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  • 1
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    Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission
    Elsevier BV ; 2016
    In:  Biology of Blood and Marrow Transplantation Vol. 22, No. 2 ( 2016-02), p. 380-385
    Details
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 22, No. 2 ( 2016-02), p. 380-385
    Type of Medium: Online Resource
    ISSN: 1083-8791
    URL: Article
    DOI: 10.1016/j.bbmt.2015.08.035
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
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  • 2
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    Specific Features Identify Patients with Relapsed or Refractory Mantle Cell Lymphoma Benefitting from Autologous Hematopoietic Cell Transplantation
    Elsevier BV ; 2013
    In:  Biology of Blood and Marrow Transplantation Vol. 19, No. 9 ( 2013-09), p. 1403-1406
    Details
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 19, No. 9 ( 2013-09), p. 1403-1406
    Type of Medium: Online Resource
    ISSN: 1083-8791
    URL: Article
    DOI: 10.1016/j.bbmt.2013.07.005
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
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  • 3
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    Bendamustine (Treanda®)-Based Regimens Are Effective In Mobilizing Peripheral Blood Hematopoietic Stem Cells For Autologous Transplantation
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 2033-2033
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2033-2033
    Abstract: Background High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for patients with advanced or treatment refractory multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Stem cell proliferation and mobilization can be enhanced though the addition of myelosuppressive chemotherapy prior to GCSF administration. Chemotherapeutic agents without cross resistance to prior therapies may support peripheral blood stem cell (PBSC) collection and improve patient outcomes by exacting a more potent direct anti-tumor effect prior to ASCT. Bendamustine (Treanda®) is a synthetic chemotherapeutic agent that shares structural similarities to both purine analog and alkylating agents without significant cross resistance to other compounds in either drug class. Bendamustine appears to have low stem cell toxicity in vitro, is well tolerated, and has activity in MM and NHL, but the potential for the purine moiety to adversely impact stem cell reserve is unknown. We hypothesized that bendamustine’s activity in patients with disease resistant to first line therapies makes it a logical candidate for chemotherapy based PBSC mobilization and tested its impact on stem cell yield. Methods Patients were eligible if they had relapsed or refractory MM, B-cell NHL or T-cell NHL and were candidates for ASCT. Other criteria included: age 〉 18 years, ANC 〉 1,500/mm3, platelets 〉 100,000/mm3, adequate renal and hepatic function, 〈 3 prior myelotoxic regimens, 〈 6 cycles of lenalidomide, no failed mobilization attempt, and no prior pelvic/spinal irradiation. Patients received 1 cycle of BED therapy [bendamustine (120 mg/m2 IV d 1, 2 - provided along with financial support for this study by Teva Pharmaceuticals), etoposide (200 mg/m2 IV d 1- 3), dexamethasone (40 mg PO d 1- 4), delivered as an outpatient, followed by filgrastim (initially 10 mcg/kg/d sc; starting on d 5 through end of collection)]. Apheresis was initiated when peripheral blood CD34 cell counts were 〉 5/µL. The primary endpoint was successful mobilization, defined as collection of 〉 2.0 x 106CD34 cells/kg. AEs were graded using the CTCAE v4.0. Results Thirty-seven patients (32 MM, 4B-cell NHL, 1 NK/T-cell NHL) were treated. The median age was 60 years (range 43-70). The median number of prior therapies was 1 (range 1-3) for MM and 2 (range 1-3) for NHL patients. All patients (37/37) were successfully mobilized. The median number of CD34+ cells collected was 19.43 x 106/kg (range 4.35 to 55.51 x 106). All MM patients collected 〉 10 x 106 CD34+cells/kg. The median time from the start of BED mobilization therapy to the first day of CD34 stem cell collection was 12 days (range 9 to 20 days). The median number of apheresis days was 1 (range 1 to 4). A predictable pattern of leucocyte nadir and recovery was demonstrated (95% of patients started apheresis between days 9-13). Two patients (5%) were given plerixafor and for 2 patients (5%) GCSF was increased to 16 mcg/kg twice daily. Among the 37 patients mobilized and collected, 31 have thus far undergone ASCT and 100% (31/31) achieved an unsupported neutrophil count 〉 500/µL at a median of 15 days (range 7-19) after PBSC infusion and a platelet count 〉 20K/µL at a median of 11 days (range 8-14). Ten SAEs were observed in 8 patients and 1 patient died due to disease progression prior to ASCT. SAEs include: neutropenic fever (1, grade [GR] 3), bone pain (2, GR 3), renal insufficiency (1, GR 1), atrial fibrillation (1, GR 2), hypotension (1, GR 3), stroke (1, GR 2), and one patient accounted for 3 SAEs including GR 3 tumor lysis syndrome and sepsis and GR 5 disease progression. Among twenty-nine evaluable patients to date, responses include: CR= 4 PR=2, SD=19 and PD=4. The ORR to this single cycle of therapy was 21%. Conclusions PBSC mobilization with BED is safe and effective. BED is not an acute stem cell toxin. Large numbers of stem cells were rapidly mobilized and resulted in short durations of apheresis. No patient with MM collected 〈 10 x 106 CD34+ cells/kg (sufficient for 2 ASCTs). Twenty-one percent of patients demonstrated a measurable response to a single cycle of BED therapy and an additional 65% of patients had stable disease. In patients who were transplanted, the time to neutrophil and platelet engraftment was comparable to other chemotherapy based mobilization regimens. The BED regimen was well tolerated and these findings suggest that the role of BED in PBSC mobilization should be further explored. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.2033.2033
    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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    Failure of Intensified Induction Therapy and Inability to Undergo Stem Cell Transplantation Predict Dismal Outcomes in Relapsed/Refractory MYC+ B-Cell Lymphoma
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 1731-1731
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1731-1731
    Abstract: Background: Aggressive B-cell non-Hodgkin lymphomas (B-NHL) harboring MYC oncogene abnormalities carry a poor prognosis and frequently relapse after standard front-line therapy. However, little is known about the outcomes following these relapses. Multiple series have suggested that survival is very poor, but detailed descriptions are generally lacking. We sought to examine this under-described yet frequent scenario. Methods: We performed a retrospective analysis of our center’s experience under an IRB-approved protocol. Patients included those with MYC copy number alteration (CN) or gene rearrangement (GR) as detected by fluorescence in situ hybridization and/or metaphase cytogenetics that did not meet diagnostic criteria for Burkitt lymphoma and who experienced initial treatment failure (ITF): relapse after or unable to achieve complete remission (CR) following upfront therapy. Frequencies of characteristics between groups were compared using a chi-square test. Kaplan-Meier plots and Cox proportional hazard models were used to investigate associations between variables. Clinical follow-up was updated as of June 2014. Results: We identified 43 pts with relapsed/refractory B-NHL and a MYC gene abnormality, 31 (72%) of which were MYC GR. Of these 31, 18 (64%) were “double-hit” lymphomas with concurrent BCL2 GR, plus another 2 (7%) that also possessed BCL6 GR (“triple-hit”; BCL2/BCL6 data missing from 3). There were no significant differences in overall survival (OS) from ITF between MYC CN, MYC-only GR, and double-/triple-hit (p = 0.73). Additional clinical features at initial diagnosis included median age of 60 years (yrs) (range: 19-72 yrs), stage III-IV disease in 84% (n = 36), elevated LDH in 83% (n = 24; missing data from 14), and B symptoms in 42% (n = 18). Median time from diagnosis until ITF was 6 months (mo) (range: 1-41 mo). Median follow-up from ITF of surviving pts was 8 mo (range: 2-66 mo). Initial chemotherapy consisted of CHOP in 56% (n = 24), while 35% (n = 15) received a more intense regimen: hyperCVAD (n = 7), dose-adjusted EPOCH (n = 6), or CODOX-M/IVAC (n = 2); all but 1 pt received rituximab (R) with initial therapy. There was no significant difference in the use of CHOP vs intensified regimens with regard to the presence of MYC CN (33% vs 20%, respectively) or MYC GR (67% vs 80%, respectively; p = 0.37). However, 1-yr OS from ITF among those who received CHOP upfront was significantly higher than those who received intensified upfront therapy (34% vs 0%, p = 0.01; Figure 1). CHOP was used more frequently among those who later received ICE salvage (n = 21) than cytarabine (Ara-C)-based salvage (n = 10; 71% vs 40%, respectively; p = 0.09). The rates of subsequent stem cell transplantation (SCT) following ICE and Ara-C were comparable (57% vs 40%, respectively; p = 0.37). R was included in all but 1 pt who received Ara-C. Pts who received ICE had a significantly higher 1-yr OS from ITF than those treated with Ara-C (28% vs 8%, p = 0.01; not shown). 1-yr OS from ITF was significantly better among the 17 pts (40%) who were able to undergo autologous (auto) SCT than the 22 (51%) who did not (38% vs 7%, respectively; p = 0.02; Figure 2). Four pts (9%) received an allogeneic (allo) SCT for their initial salvage SCT and were analyzed separately: Three pts relapsed at 1, 4, and 8 mo post-SCT, while the fourth died in CR 3 yrs later. Rates of SCT use were comparable for pts who initially received CHOP (50%) and those treated with intensified initial therapy (60%; p = 0.54). All but 1 pt in this cohort were treated with the intent of undergoing SCT. Six pts (14%) had confirmed central nervous system (CNS) relapse, 1 of whom received CNS prophylaxis during initial therapy. Among these, 4 died within 6 mo of ITF and 1 was lost to follow-up with progressive disease only 2 mo after ITF. The remaining pt underwent auto SCT in CR and is alive but with only 1 mo of follow-up. Conclusions: We have described the outcomes of one of the largest cohorts of relapsed/refractory MYC+ B-NHL reported to date. Though intensified initial therapy may improve outcomes upfront, pts for whom these regimens fail do exceedingly poorly. Pts unable to undergo SCT also have exceptionally dismal outcomes. These subsets of pts in particular should be offered novel therapies in the context of clinical trials. Further, more aggressive initial therapies including consolidative SCT are worth studying since the outcomes after ITF are so poor. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Gopal: Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda/Millennium: Honoraria, Research Funding, Speakers Bureau; Gilead: Research Funding; Janssen: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Piramal: Research Funding; Teva: Research Funding; Spectrum: Research Funding; BioMarin: Research Funding; Merck: Research Funding; Emergent: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.1731.1731
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 5
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    High-dose CD20-targeted radioimmunotherapy-based autologous transplantation improves outcomes for persistent mantle cell lymphoma
    Wiley ; 2015
    In:  British Journal of Haematology Vol. 171, No. 5 ( 2015-12), p. 788-797
    Details
    In: British Journal of Haematology, Wiley, Vol. 171, No. 5 ( 2015-12), p. 788-797
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Article
    DOI: 10.1111/bjh.13773
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 2015
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  • 6
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    Long Term Follow-up of High-Dose CD20-Targeted Radioimmunotherapy-Based Autologous Transplantation for Patients with Mantle Cell Lymphoma
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 3967-3967
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3967-3967
    Abstract: Background: Autologous stem cell transplantation (ASCT) is commonly employed in the treatment of mantle cell lymphoma (MCL), though long-term remission following this intervention is relatively uncommon, particularly for patients with relapsed/refractory disease. We hypothesized that high-dose radioimmunotherapy-(RIT) based conditioning prior to ASCT could improve outcomes based on the radiosensitivity of MCL and reduced cross-resistance with chemotherapy. Methods: We evaluated the outcomes of patients with MCL treated with myeloablative conditioning using iodine-131 (131I) conjugated to the anti-CD20 antibody tositumomab with or without additional chemotherapy followed by ASCT on 4 sequential prospective clinical trials. These trials included single agent RIT, RIT + etoposide + cyclophosphamide, and RIT + fludarabine. We retrospectively identified a comparator group of patients at our institution undergoing ASCT for MCL without RIT, using conditioning regimens including carmustine, etoposide, cytarabine, and melphalan (BEAM); busulfan, melphalan, and thiotepa (BuMelT); and 12 Gy of total body irradiation (TBI) plus cyclophosphamide with or without etoposide. We described and compared the outcomes from each group including differences in event rates evaluated by the Cox proportional hazards regression model. To account for imbalanced covariates between subgroups, adjusted estimates of survival were generated (Storer, et al., Lifetime Data Anal, 2008, p. 484). Follow-up was updated as of October 2013. Results: From November 1995 to May 2011, 162 sequential MCL patients received high-dose therapy and ASCT at our center, including 61 (38%) who received RIT-based conditioning. RIT patients received a median of 19.8 GBq (534 mCi; range: 7.6-40.7 GBq [205-1100 mCi]) of 131I to deliver a median of 25 Gy (range: 20-27) absorbed dose to critical organs. Median follow-up from ASCT for all surviving patients was 5.1 yrs (range: 0.3-17.1). Patients treated with RIT-based ASCT were less likely to be in first remission (48% vs 72%; p = 0.002), be in complete remission (CR) at ASCT (26% vs 61%; p 〈 0.001), or have chemosensitive disease (84% vs 96%; p = 0.006) compared to controls. The 2-year, 5-year, and median PFS were 66%, 49%, and 64 months (respectively) for the control group compared to 70%, 45%, and 54 months (respectively) for the RIT group (p = 0.77; see Table). The 2-year, 5-year, and median OS were 76%, 64%, and 126 months (respectively) for the control group compared to 82%, 62%, and 80 months (respectively) for the RIT group (p = 0.75; see Table). Multivariate analysis (adjusting for chemosensitivity, remission status, ASCT in first remission, and age) indicated that RIT-based conditioning was associated with a reduced risk of mortality and treatment failure (i.e., death or relapse; see Table and Figure). Furthermore, the relative benefit of RIT increased with worsening pre-ASCT disease status (from CR to partial remission to stable/progressive disease), with HRs for mortality 1.1, 0.53, and 0.04, and HRs for treatment failure 1.2, 0.38, and 0.07 (respectively). Incidences were comparable between the RIT and control groups in terms of non-relapse mortality (NRM) (7% vs 8%, respectively) and secondary malignancies (9.8% vs 12%), including acute myeloid leukemia or myelodysplasia (4.9% vs 3%). Conclusions: RIT-based conditioning is associated with improved outcomes following ASCT for MCL after controlling for imbalances in important risk factors, with the greatest benefit among patients with more advanced disease. Rates of NRM and secondary malignancies were comparable with both approaches. These data support the further study of high-dose RIT in a risk-adapted approach to ASCT for MCL. Table: Univariate and multivariable comparison of high-dose RIT-based vs conventional ASCT. Comparison ASCT Conditioning Treatment Failure Overall Mortality HR (95% CI) P HR (95% CI) P Univariate Control 1 - 1 - RIT 1.01 (0.69-1.6) 0.77 1.1 (0.67-1.8) 0.75 Multivariable Control 1 - 1 - RIT 0.47 (0.27-0.79) 0.005 0.49 (0.28-0.86) 0.01 Figure: Estimated PFS after adjusting for chemosensitivity, remission status, ASCT in first remission, and age following high-dose RIT-based or conventional (Control) ASCT for MCL. Figure 1 Figure 1. Disclosures Off Label Use: 131I-tositumomab is not FDA approved for autologous stem cell transplant conditioning.. Gopal:Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Gilead: Research Funding; Spectrum: Research Funding; Teva: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.3967.3967
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 7
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    Rituximab Maintenance Therapy after Autologous Stem Cell Transplantation Improves Survival of Patients with Mantle Cell Lymphoma
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 3985-3985
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3985-3985
    Abstract: Background High dose therapy and autologous stem cell transplantation (ASCT) can improve outcomes for patients with mantle cell lymphoma (MCL), yet relapse ultimately occurs in the majority of patients. Maintenance rituximab (MR) administered after induction chemotherapy has been shown to improve overall survival (OS), but limited comparative data are available regarding the impact of MR following ASCT. We report the impact of MR on outcomes following ASCT in a large series of patients with MCL. Methods One hundred sixty four consecutive patients with MCL that underwent ASCT for MCL at our center between November 1995 and May 2011 were included in this retrospective analysis. Patients that received MR after ASCT were compared to patients that did not receive maintenance rituximab after ASCT (no-MR). Two patients underwent tandem autologous/allogeneic stem cell transplants and were excluded from analysis; inadequate follow-up data precluded the evaluation of MR administration in an additional 5 patients. MR was treated as a time-dependent covariate to account for the variability in the time to initiation after ASCT. Statistical significance of differences in event rates between the MR and no-MR groups was evaluated with the Cox proportional hazards regression model. Two-sided p-values less than 0.05 were considered statistically significant. Results A total of 157 patients met the above criteria and were evaluated in this study. MR was administered to 50 (32%) patients and the remaining 107 (68%) patients received no MR after ASCT. Median age at the time of ASCT was 58 (range 35–71). All patients in the MR group had received rituximab prior to ASCT, whereas 13 of the 107 patients in the no-MR group had no prior rituximab (p = 0.01). Patients in the MR group were more likely to have had chemo-sensitive disease (p = 0.05) and to have undergone ASCT during first remission (p = 0.0001) and in complete remission (CR) (p = 0.0003). Patients in the no-MR group were more likely to have received radio-immunotherapy based conditioning (p 〈 0.0001). The groups were well matched for simplified MIPI score (sMIPI) at the time of diagnosis (p = 0.50) and at ASCT (p = 0.88). A median of 8 (range 1 to 16) doses of MR was administered at a dose of 375 mg/m2. MR was initiated at a median of 77 days after ASCT (range 27 to 287) and the last dose was administered at a median of 271 days after ASCT (range 55 to 1074). The most common dosing schedules included weekly dosing for 4 weeks for two cycles separated by 6 months (n = 15), monthly dosing (n = 8), and every 3-month dosing (n = 7); a variety of dosing schedules were used in the remaining cases (n = 20). Grade 4 neutropenia was observed in 16 of 47 evaluable patients (34%) in the MR group, and 16 of 87 evaluable patients (18%) in the no-MR group (p = 0.04). Granulocyte colony stimulating factor (GCSF) was administered for neutropenia in 15 of 47 evaluable patients (32%) in the MR group, and 10 of 85 evaluable patients (12%) in the no-MR group (p = 0.005). MR was associated with a significantly prolonged PFS (HR 0.33, p = 0.0005) and OS (HR 0.40, p = 0.01) following a multivariate adjustment (Table 1) with a median follow up of 4.75 years. Likewise, in a landmark analysis limited to patients alive and without progression at day 100 after ASCT (n = 147), 3-year PFS and OS were 78% and 86%, respectively, in the MR group and 59% and 71%, respectively, in the no-MR group (Figure 1). Conclusion These data suggest that MR administered following ASCT improves both PFS and OS for patients with MCL with an associated increase in the risk of severe neutropenia and consequent use of GCSF. Randomized, prospective trials are needed to confirm these findings and establish post-ASCT MR as standard of care in treating MCL. Table 1. Multivariate Cox proportional hazards modeling using maintenance rituximab as a time-dependent covariate Progression Free Survival1 Overall Survival2 HR p-value HR p-value Maintenance rituximab 0.33 (0.18 – 0.62) 0.0005 0.40 (0.20 – 0.81) 0.01 1Adjusted for: Age, B-symptoms, MIPI at time of ASCT, disease status at ASCT, chemo-sensitivity, ASCT in first remission, conditioning regimen 2Adjusted for: Age, disease status at ASCT, chemo-sensitivity, ASCT in first remission, conditioning regimen Figure 1. Kaplan-Meier plots using landmark of day 100 after ASCT for (A) progression free survival and (B) overall survival Figure 1. Kaplan-Meier plots using landmark of day 100 after ASCT for (A) progression free survival and (B) overall survival Disclosures Off Label Use: Rituximab as maintenance therapy after autologous stem cell transplantation for mantle cell lymphoma.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.3985.3985
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 8
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    The Pre-Transplant Mantle Cell Lymphoma International Prognostic Index Predicts Overall and Progression-Free Survival Following High-Dose Therapy and Autologus Stem Cell Transplant for Mantle Cell Lymphoma
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 2026-2026
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2026-2026
    Abstract: Abstract 2026 Background: High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is frequently employed to improve outcomes in patients with mantle cell lymphoma (MCL), yet results after transplant vary widely. We and others have shown that the Mantle Cell International Prognostic Index (MIPI) measured at diagnosis can predict overall survival (OS) after HDT and ASCT (Geisler, Blood 2010; Budde JCO 2011). Unfortunately, this approach is often limited at the time of transplant by the lack of available MIPI data from the time of diagnosis. Furthermore, the MIPI at diagnosis does not take into account other disease-related data that may be present at transplant. We hypothesized that the MIPI measured immediately before initiation of HDT could be attainable and predictive of outcomes after ASCT and explored the contribution of this measure along with other clinical factors to OS and progression-free survival (PFS). Methods: Records of consecutive MCL patients undergoing HDT and ASCT at our centers were reviewed under an IRB approved minimal risk protocol. Patients undergoing planned tandem autologus-allogenic transplants were excluded. MIPI elements, simplified MIPI score, and other clinical data were collected from the period immediately prior to initiation of conditioning and evaluated for their independent association with OS and PFS. Results: Between November 1995 and May 2011 190 MCL pts meeting the above criteria underwent HDT and ASCT at our centers, of these 186 (98%) had all available pretransplant MIPI data and were included in the analysis. Pretransplant MIPI scores of 0–1, 2, 3, 4, and 5–7 were seen in 27 (15%), 61 (33%), 60 (32%), 21 (11%), and 17 (9%) patients, respectively. Other baseline pretransplant characteristics included: median age 57 years (range 35–71years), elevated LDH = 48 (26%), median WBC = 4.51/μL (range 0.7 –42.43/μL), performance score 0 = 103 (55%), median prior regimens = 2 (range 1–9), blastoid variant = 16 (8%), leukemic variant = 6 (3%), chemosensitive disease = 157 (86%), and administration of rituximab (R) within 3 months prior to transplant = 139 (75%). The 8-year estimates of OS and PFS for the entire cohort were 43% (95% CI 27 – 57%) and 31% (95% CI 16 – 48%), respectively with 3 years median follow up for survivors. The pretransplant MIPI was highly associated with OS when modeled as a continuous (p=0.008) or categorical variable (p=0.002). Survival at 2 years was 88% (95% CI 78 – 93%) for MIPI 0–2, 73% (61 – 82%) for MIPI 3 or 4, and 65% (34 – 84%) for MIPI 5 or greater (Figure). Of the MIPI elements, age (hazard ratio [HR] for death 1.5 for every 10 yrs, p=0.03) and performance score (HR 1.6 for score 〉 1, p=0.08) had the greatest independent impact on OS. In addition, chemosensitive disease (HR 0.3, p 〈 0.001), number of prior regimens (p 〈 0.001), and R within 3 months prior to transplant (HR 0.6, p=0.05) were all independently associated with OS after adjusting for the pretransplant MIPI. The pretranplant MIPI score was also predictive of PFS, but less so than with OS (global and categorical p=0.02) with age providing the greatest independent association (HR for death or progression 1.3 for every 10 years, p=0.08). Again, non-MIPI factors including number of prior regimens (p 〈 0.001), blastoid variant (HR=2.1, p=.05), chemosensitive disease (HR 0.3, p 〈 0.001), and R within 3 months prior to transplant (HR=0.4, p=0.001) independently added to predictive ability of the MIPI for PFS. Conclusions: Our data suggest that the simplified MIPI score measured immediately prior to HDT and ASCT is a readily available and robust predictive tool for OS and PFS in MCL pts undergoing transplant. This score along with other clinical factors can be utilized to counsel patients and to compare results between various treatment options. The independent association of pretransplant R with improved outcomes supports its use in this setting. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.2026.2026
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 9
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    Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity
    Informa UK Limited ; 2015
    In:  Leukemia & Lymphoma Vol. 56, No. 1 ( 2015-01-02), p. 92-96
    Details
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 56, No. 1 ( 2015-01-02), p. 92-96
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    URL: Article
    DOI: 10.3109/10428194.2014.911866
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2015
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  • 10
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    Mantle Cell Lymphoma International Prognostic Index but Not Pretransplantation Induction Regimen Predicts Survival for Patients With Mantle-Cell Lymphoma Receiving High-Dose Therapy and Autologous Stem-Cell Transplantation
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 22 ( 2011-08-01), p. 3023-3029
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 22 ( 2011-08-01), p. 3023-3029
    Abstract: High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) are frequently used in an attempt to improve outcome in patients with mantle-cell lymphoma (MCL); however, the importance of intensive induction regimens before transplantation is unknown. Patients and Methods To address this question, we evaluated baseline characteristics, time to treatment, induction regimen, disease status at the time of transplantation, and MIPI score at diagnosis and their associations with survival in 118 consecutive patients with MCL who received HDT and ASCT at our centers. Results The MIPI was independently associated with survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P 〈 .001) and in the 85 patients who underwent ASCT as initial consolidation (HR, 7.2; P 〈 .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively. Low-risk MIPI scores were more common in the intensive induction group than the standard induction group in all patients (64% v 46%, respectively; P = .03) and in the initial consolidation group (66% v 45%, respectively; P = .03). After adjustment for the MIPI, an intensive induction regimen was not associated with improved survival after transplantation in all patients (HR, 0.5; P = .10), the initial consolidation group (HR, 1.1; P = .86), or patients ≤ 60 years old (HR, 0.6; P = .50). Observation of more than 3 months before initiating therapy did not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in patients receiving ASCT. Conclusion An intensive induction regimen before HDT and ASCT was not associated with improved survival after adjusting for differences in MIPI scores at diagnosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2010.33.7055
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
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