| 1. |
- Chhabra, Saurabh, et al.
(författare)
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Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:21, s. 2922-2936
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.
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| 2. |
- DeFilipp, Zachariah, et al.
(författare)
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Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia : A Center for International Blood and Marrow Transplant Research Study
- 2020
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined.
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| 3. |
- Hill, Brian T., et al.
(författare)
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Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia
- 2018
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:3, s. 581-586
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL.
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| 4. |
- Hu, Bei, et al.
(författare)
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Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients
- 2020
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:12, s. 2811-2820
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Tidskriftsartikel (refereegranskat)abstract
- While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2-4.9;p = .02). In BP CML, there was a trend toward higher survival with alloHCT; HR = 0.7 (0.5-1.1;p = .099). AlloHCT in CP2 + [HR = 2.0 (0.8-4.9),p = .13] and AP [HR = 1.1 (0.6-2.1);p = .80] is less clear and should be determined on a case-by-case basis.
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| 5. |
- Kim, Haesook T., et al.
(författare)
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Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients : Center for International Blood and Marrow Transplant Research Report
- 2019
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:16, s. 5143-5155
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >= 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
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| 6. |
- Kumar, Rajat, et al.
(författare)
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Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions.
- 2016
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Ingår i: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. - : Elsevier BV. - 1523-6536. ; 22:5, s. 932-940
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared with mobilized peripheral blood stem cells (PBSCs). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita and region/countries into 4 groups. Groups analyzed were high-income countries (HIC), which were further divided into United States-Canada (n=486) and other HIC (n=1264); upper middle income (UMIC) (n=482); and combined lower-middle, low-income countries (LM-LIC) (n=142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared with PBSCs in all countries or BM in UMIC or LM-LIC (P<.001). There was no significant difference in OS between BM and PBSCs in UMIC (P=.32) or LM-LIC (P=.23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSCs compared with BM (97% versus 77%, P<.001). Chronic graft-versus-host disease was significantly higher with PBSCs in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSCs may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications.
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| 7. |
- Liu, Hien Duong, et al.
(författare)
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Allogeneic Hematopoietic Cell Transplantation for Adult Chronic Myelomonocytic Leukemia
- 2017
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Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 23:5, s. 767-775
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for patients with chronic myelomonocytic leukemia (CMML); however, few data exist regarding prognostic factors and transplantation outcomes. We performed this retrospective study to identify prognostic factors for post-transplantation outcomes. The CMML-specific prognostic scoring system (CPSS) has been validated in subjects receiving nontransplantation therapy and was included in our study. From 2001 to 2012, 209 adult subjects who received HCT for CMML were reported to the Center for International Blood and Marrow Transplant Research. The median age at transplantation was 57 years (range, 23 to 74). Median follow-up was 51 months (range, 3 to 122). On multivariate analyses, CPSS scores, Karnofsky performance status (KPS), and graft source were significant predictors of survival (P = .004, P = .01, P = .01, respectively). Higher CPSS scores were not associated with disease-free survival, relapse, or transplantation-related mortality. In a restricted analysis of subjects with relapse after HCT, those with intermediate-2/high risk had a nearly 2-fold increased risk of death after relapse compared to those with low/intermediate-1 CPSS scores. Respective 1-year, 3-year, and 5-year survival rates for low/intermediate-1 risk subjects were 61% (95% confidence interval [CI], 52% to 72%), 48% (95% CI, 37% to 59%), and 44% (95% CI, 33% to 55%), and for intermediate-2/high risk subjects were 38% (95% CI, 28% to 49%), 32% (95% CI, 21% to 42%), and 19% (95% CI, 8% to 29%). We conclude that higher CPSS score at time of transplantation, lower KPS, and a bone marrow graft are associated with inferior survival after HCT. Further investigation of CMML disease-related biology may provide insights into other risk factors predictive of post-transplantation outcomes. (C) 2017 American Society for Blood and Marrow Transplantation.
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| 8. |
- Wood, William A., et al.
(författare)
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Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival in Acute Lymphoblastic Leukemia : A CIBMTR Analysis
- 2018
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Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 24:9, s. 1928-1935
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Tidskriftsartikel (refereegranskat)abstract
- For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed using the following macroeconomic indicators as main effects: Gross national income per capita, health expenditure per capita, and Human Development Index (HDI). The outcome was overall survival at 100 days following transplantation. In each model, transplants performed within lower resourced environments were associated with inferior overall survival. In the model with the HDI as the main effect, transplants performed in the lowest HDI quartile (n = 697) were associated with increased hazard for mortality (hazard ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with transplants performed in the countries with the highest HDI quartile. This translated into an 11% survival difference at 100 days (77% for lowest HDI quartile versus 88% for all other quartiles). Country-level macroeconomic indices were associated with lower survival at 100 days after alloHCT for ALL. The reasons for this disparity require further investigation.
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