rate. The addition of rituximab to the hyper-CVAD program in patients with CD20-positive ALL (≥20% expression by multicolor flow cytometry - FCI) improved outcome with 3-year CRD and OS rates by 68% and 65%, respectively. Ofatumumab (HuMax-CD20) targets a membrane proximal small-loop epitope on the CD20 molecule and was found to be more potent than rituximab in promoting complement-dependent cytotoxicity in vitro. Ofatumumab’s safety and efficacy has been proven in chronic lymphocytic leukemia. Therefore a combination of the hyper-CVAD regimen and ofatumumab may be associated with better response rates, higher 3-year complete remission duration (CRD) and overall survival rates. Methods In this phase II trial, pts with newly diagnosed ALL and pts who received one prior course of chemotherapy received 4 courses of hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone; the odd courses 1, 3, 5, 7); ofatumumab was given on courses 1 and 3, and 4 courses of MTX-Ara-C (methotrexate-cytarabine; the even courses 2, 4, 6, 8); ofatumumab was given on courses 2 and 4. This treatment will be followed by POMP (6-mercaptopurine, MTX, VCR, prednisone) maintenance therapy for approximately 30 months, interrupted by intensifications months 6, 7 and 18, 19 with MTX/Pegylated asparaginase and hyper-CVAD-ofatumumab. Central nervous system prophylaxis with MTX and ara-C was administered. When indicated local radiotherapy was administered in patients with bulky mediastinal disease Results To date 17 pts with de novo ALL and 2 pts in complete remission (CR) previously treated (1 with prior cycle of hyper-CVAD and 1 post fludarabine-cytarabine based regimen) have received a median of 5 cycles (1-8) of therapy; 3 pts did not receive the full 8 planned courses of induction-consolidation. 8 pts are receiving maintenance in CR. Median age is 50 years (39–71). Median WBC at diagnosis was 5.5 x 109/L (1 -189 x 109/L). CD20 expression above 20% was found in 11 pts (58%), between 10 and 20% in 1 (5%) and below 10% in 7 (37%). 2 pts (11%) had concomitant CNS disease at diagnosis. Among the 15 pts with evaluable baseline cytogenetic analysis, 10 (67%) were abnormal. All but one pt (94%) achieved a CR after cycle 1; 1 pt died of septic shock and multiple organ failure at day 21 of cycle 1. All eighteen (100%) pts achieved minimal residual disease (MRD) negativity as assessed by FCI; of whom 12 (67%) achieved MRD negativity after induction. Median time to neutrophil and platelet recovery for cycle 1 was 19 and 23 days, and 16 and 22 days for subsequent cycles, respectively. Grade ≥ 3 toxicity included increase of LFT’s in 7 pts (37%), increase of bilirubin in 5(26%), thrombotic events in 1 (5%) and neuropathy in 1 (5%). Febrile neutropenia episodes during induction and consolidation cycles were reported at rates of 76% and 65%, respectively. With a median follow up of 8 months (1-23), 18 pts are alive and in CR; 1 pt has undergone an allogeneic stem cell transplant after cycle 3 by reason of a highly complex karyotype at diagnosis. The 1-year CRD and overall survival rates were 100% and 95% respectively. Conclusion The combination of hyper-CVAD with ofatumumab is safe and highly effective in pts with CD20-positive ALL. Disclosures: Jabbour: GSK: Research Funding. Off Label Use: Ofatumumab in ALL. Faderl:Sanofi-Aventis: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Ravandi:Sunesis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Teva: Consultancy, Honoraria; Pfizer: Honoraria; Merck: Research Funding; Bayer/Onyx: Consultancy, Honoraria; EMD Serono: Research Funding; Medimmune: Research Funding; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.2664.2664
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 5
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    Low-Dose Hypomethylating Agents (HMAs) Are Effective in Patients (Pts) with Low- or Intermediate-1-Risk Myelodysplastic Syndrome (MDS): A Report on Behalf of the MDS Clinical Research Consortium
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 94-94
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 94-94
    Abstract: Background: HMAs improve survival of pts with higher-risk MDS; however, the role of HMAs is less clear in pts with lower-risk MDS. These pts have a heterogeneous prognosis, and some may benefit from early HMA therapy. To test the hypothesis that low-dose HMA therapy would be safe and effective in pts with lower-risk MDS, we treated pts with International Prognostic Scoring System (IPSS) low- or intermediate-1-risk MDS with low-dose HMA regimens using 3 days of either 5-azacytidine (AZA) or decitabine (DAC). Methods: Adult pts with de novo or secondary low- or intermediate-1-risk MDS, CMML or MDS/MPN were eligible for this study. Pts were treated with AZA 75 mg/m2 IV/SC daily or DAC 20 mg/m2 IV daily for 3 consecutive days on a 28-day cycle. The primary efficacy outcome was the overall improvement rate (OIR) defined as the composite of complete remission (CR), CR with insufficient hematologic recovery (CRi) and hematologic improvement (HI). Secondary outcomes included safety profile, duration of response, conversion to transfusion independence, event-free survival (EFS), and overall survival (OS). EFS was defined as the time to HMA failure, progressive disease, transformation to acute myelogenous leukemia (AML) or death from any cause. Chi-square test was performed to evaluate differences in response rates. EFS and OS were calculated using Kaplan-Meier estimates and compared using the log-rank test. Results: Between 11/2012 and 6/2015, 88 pts with lower-risk MDS were treated; 83 of them are currently evaluable for response assessment (65 MDS, 15 CMML and 3 MDS/MPN). Thirty pts received AZA (36%) and 53 pts (64%) received DAC. Median time from diagnosis to treatment was 5 weeks (range 1-272 weeks). Median age was 71 years (range 44-85 years). Sixteen pts (19%) had therapy-related MDS. Thirty-eight pts (46%) were transfusion-dependent for RBCs and/or platelets at baseline, and 17 pts (20%) had received prior growth factor support with erythropoietin-stimulating agents or G-CSF. By IPSS, 13 pts (16%) had low-risk and 70 pts (84%) had intermediate-1-risk disease. By the MDACC lower-risk scoring system, 38 pts (46%) had high-risk, 38 pts (46%) had intermediate-risk and 7 pts (8%) had low-risk disease. Twenty-seven pts (33%) had ≥5% bone marrow blasts. By IPSS, cytogenetics were good-risk in 55 pts (66%), intermediate-risk in 20 pts (24%) and poor-risk in 8 pts (10%). Mutation analysis was performed in 76 pts at the time of enrollment, 43 (57%) of whom had at least one molecular mutation. TET2 mutation was identified in 17 pts (22%), RUNX1 in 8 pts (11%), TP53 in 6 pts (8%), ASXL1 in 5 pts (7%), IDH1/2 in 5 pts (7%) and DNMT3A in 4 pts (5%). The median follow-up was 13 months (range 2-30 months) and median number of cycles received was 9 (range 2-29 cycles). The OIR for the entire cohort was 61%; 32 pts (39%) achieved CR, 11 (13%) achieved CRi and 8 (10%) achieved HI. Of the 38 transfusion-dependent pts at baseline, 9 (24%) became transfusion-independent. The median time to best response was 2.2 months (range 0.8 to 19.6 months). Median duration of response has not been reached with 71% of responders still on study. Low-dose HMA therapy was well-tolerated with only 6 pts (7%) requiring dose reduction and 19 pts (23%) requiring dose delay. AML developed in 4 pts (5%), and 17 pts (20%) have died. For the entire cohort, the 1-year EFS rate was 67%, and the 1-year OS rate was 86%. The median EFS and OS have not been reached. When stratified by IPSS and the MDACC lower-risk scoring systems, there was not a significant difference in OIR, EFS or OS among various risk groups (Table 1). Conclusions: Among pts with low- and intermediate-1-risk MDS, low-dose HMA therapy was well-tolerated and resulted in an OIR of 61%. Response rates, EFS and OS did not differ when pts were stratified by IPSS or the MDACC lower-risk scoring system. A randomized trial of low-dose AZA vs. DAC vs. best supportive care in lower-risk MDS is ongoing. Table 1. Response and survival rates by risk stratification Risk Stratification Risk Group N OIR (%) P (OIR) 1-year EFS rate (%) P (EFS) 1-year survival rate (%) P (OS) IPSS Low 13 54 0.540 83 0.751 86 0.295 Intermediate-1 70 63 65 85 MDACC Lower-Risk Scoring System Low 7 71 0.851 67 0.925 100 0.179 Intermediate 38 61 77 92 High 38 61 58 78 All Patients 83 61 67 86 Disclosures Sekeres: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Steensma:Incyte: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Onconova: Consultancy. DiNardo:Novartis: Research Funding. Estrov:incyte: Consultancy, Research Funding. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Verstovsek:Incyte Corporation: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.94.94
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    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 6
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    Inotuzumab Ozogamicin in Combination with Low-Intensity Chemotherapy (mini-hyper-CVD) As Salvage Therapy for Adult Patients with Refractory/Relapse (R/R) Acute Lymphoblastic Leukemia (ALL)
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 964-964
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 964-964
    Abstract: Background: Outcome of pts with R/R ALL is poor. Addition of IO to effective low-intensity chemotherapy might improve outcome. CD22 expression occurs in 〉 90% of pts with ALL. Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody bound to a toxin, calecheamicin, and has shown single-agent activity in relapsed/refractory ALL with a response rate of 58% and median survival of 6.3 months. The addition of targeted non-myelosuppressive therapy to effective low-intensity chemotherapy might further improve outcome. Methods: Pts ≥18 years with R/R ALL were eligible. The chemotherapy was lower intensity than conventional hyper-CVAD and referred to as mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses). Rituximab and intrathecal chemotherapy were given for first 4 courses. IO was given on Day 3 of each of the first 4 courses. Pts received IO at 1.8 mg/m2 for cycle 1 followed by 1.3 mg/m2 for subsequent cycles. Results: Thirty-five pts (14 men, 21 women) have been treated so far. Pts characteristics and outcome are summarized in Table 1. Median age is 35 yrs (range 9-87). Median follow-up is 10 months (mos). The overall response rate was 71%: 18 (51%) CR, 6 (17%) CRp, and 1 (3%) marrow CR. Four (11%) pts were refractory and early death was reported in 6 (17%) pts. Grade 3-4 non-hematological toxicities included infections, mucositis, increased LFTs, and VOD (1 on study who had prior allogeneic stem cell transplantation, 3 were post transplantation following IO therapy). Four (11%) pts were switched early to maintenance therapy due to poor functional status (n=1), infectious complications (n=2), and prolonged myelosuppression (n=1). Twelve (34%) pts proceeded to receive allogeneic stem cell transplantation; of the rest, 6 (17%) relapsed within 3 mos (range, 1 to 7). At the last follow-up, 17 pts (49%) are alive, 18 (51%) died: 6 early death (3 hemorrhage, 2 sepsis, and 1 unknown cause); 8 were responders (5 died post relapse after subsequent salvage, 2 died post transplantation VOD in 1, and 1 died due to sepsis and multiple organ failure), 4 were refractory and died of disease progression. The 6-month PFS and OS rates were 79% and 58%, respectively. Median survival for pts with CR/CRp/marrow CR was 14 mos versus less than 1 mo in pts with refractory disease. Furthermore, median survival was not reached in pts with S1, 4 mos in pts with S2 and 5 mos in pts with S3+. Conclusions: The combination of IO with low-intensity mini-hyper-CVD chemotherapy is effective and shows encouraging results (71% ORR) in pts with R/R ALL. Pts with previous liver damage and transplant candidate should be considered carefully for this treatment to minimize the risk of VOD.Table 1Patient characteristics and outcomeParameterCategoryN (%)/Median [Range]Follow-up (mos)10 [1-14] Age (yrs)35 [9-87]Performance Status (ECOG)0-130 (86)Salvage StatusS119 (54)S1, primary refractory4 (12)S1, CRD1 〈 12 mos8 (23)S1, CRD1 ≥12 mos7 (20)S28 (23)≥ S38 (23)KaryotypeDiploid8 (23)T(4;11)5 (14)Miscellaneous16 (46)Insufficient metaphases6 (17)CD2296 [29-100]CD20≥ 20%5 (14)CR18 (35)CRp6 (17)Marrow CR1 (3)No response4 (11)ORR25 (71)Early death6 (17)6-months PFS %79Median (months)Not reached6-month OS %58Median (months)7 Disclosures Kadia: GSK: Research Funding; ARIA: Honoraria. Kantarjian:ARIAD: Research Funding; Pfizer: Research Funding; Amgen: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.964.964
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    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 7
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    Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndromes (MDS) Who Have Relapsed or Are Refractory to Hypomethylating Agent (HMA) Therapy
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 534-534
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 534-534
    Abstract: Background: Treatment with HMAs such as azacitidine and decitabine has changed the overall outcome of patients with MDS. Failure to respond to or relapse from HMA treatment is associated with poor prognosis without further approved therapy. Clofarabine is a second-generation nucleoside analog with single-agent activity in MDS. Aim: This is a phase II trial to evaluate the safety and activity of the combination of clofarabine and low-dose cytarabine in the treatment of patients with high-risk MDS who failed prior HMA therapy. Materials and Methods: Eligible patients were adults older than 18 years with MDS who had no response, progressed, or relapsed following at least 4 cycles of therapy with either azacitidine and/or decitabine and an ECOG performance status of ≤ 2 at the time of study entry. Responses were defined according to IWG 2006 criteria. Induction therapy consisted of clofarabine 15 mg/m2 IV daily for 5 days (days 1-5) and cytarabine 20 mg SC twice daily for 7 days (days 1-7). Responding patients proceeded with consolidation therapy with clofarabine 15 mg/m2 IV daily for 3 days (days 1-3) and cytarabine 20 mg SC twice daily for 5 days (days 1-5) every 4 weeks for a maximum of 12 cycles. Overall survival (OS) was defined as the time between the date of the first dose of clofarabine and the date of death from any cause. Univariate (UVA) and multivariate analysis (MVA) related to response and survival were performed with Cox regression analysis. Results: Between January 2012 and December 2013, 56 patients were enrolled. Fifty-two patients were evaluable for response (4 patients had not been on-study long enough to evaluate). The median follow-up is 15.3 months (range, 1.2-27.7+), and the median age at enrollment was 71 years (31-83). Ten patients (19%) had prior chemotherapy and 12 (23%) had prior radiation therapy. Median bone marrow blast percentage was 15% (6-30%). Three patients (6%) had CMML-1, 4 (8%) had CMML-2, 7 (14%) had RAEB-1, 19 (37%) had RAEB-2, and 19 (37%) had RAEB-T. Eight (15%) patients had intermediate-1 risk, 23 (44%) had intermediate-2 risk, and 21 (40%) had poor risk by IPSS. By IPSS cytogenetic risk, 25 patients (48%) had low-risk cytogenetics, 15 (29%) had intermediate-risk, and 12 (23%) had high-risk. Mutational analysis detected 2 (4%) FLT3-ITD, 0 FLT3-D835, 7 (13%) RAS, 2 (4%) NPM1, and 2 (4%) JAK2 mutations. Thirty-nine patients (75%) received prior azacitidine therapy and 15 (29%) received prior decitabine therapy. The overall response rate (ORR) was 48% (9 [17%] achieved complete remission [CR] , 3 [6%] complete remission with incomplete platelet recovery [CRp] , 7 [13%] marrow CR, and 6 [12%] had stable disease with hematological improvement), and median duration of response was 12.0 months (range, 2.0-26.7+). Five patients (10%) went on to receive allogeneic stem cell transplantation. Of the 25 patients with low-risk cytogenetics, 16 (64%) achieved OIR, 5 (20%) CR, 3 (12%) CRp, 6 (24%) mCR, and 2 (8%) HI. Of the 15 patients with intermediate-risk cytogenetics, 5 (33%) had OIR, 4 (27%) CR, and 1 (4%) mCR. Of 12 patients with high-risk cytogenetics, 2 (17%) had OIR, 1 (8%), CR, and 1 (8%) HI. Median OS was 6.8 months (range, 0.4-27.7+). The median OS in patients with response and those without response was 〉 12.4 months (range, 3.5-27.7+) and 3.4 months (range, 0.4-16.1), respectively. Most toxicities were of grade ≤ 2 and included elevated liver enzymes in 41% of patients, elevated bilirubin in 38%, rash in 28%, nausea in 31%, headache in 24%, and febrile neutropenia in 28%. Grade ≥ 3 toxicities included elevated liver enzymes (3%) and elevated bilirubin (3%). 21 (40%) patients had clofarabine dose reduction after a median of 2 courses (range, 1-8). UVA and MVA for survival identified performance status ≥2 (p=0.002; HR, 4.860; 95%CI, 1.784-13.244), stable disease or progressive disease after clofarabine (p 〈 0.001; HR, 8.372; 95%CI, 3.233-21.677), thrombocytopenia 〈 30 (/109L) (p=0.001; HR, 3.659; 95%CI 1.682-7.958), and complex cytogenetics (UVA, p 〈 0.001; MVA, p= 0.110, HR, 2.329; 95%CI 0.826-6.564) as prognostic factors for poorer OS. Conclusion: The combination of clofarabine and low-dose cytarabine has an ORR of 48% in patients with MDS who failed prior therapy with HMA. The study continues to accrue, and updated results with longer follow up will be presented at the meeting. Disclosures Daver: Novartis: Research Funding. Kadia:GSK: Research Funding; ARIAD: Honoraria. Borthakur:Tetralogic Pharmaceuticals: Research Funding. O'Brien:Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding. Kantarjian:ARIAD: Research Funding; Pfizer: Research Funding; Amgen: Research Funding. Garcia-Manero:Epizyme, Inc: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.534.534
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
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  • 8
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    Phase I/II Study of Vosaroxin and Decitabine in Newly Diagnosed Older Patients (pts) with Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 461-461
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 461-461
    Abstract: Background: Vosaroxin, is a first-in-class anti-cancer quinolone derived (AQD) DNA intercalator and topoisomerase II inhibitor, which is not a substrate for p53 or P-glycoprotein, and is currently under evaluation for the treatment of pts with AML and high-risk MDS. Methods: Pts are eligible if they have AML or high-risk MDS (defined as having 〉 /= 10% blasts), are 60 years of age or older, and have adequate performance status (ECOG 〈 /= 2) and organ function. In the phase I part of the study the first six pts received vosaroxin 90 mg/m2 daily on days 1 and 4 with decitabine 20 mg/m2 daily for 5 days repeated in approximately 4 to 5 week intervals for up to 7 cycles. This dose was well tolerated in the 6 patients. However, due to occurrence of 8 episodes of grade 3/4 mucositis in 7 of the subsequent 16 patients the induction dose of vosaroxin was reduced to 70 mg/m2 with the vosaroxin dose maintained at 70 mg/m2 or reduced to 50 mg/m2 in consolidation cycles. 34 patients were treated at this modified dose regimen. The primary endpoint was to determine the overall response rate including complete response (CR) + CR without platelet recovery (CRp) + CR with insufficient hematological recovery (CRi). Secondary endpoints were: CR duration, disease-free survival, overall survival, safety, and early mortality. Results: To date, 56 pts (50 AML, 6 high-risk MDS) with a median age of 69 years (range, 60 - 78) have been enrolled. They included 19 (34%) pts with diploid cytogenetics, 21 (38%) with complex cytogenetic abnormalities including chromosome 5 and/or 7 abnormalities, and 16 (28%) with other miscellaneous abnormalities. Fourteen (25%) pts with AML had antecedent hematological disorders (AHD) including 7 with MDS, 4 with MPN, 2 with MDS/MPN, and 1 with CLL. Four pts with AHD had received prior therapy including 5-azacytidine (n=1), decitabine (n=1), ruxolitinib + 5-azacytidine (n=1), and lenalidomide (n=1). Additionally, 10 (18%) pts had therapy-related disease with prior exposure to chemotherapy or radiation therapy. Median bone marrow blast %, and median white blood cell, hemoglobin, & platelet counts were 40% (range, 11 - 97), 3.4 x 109/L (range, 0.4 - 57), 9.4 g/dL (range, 6.8 - 13.1), and 35 x 109/L (range, 7 - 333), respectively. All 56 pts have completed 〉 /=2 cycles of therapy and were evaluable for response; 30 (54%) achieved CR, 8 (14%) CRp, and 5 (9%) CRi for an overall response rate of 77%. Minimal residual disease (MRD) by 19 color flow-cytometry was evaluable in 35 of the 43 responders. MRD was not detectable in 24 of 35 (66%) evaluable responders. All 56 patients had baseline cytogenetics and clinically validated next generation sequencing-based analysis for the detection of somatic mutations in the coding sequence of 28 genes commonly mutated in myeloid neoplasms. Response by baseline characteristics is shown in table 1. The median number of cycles to response was 1 (1 - 4); 13 pts have required 〉 1 cycle to achieve response. Seven (13%) pts have proceeded to allogeneic stem cell transplant. The median follow-up is 4.7 months (1.3 - 20.8). The regimen was well tolerated with the main therapy related grade 〉 /= 3 toxicities were mucositis in 10 (18%) pts and liver enzyme elevation in 8 (14%). The median overall survival (OS) for all pts is 8.3 months. Four-week and 8-week mortality for all pts were 0 and 14%, respectively. The induction dose of vosaroxin was 90 mg/m2 in 22 pts and 70 mg/m2 in 34 pts. The lower induction dose of vosaroxin was associated with a reduced early mortality and an improved overall response rate and OS (Table 2 and Figure 1). Conclusion: Combination of vosaroxin and decitabine is effective in older pts with AML and high-risk MDS. Reponses were encouraging in the pts with TP53 and complex cytogenetics. The lower dose of vosaroxin 70 mg/m2 on days 1 and 4 is better tolerated and is associated with significantly improved outcomes. Table 1. Response by baseline characteristics Parameter Category N Overall response(CR, CRp, CRi) CR Age 60-74 44 80% 57% 〉 /=75 12 67% 42% Cytogenetics Diploid 19 86% 57% -5/-7/other adverse 21 68% 42% Miscellaneous 16 75% 63% MutationStatus IDH2 11 91% 73% IDH1 14 57% 43% TP53 11 73% 55% RAS 11 64% 28% Table 2. Outcomes by induction dose of vosaroxin Induction dose(vosaroxin) N Med OS 8-week mortality Overall Response CR Need 〉 1 cycle to response 90 mg/m2 22 5.5 mos 25% 73% 41% 23% 70 mg/m2 34 11.5 mos 6% 79% 62% 23% Figure 1. OS by induction dose of vosaroxin Figure 1. OS by induction dose of vosaroxin Disclosures Daver: ImmunoGen: Other: clinical trial, Research Funding. Off Label Use: Vosaroxin in the management of AML. Pemmaraju:Stemline: Research Funding; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; LFB: Consultancy, Honoraria. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding. DiNardo:Novartis: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Teva: Research Funding; BerGenBio AS: Research Funding; BMS: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Craig:Sunesis: Employment, Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.461.461
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 9
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    Incidence of Central Nervous System (CNS) Relapse in De Novo Adult Acute Lymphoblastic Leukemia (ALL)
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 940-940
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 940-940
    Abstract: In the era of improved outcomes with systemic chemotherapy for de novo adult ALL, prevention of CNS relapse becomes even more paramount. Isolated CNS relapse may herald eventual marrow relapse in the absence of definitive CNS-directed and systemic chemotherapy strategies. CNS prophylaxis can be successfully achieved with intrathecal chemotherapy treatments (IT) in conjunction with systemic chemotherapy inclusive of high-dose methotrexate (MTX) and/or high-dose cytarabine (ara-C) without use of radiation therapy (XRT). The hyper-CVAD regimen (cycles of fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with cycles of high dose MTX (1 g/m2) and cytarabine (3 gm/m2; 1 gm/m2 for age 〉 60 yrs) incorporates IT MTX alternating with IT ara-C during the intensive phase of induction-consolidation. The number of IT treatments was determined by CNS risk (4 IT for low risk = LDH 〈 1400 U/L and low proliferative index; 16 IT for high risk = LDH 〉 1400 U/L or high proliferative index; 8 IT for indeterminate risk = one of parameters unknown). An analysis performed in 2000 (Kantarjian et al, J Clin Oncol 18: 547, 2000) identified CNS relapse rates of 6%, 2%, and 0% for the low, high, and indeterminate CNS risk groups, respectively. The number of IT administered was modified from 4 to 6, from 16 to 8, and maintained at 8 for these CNS risk groups, respectively, until 2010, at which point all pts received 8 IT. An analysis was conducted to examine the incidence of CNS relapse for 565 pts with de novo ALL treated with hyper-CVAD-based regimens (n=453, inclusive of nelarabine, monoclonal antibodies such as rituximab, ofatumumab or inotuzumab, and/or tyrosine kinase inhibitors such as imatinib, dasatinib or ponatinib) from 2001 to 2014 or with the augmented BFM regimen (one IT ara-C, 15 IT MTX, Capizzi methotrexate) (n=112) from 2006 to 2014. T-lymphoblastic lymphoma (designated for 8 IT) and Burkitt leukemia/lymphoma (designated for 16 IT) cases were excluded from the analysis. The incidence of CNS relapse (n=42) was 7% overall; 59% were isolated CNS relapses (n=25, 5%) without concurrent marrow relapse. Median time to isolated CNS relapse was 19 mos versus 10 mos for concurrent relapse. The incidence of CNS relapse for cases with CNS disease at initial presentation (n=70) was 19%. Factors predictive of higher incidence of CNS relapse included younger age (12% for 30 yrs or younger, 3.5% for 60 yrs or older, p=.01), elevated LDH 〉 1400 U/L (13% vs 4%, p 〈 .001), and Philadelphia chromosome positivity (12% vs 6%, p=.05). The overall CNS relapse rates were 4% for the hyper-CVAD and monoclonal antibody regimens; 11% for the augmented BFM regimen, and 14%-15% for the hyper-CVAD and imatinib/dasatinib regimens. The CNS relapse rate declined from 10% for pts treated prior to 2010 to 8% thereafter (8 IT for all risk groups). Overall, the 3-yr survival rates for CNS relapse was 47% vs 63% without CNS relapse (p=0.006). Modifications to the hyper-CVAD and tyrosine kinase inhibitor regimens for Philadelphia positive ALL have been implemented to increase the number of IT from 8 to 12. Similar modifications will be implemented for the augmented BFM regimen with consideration for incorporation of high dose MTX. Additional analyses will further refine the CNS risk model in order to guide CNS prophylaxis. Alternative agents such as IT rituximab may improve outcomes for CD20 positive cases with CNS disease at presentation; a clinical trial in the setting of active CNS disease is underway. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.940.940
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 10
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    Myelodysplastic Syndrome with Fibrosis: Experience of a Single-Institution with 139 Patients.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 2775-2775
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2775-2775
    Abstract: Abstract 2775 Poster Board II-751 Background: A fraction of patients with MDS present with bone marrow fibrosis in addition to dysplastic hematopoiesis. It is believed that MDS patients who present with fibrotic features in the bone marrow constitute a group with worse survival. Aims: To describe clinical features and survival outcomes of patients with a diagnosis of MDS with myelofibrosis treated at the M.D. Anderson Cancer Center. Methods: We carried out a retrospective review of patients who had a diagnosis of MDS in the presence of grade 2+ or greater fibrosis. Relevant clinical data at presentation was reviewed. Survival was estimated by Kaplan-Meier method. Results: From 1997 until 2008, 129 patients with a diagnosis of MDS with myelofibrosis and 10 patients with chronic myelomonocytic leukemia (CMML) and myelofibrosis were seen at our institution. Median age was 64 years (range 27–85). Subclassification by the World Health Organization criteria included refractory anemia (N=16, 12%), refractory anemia with ringed sideroblasts (N=4, 3%), refractory cytopenias with multilineage dysplasia (N=16, 12%), refractory anemia with excess blasts (RAEB; N=62, 45%), 5q- syndrome (N=2, 1%) and therapy-related MDS (t-MDS; N=29, 21%). Marrow reticulin fibrosis was graded in 115 patients, being grade 2 in 34 patients (30%), grade 3 in 40 patients (35%) and grade 4 in 41 patients (35%). Splenomegaly was present in 16 patients (12%), being more common in patients with a morphological diagnosis of CMML (9% vs 50%, p=0.001), and the median spleen size below the left costal margin was 8 cm (range 2–10). The median white blood cell count at diagnosis was 3.6×109/L (0.6–60.7), hemoglobin 9.6 g/dL (5.1–14.4) and platelet count 53×109/L (6–1195). Median lactate dehydrogenase level was 621 IU/L (range 263–4037). The median bone marrow blasts percentage was 4% (0–19%). Cytogenetic analysis was available in 127 (91%) cases, and was abnormal in 63 (50%) patients. The most common abnormalities were: complex karyotype in 35 patients (28%), −7/del(7q) in 7 patients (6%), del(20q) in 6 patients (5%), −5/del(5q) and trisomy 8 in 4 patients (3%) each. Analysis of the JAK2V617F mutation was done in 30 patients, being positive in 6 (20%; RAEB=3, t-MDS, CMML and 5q− syndrome in one each). One additional patient with RAEB was positive for the MPLW515K mutation. After excluding patients with CMML and t-MDS, the International Prognostic Scoring System (IPSS) score was available in 92 patients. IPSS scores were distributed as follows: low (N=15; 16%); intermediate-1 (N=47; 51%); intermediate-2 (N=25; 27%) and high (N=5; 6%). Median transformation-free survival (TFS) was 16 months (range 0–127) and median overall survival (OS) was 20 months (range 0–130) for the whole cohort. There was no difference in OS (p=0.18) or TFS (p=0.24) by degree of fibrosis. OS was influenced by the IPSS score, median OS being 38, 21, 11 and 5 months for patients with Low, Int-1, Int-2 and High risk scores, respectively (p=0.01). Similarly, median TFS was 29, 18, 10 and 5 months for patients with Low, Int-1, Int-2 and High risk scores (p=0.007). For patients with t-MDS, median TFS and OS were 15 months both, not different from patients without previous history of chemotherapy and/or radiation therapy (p=0.84 and p=0.73, respectively). Conclusion: In our cohort of patients with a diagnosis of MDS with myelofibrosis, we found a higher prevalence of JAK2 mutations and splenomegaly than previously reported. More detailed mutation analysis is in progress. The degree of fibrosis did not influence survival in our patients. The median OS and TFS for patients with Low/Int-1 risk is inferior to that reported in the literature for patients with MDS without fibrosis with similar risk. Thus, early treatment strategies should be considered for patients with MDS who present with fibrotic features in the bone marrow. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.2775.2775
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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