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  • American Society of Hematology  (6)
  • 1
    Online Resource
    Online Resource
    Effect of Interventions for Relapse or Progression Following Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience of 93 Patients.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1648-1648
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1648-1648
    Abstract: Background: Relapse/progression after allogeneic hematopoietic cell transplantation (HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome in a modern transplant setting was overviewed to improve decision-making. Patients and immediate therapy: Between 2000 and 2006, 294 patients with leukemia/MDS received allogeneic HCT after myeloablative (n=145) or reduced-intensity (n=149) conditioning. Among them, 93 patients (32%) either relapsed or showed disease progression; the relapse rate was 40% for AML (57/144 patients), 18% for MDS (13/72), 14% for CML (5/35), and 42% for ALL (18/43). The median overall survival (OS) after relapse or progression was 167 days (range; 5 to 1456 days). Twenty-eight patients (30%) were elected to receive no interventions with curative intent other than withdrawal of immunosuppressant, less-intensive chemotherapy or DLI, mostly due to comorbidities or refractoriness of the disease, and all but 3 patients died with disease progression at a median of 61 days. Two other patients underwent immediate HCT without intervention due to graft failure. Among the remaining 63 patients (68%) who received therapeutic interventions including re-induction chemotherapy with or without DLI, 26 (41%) achieved subsequent complete remission (CR). Salvage transplantation: Forty-five patients (15 in CR and 30 in non-CR) did not undergo a second HCT due to various reasons including progressive disease (n=28), infection (n=6), GVHD (n=3), refusal (n=3), and rather stable disease (n=5). Overall, 20 patients underwent salvage HCT using myeloablative (n=8) or reduced-intensity (n=12) conditioning: 11 in CR and 9 in non-CR. The incidence of TRM after the second HCT was not remarkable (5%). The probability of achieving CR after the second HCT was 75%, compared to 35% after other interventions (p=0.001), and the 1-year OS after relapse was significantly better in patients with the second HCT than that in others (58% vs 14%, p & lt;0.0001), but these favorable outcomes may simply reflect the patient-selection bias. The 2-year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after a second HCT. Currently, 15 of the 93 patients (16%) are alive with a median follow-up of 346 days (range; 33 to 1456 days), and 10 of these patients are still in CR. Notably, 5 patients are alive in CR without a second HCT: 3 suffered from central nervous system relapse without systemic relapse and received localized therapy alone (follow-up; 494 to 1456 days), and the remaining 2 have had a rather short follow-up after DLI. Multivariate analysis showed that re-induction chemotherapy, CR after intervention, a second HCT, and a longer time to post-transplantation relapse (≥100 days) were associated with improved OS after relapse. Conclusion: For patients with chemosensitive systemic relapse, a second allogeneic HCT may improve survival and could be considered as an effective therapeutic option. Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1648.1648
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
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  • 2
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    Multicenter Phase II Clinical Trial of Nilotinib for Patients with Imatinib-Resistant or Intolerant CML From the East Japan CML Study Group (EJCML) Trial: Evaluation of Molecular Responses by the BCR-ABL1 Mutational Status and Plasma Trough Concentration of Nilotinib
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 1360-1360
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1360-1360
    Abstract: Abstract 1360 Introduction: The tyrosine kinase inhibitor (TKI) imatinib is used as the first-line therapy for newly diagnosed chronic myeloid leukemia (CML). However, some patients fail to respond or become intolerant to imatinib. Nilotinib is a second-generation TKI with higher selectivity and more potent inhibitory effects on BCR-ABL than imatinib. Several studies have shown hematologic and cytogenetic responses to nilotinib in patients with imatinib-resistant or intolerant CML. Purpose: To investigate the safety and efficacy of nilotinib for patients with imatinib-resistant or intolerant, chronic (CP)- or accelerated (AP)-phase CML from the East Japan CML Study Group (EJCML) trial by evaluating molecular responses in terms of the BCR-ABL1 mutational status and plasma trough concentration of nilotinib. Methods: In this multicenter phase II clinical trial, nilotinib (400 mg bid) was administered orally for one year and the molecular responses were monitored by means of the international scale of quantitative PCR (IS-PCR). BCR-ABL1 mutations were analyzed by direct sequencing at the baseline and 12 months or at the time of the event for discontinuation of the treatment (i.e., progressive disease, insufficient effects, or severe adverse events). The plasma trough concentration of nilotinib was measured by high-performance liquid chromatography 3 months after nilotinib administration. Results: From March 2009 through February 2011, 51 patients were registered in this study, and data of 49 patients whose molecular responses were evaluated by the IS-PCR were analyzed (imatinib-resistant CML = 33, imatinib-intolerant CML = 16; CP CML = 46, AP CML = 3). The median follow-up period was 12.0 months (range = 0.1–13.3 months). At 6 and 12 months, the major molecular response (MMR; ≤0.1% IS) rates were 52.5% and 67.6%, respectively, and the complete cytogenetic response (CCyR)-equivalent (≤1.0% IS) rates were 75.0% and 85.3%, respectively. Five types of BCR-ABL1 mutations (M244V, F317L, N358D, F359V, and E459K) were detected in 6 patients (12.2%) at the baseline, but the M244V, N358D, and E459K mutations disappeared after the nilotinib treatment. Acquired BCR-ABL1 mutations (Y253H, I418V, and exon 8/9 35bp insertion) were detected in 3 patients (8.6%) at 12 months or at the time of the event; these patients did not achieve a CCyR or an MMR. No patients showed an acquired mutation of T315I. Most patients except 11 subjects (22.4%) still received the treatment. The reasons for discontinuation were progressive disease in one patient with an F317L mutation, insufficient effects in one patient without any mutation, and adverse events in 9 patients (thrombocytopenia in 5 patients, hyperbilirubinemia in 2 patients, headache in one patient, and heart disease in one patient). Among 30 patients without BCR-ABL1 mutations, the plasma trough concentration of nilotinib was significantly higher in 21 patients with an MMR than in those without an MMR by 12 months (median = 1255.1 ng/mL vs. 372.8 ng/mL, P = 0.0012 by Mann–Whitney U-test; see the figure). The concentration of 761 ng/mL was significantly associated with an MMR by 12 months in a receiver-operating characteristic (ROC) curve analysis of the best sensitivity (76.2%) and specificity (77.8%). Conclusion: The patients with imatinib-resistant or intolerant, CP or AP CML, even those having BCR-ABL1 mutations M244V, N358D, and E459K, achieved an MMR by 12 months of nilotinib treatment. The plasma trough concentration of the drug was related to the MMR by 12 months, and the plasma threshold of nilotinib should be set above 761 ng/mL. These findings suggest that nilotinib shows good efficacy and tolerability in Japanese patients with imatinib-resistant or intolerant, CP or AP CML. (ClicalTrials.gov, UMIN ID 000002201) Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.1360.1360
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
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    Impact of T-Cell Chimerism on Clinical Outcome in 117 Patients Who Underwent Allogeneic Stem Cell Transplantation with a Busulfan-Containing Reduced-Intensity Conditioning Regimen.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 2009-2009
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2009-2009
    Abstract: Background: Within the concept of reduced-intensity stem cell transplantation (RIST), there is a wide range of differences in regimens utilized, in terms of toxicities and antileukemia effects, and only a little information is available on the clinical impact of chimerism status in patients conditioned with a busulfan-containing regimen. To examine this point, we reviewed the pattern of lineage-specific chimerism to correlate with subsequent clinical outcomes. Patients and Methods: We retrospectively reviewed the data of 117 patients (median age, 52 years: range, 29–68) who had various hematological malignancies and underwent busulfan-containing RIST with related blood stem cells (n=81), related marrow (n=4) or unrelated marrow (n=32), between January 2000 and December 2006. The conditioning regimen consisted of busulfan (8 mg/kg) and fludarabine (180 mg/m2, n=64) or cladribine (0.66 mg/kg, n=53), with or without 2–4 Gy TBI (n=26) or anti-thymocyte globulin (5–10 mg/kg: n=31). Prophylaxis for GVHD consisted of cyclosporin or tacrolimus, with or without methotrexate. Chimerism was evaluated with peripheral blood samples taken on days 30, 60 and 90 after transplantation by PCR-based amplification of polymorphic short tandem repeat regions. Results: The median follow-up of surviving patients was 857 days (50–2535). Percent donor-chimerism was significantly higher in granulocytes than T-cell fraction throughout the entire course, and the mean values were, respectively, 96% vs 83%, 98% vs 89% and 98% vs 91% at days 30, 60 and 90 after RIST. At day 30, the numbers of patients with T-cell chimerism & gt;90%, 60–90% and & lt;60% were 67 (58%), 32 (27%) and 18 (15%), respectively. The mean percentage of donor T-cell chimerism on day 30 was 18% (0–63%) in 5 patients who experienced graft failure (GF), which was significantly lower than that (86%; 15–100%) in the rest of the patients (p & lt;0.01). No correlation was found between the kinetics of T-cell chimerism and the occurrence of acute or chronic GVHD. A multivariate analysis showed that low donor T-cell chimerism of & lt;60% at day 30 was significantly associated with an increased risk of treatment failure (TF) at day 100, which included GF, progressive disease, relapse and non-relapse mortality (HR: 3.3 [95% CI, 1.4–7.8] p & lt;0.01), but not with 1-year TF. The stem cell source and the addition of TBI or ATG were not associated with the degree of T-cell chimerism, overall survival (OS) or TF. In a Cox proportional hazard model, low donor T-cell chimerism of & lt;60% at day 30 was associated with poor OS (HR: 2.2 [95% CI, 1.1–4.4] p=0.02) (Figure) and TF (HR: 2.0 [95% CI, 1.1–3.8] p=0.02). Conclusion: We found that 42% of the patients retained mixed donor T-cell chimerism (≤90% donor), whereas 92% achieved complete chimerism in granulocyte fraction. Low donor T-cell chimerism of & lt;60% at day 30 may predict a poor outcome, and a prospective study to examine the value of early intervention based on chimerism data is warranted. Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.2009.2009
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 4
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    TT Virus in Bone Marrow Transplant Recipients
    American Society of Hematology ; 1999
    In:  Blood Vol. 93, No. 8 ( 1999-04-15), p. 2485-2490
    Details
    In: Blood, American Society of Hematology, Vol. 93, No. 8 ( 1999-04-15), p. 2485-2490
    Abstract: TT virus (TTV) is a newly discovered transfusion-transmissible DNA virus, which may cause posttransfusion hepatitis. The virus was detected in 12% of Japanese blood donors. The aim of the study is to investigate the prevalence and clinical influence of TTV in bone marrow transplant (BMT) recipients. Sera from 25 BMT recipients obtained 6 to 12 weeks after the transplant were examined for TTV-DNA by the seminested polymerase chain reaction. Serial samples were additionally analyzed in patients with TTV-DNA. Fifteen of 25 recipients (60%) were positive for TTV-DNA after transplant, whereas it was detected in only two of 20 BMT donors (10%). In patients positive for TTV-DNA before BMT, the amount of TTV-DNA decreased to an undetectable level during the myelosuppressed period after BMT. We also found that there was a novel group of TTV, G3, classified by the nucleotide sequences. The median peak alanine aminotransferase (ALT) levels were 135.0 IU/L and 116.5 IU/L (normal range, 4 to 36 IU/L) in TTV-positive and TTV-negative recipients, respectively. In one of the seven TTV-positive patients who developed hepatic injury (ALT & gt; 150 IU/L), a serial change in the serum TTV titer showed a good correlation with the ALT level. We concluded that (1) the prevalence of TTV is high in BMT recipients, (2) TTV might be replicated mainly in hematopoietic cells, (3) transfusion-transmitted TTV may cause persistent infection, (4) a novel genetic group of TTV, G3, was discovered, and (5) TTV does not seem to frequently cause hepatic injury, although one patient was strongly suggested to have TTV-induced hepatitis.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V93.8.2485
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1999
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
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    TT Virus in Bone Marrow Transplant Recipients
    American Society of Hematology ; 1999
    In:  Blood Vol. 93, No. 8 ( 1999-04-15), p. 2485-2490
    Details
    In: Blood, American Society of Hematology, Vol. 93, No. 8 ( 1999-04-15), p. 2485-2490
    Abstract: TT virus (TTV) is a newly discovered transfusion-transmissible DNA virus, which may cause posttransfusion hepatitis. The virus was detected in 12% of Japanese blood donors. The aim of the study is to investigate the prevalence and clinical influence of TTV in bone marrow transplant (BMT) recipients. Sera from 25 BMT recipients obtained 6 to 12 weeks after the transplant were examined for TTV-DNA by the seminested polymerase chain reaction. Serial samples were additionally analyzed in patients with TTV-DNA. Fifteen of 25 recipients (60%) were positive for TTV-DNA after transplant, whereas it was detected in only two of 20 BMT donors (10%). In patients positive for TTV-DNA before BMT, the amount of TTV-DNA decreased to an undetectable level during the myelosuppressed period after BMT. We also found that there was a novel group of TTV, G3, classified by the nucleotide sequences. The median peak alanine aminotransferase (ALT) levels were 135.0 IU/L and 116.5 IU/L (normal range, 4 to 36 IU/L) in TTV-positive and TTV-negative recipients, respectively. In one of the seven TTV-positive patients who developed hepatic injury (ALT 〉 150 IU/L), a serial change in the serum TTV titer showed a good correlation with the ALT level. We concluded that (1) the prevalence of TTV is high in BMT recipients, (2) TTV might be replicated mainly in hematopoietic cells, (3) transfusion-transmitted TTV may cause persistent infection, (4) a novel genetic group of TTV, G3, was discovered, and (5) TTV does not seem to frequently cause hepatic injury, although one patient was strongly suggested to have TTV-induced hepatitis.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V93.8.2485.408k06_2485_2490
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1999
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
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    Overall Survival in Acquired Pure Red Cell Aplasia in Adults Following Immunosuppressive Therapy: Preliminary Results from the Nationwide Cohort Study (PRCA2016)
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2593-2593
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2593-2593
    Abstract: Background. Idiopathic PRCA and secondary PRCA not responding to the treatment of the underlying diseases are generally treated by immunosuppressive therapy. Because of the rarity of this disease, there are few reports regarding the long-term outcome following immunosuppression. We previously conducted the nationwide study for chronic PRCA in Japan that had been diagnosed between 1990 and 2006 across 109 institutions, and collected the data on a total of 185 patients (PRCA2004/2006 study). This study revealed that poor response to induction therapy and relapse of anemia were associated with death. There was no significant difference in survival between idiopathic and secondary PRCA in the PRCA2004/2006 study cohort. Objective. In order to identify the adverse risk factors for survival in acquired PRCA following immunosuppression in a prospective way, we have conducted another nationwide cohort study for acquired PRCA in adults (PRCA2016 study). The primary endpoint is the overall survival (OS) and the secondary endpoints include efficacy of immunosuppression, causes of treatment failure and survival times with iron-chelation therapy. Methods. This is designed as a prospective longitudinal observational study. Between 2006 and 2014, 554 PRCA patients were registered in the hematological disorder registry managed by the Japanese Society of Hematology. We sent the first questionnaires to the physicians asking for collaboration with this study and the responses showed the potential size of cohort was 181 patients (Fig. 1). We then sent the second questionnaires to collect data regarding underlying disease, laboratory findings including CBC and leukocyte differentials, results of bone marrow examination, immunological and cytogenetics, efficacy of immunosuppression, iron-chelation therapy in refractory cases and outcome. The review boards of participating institutions and the ethical committee of the JSH approved this study and informed consent was obtained from the patients. Results. As of June 16, 2018, 103 patients were registered in this study. Fifty-two patients were classified as having idiopathic PRCA and 51 patients as having secondary PRCA, including 16 thymoma- and 5 large granular lymphocyte (LGL) leukemia-associated PRCA. Seventy-one patients were treated with immunosuppressive agents. The response rates of cyclosporine, predonisolone, cyclophosphamide, azathioprine and combination with more than one immunosuppressants were 84% (43/51), 89% (8/9), 100% (2/2), 0% (0/1), 60% (9/15), respectively (Fig. 2). The Kaplan-Meyer estimates of the survival revealed that the estimated median survival time in idiopathic PRCA was 6,430 days and that in secondary PRCA has not yet been reached (Fig. 3). Survival time was not significantly different between the two subtypes of PRCA. Twenty-two deaths were reported and the major causes of death were infection and heart failure. Discussion/Conclusion. The most common subtypes of chronic PRCA in Japan were idiopathic, thymoma-associated and LGL leukemia-associated PRCA and this result was consistent with our observation in the PRCA2004/2006 study. Cyclosporine and prednisolone were frequently chosen for the induction therapy resulting in favorable responses. Preferential use of these two agents might reflect the physician's concern about the toxicity of the cytotoxic drugs. The median survival time of idiopathic PRCA was quite similar to the results in the previous cohort study. No significant difference in survival between idiopathic and secondary PRCA has been confirmed by the present study. These two cohort studies clearly indicate that novel diagnostic and predictive biomarkers should be developed to segregate the good and poor responders to immunosuppressive therapy in PRCA. Disclosures Nakao: Novartis: Honoraria; Kyowa Hakko Kirin Co., Ltd.: Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria. Yonemura:Alexion Pharma: Honoraria, Research Funding. Matsuda:GlaxoSmithKline K.K.: Honoraria; Novartis Pharma K. K.: Honoraria; Chugai Pharmaceutical Co, Ltd.: Honoraria; Kyowa Hakko Kirin Co, Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Nippon Shinyaku Co., Ltd.: Honoraria; Celgene Corporation: Honoraria; Alexion Pharmaceuticals, Inc.: Honoraria; Sanofi K.K.: Honoraria; Beckman Coulter K.K.: Honoraria. Kurokawa:Otsuka Pharmaceutical: Research Funding; Astellas Pharma: Research Funding; MSD: Honoraria, Research Funding; Pfizer: Research Funding; Eizai: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Research Funding; Teijin Pharma: Research Funding; Nippon Sinyaku: Honoraria, Research Funding; Takeda Pharmaceutical: Research Funding; Chugai Pharmaceutical: Research Funding; Kyowa Hakko Kirin: Honoraria, Research Funding. Arai:Novartis: Research Funding. Mitani:Kyowa Hakko Kirin Co., Ltd.: Consultancy, Research Funding, Speakers Bureau; Bristol-Myesr Squibb: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Chugai: Research Funding; Astellas: Research Funding; Sumitomo Dainippon: Research Funding; Novartis: Research Funding; Toyama Chemical: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-99-114245
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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