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Allogeneic hematopoietic cell transplantation is equally effective in secondary acute lymphoblastic leukemia (ALL) compared to de-novo ALL-a report from the EBMT registry
Sadowska-Klasa, A., Zaucha, J. M., Labopin, M., Bourhis, J. H., Blaise, D., Yakoub-Agha, I., Salmenniemi, U., Passweg, J., Fegueux, N., Schroeder, T., et al
Bone marrow transplantation. 2024
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Editor's Choice
Abstract
Secondary acute lymphoblastic leukemia (s-ALL) comprises up to 10% of ALL patients. However, data regarding s-ALL outcomes is limited. To answer what is the role of allogeneic hematopoietic cell transplantation (HCT) in s-ALL, a matched-pair analysis in a 1:2 ratio was conducted to compare outcomes between s-ALL and de novo ALL (dn-ALL) patients reported between 2000-2021 to the European Society for Blood and Marrow Transplantation registry. Among 9720 ALL patients, 351 (3.6%) were s-ALL, of which 80 were in first complete remission (CR1) with a known precedent primary diagnosis 58.8% solid tumor (ST), 41.2% hematological diseases (HD). The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between ST and HD patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL. To conclude, patients with s-ALL who received HCT in CR1 have comparable outcomes to patients with dn-ALL.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia, reported to the EBMT registry (n=9720)
Intervention
A detailed analysis cohort who were transplanted for secondary acute lymphoblastic leukaemia (s-ALL, n=80)
Comparison
Matched controls who were transplanted for de novo ALL (dn-ALL, n=80)
Outcome
The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between solid tumour and haematological disease patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL.
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Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation
Penack, O., Marchetti, M., Aljurf, M., Arat, M., Bonifazi, F., Duarte, R. F., Giebel, S., Greinix, H., Hazenberg, M. D., Kröger, N., et al
The Lancet. Haematology. 2024
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Editor's Choice
Abstract
Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic haematopoietic stem-cell transplantation (HSCT). In the last 3 years, there has been regulatory approval of new drugs and considerable change in clinical approaches to prophylaxis and management of GVHD. To standardise treatment approaches, the European Society for Blood and Marrow Transplantation (EBMT) has updated its clinical practice recommendations. We formed a panel of one methodologist and 22 experts in the field of GVHD management. The selection was made on the basis of their role in GVHD management in Europe and their contributions to the field, such as publications, presentations at conferences, and other research. We applied the GRADE process to ten PICO (patient, intervention, comparator, and outcome) questions: evidence was searched for by the panel and graded for each crucial outcome. In two consensus meetings, we discussed the evidence and voted on the wording and strengths of recommendations. Key updates to the recommendations include: (1) primary use of ruxolitinib in steroid-refractory acute GVHD and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD. The EBMT proposes to use these recommendations as the basis for routine management of GVHD during allogenic HSCT. The current recommendations favour European practice and do not necessarily represent global preferences.
PICO Summary
Population
Panel of 22 experts and one methdologist convened by the European Society for Blood and Marrow Transplantation (EBMT)
Intervention
Update of the EBMT consensus recommendations
Comparison
Outcome
Key updates to the recommendations include: (1) primary use of ruxolitinib in steroid-refractory acute GVHD and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD.
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Matched related versus unrelated versus haploidentical donors for allogeneic transplantation in AML patients achieving first complete remission after two induction courses: a study from the ALWP/EBMT
Nagler, A., Labopin, M., Mielke, S., Passweg, J., Blaise, D., Gedde-Dahl, T., Cornelissen, J. J., Salmenniemi, U., Yakoub-Agha, I., Reményi, P., et al
Bone marrow transplantation. 2023;58(7):791-800
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Editor's Choice
Abstract
We compared transplants (HSCT) from matched related siblings (MSD) with those from matched 10/10 and mismatched 9/10 unrelated (UD) and T-replete haploidentical (Haplo) donors in acute myeloid leukemia (AML) in first complete remission (CR1) achieved after two inductions, a known poor prognostic factor. One thousand two hundred and ninety-five patients were included: MSD (n = 428), UD 10/10 (n = 554), UD 9/10 (n = 135), and Haplo (n = 178). Acute GVHD II-IV was higher in all groups compared to MSD. Extensive chronic (c) GVHD was significantly higher in UD 9/10 (HR = 2.52; 95% CI 1.55-4.11, p = 0.0002) and UD 10/10 (HR = 1.48; 95% CI 1.03-2.13, p = 0.036) and cGVHD all grades were higher in UD 9/10 vs MSD (HR = 1.77; 95% CI 1.26-2.49, p = 0.0009). Non-relapse mortality was higher in all groups compared to MSD. Relapse incidence, leukemia-free, and overall survival did not differ significantly between donor types. Finally, GVHD-free relapse-free survival was lower in HSCT from UD 9/10 (HR = 1.56, 95% CI 1.20-2.03, p = 0.0009) but not in those from UD 10/10 (HR = 1.13, p = 0.22) and Haplo donors (HR = 1.12, p = 0.43) compared to MSD. In conclusion, in AML patients undergoing HSCT in CR1 achieved after two induction courses 10/10 UD and Haplo but not 9/10 UD donors are comparable alternatives to MSD.
PICO Summary
Population
Adults with acute myeloid leukemia (AML) in first complete remission (CR1) achieved after two inductions (n=1295)
Intervention
Allo-HSCT from matched related sibling donor (MSD, n=428)
Comparison
Matched 10/10 unrelated donor (UD 10/10 n=554), Mismatched 9/10 unrelated (UD 9/10, n=135) or T-replete haploidentical (Haplo, n=178)
Outcome
Acute GVHD II-IV was higher in all groups compared to MSD. Extensive chronic (c) GVHD was significantly higher in UD 9/10 (HR = 2.52; 95% CI 1.55-4.11) and UD 10/10 (HR = 1.48; 95% CI 1.03-2.13) and cGVHD all grades were higher in UD 9/10 vs MSD (HR = 1.77; 95% CI 1.26-2.49). Non-relapse mortality was higher in all groups compared to MSD. Relapse incidence, leukemia-free, and overall survival did not differ significantly between donor types. Finally, GVHD-free relapse-free survival was lower in HSCT from UD 9/10 (HR = 1.56, 95% CI 1.20-2.03) but not in those from UD 10/10 (HR = 1.13) and Haplo donors (HR = 1.12) compared to MSD
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Longitudinal outcome over two decades of unrelated allogeneic stem cell transplantation for relapsed/refractory acute myeloid leukemia: an ALWP/EBMT analysis
Nagler, A., Ngoya, M., Galimard, J. E., Labopin, M., Bornhäuser, M., Stelljes, M., Finke, J., Ganser, A., Einsele, H., Kröger, N., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022
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Editor's Choice
Abstract
INTRODUCTION We evaluated outcome of unrelated transplantation for primary refractory/relapsed (ref/rel) acute myeloid leukemia (AML) comparing two cohorts according to the year of transplant, 2000-2009 and 2010-2019. METHODS Multivariable analyses were performed using the Cox proportional-hazards regression model. RESULTS 3430 patients were included, 876 underwent a transplant between 2000-2009 and 2554 in 2010-2019. Median follow up was 8.7 (95% CI: 7.8-9.4) and 3.4 (95% CI: 3.1-3.6) years (p<0.001). Median age was 52 (18-77) and 56 (18-79) years (p<0.0001). 45.5% and 55.5% had refractory AML while 54.5% and 44.5 % had relapsed AML. Conditioning was myeloablative in 60% and 52%, respectively. Neutrophil recovery, day 100 incidence of acute and 2-year incidence of chronic graft-versus-host disease (GVHD) were similar between the two periods. Two-year relapse incidence was higher for patients transplanted in the 2000-2009 period vs. those transplanted in 2010-2019; 50.2% vs. 45.1%; (hazard ratio (HR)=0.85 (95% CI: 0.74-0.97), p=0. 002). Leukemia-free survival, overall survival and GVHD-free, relapse-free survival were lower for the 2000-2009 period, 26% vs. 32.1% (HR=0.87 (95% CI: 0.78-0.97), p=0.01), 32.1% vs. 38.1% (HR=0.86 (95% CI: 0.77-0.96), p=0.01) and 21.5% vs. 25.3% (HR=0.89 (95% CI: 0.81-0.99), p=0.03, respectively. Two-year non-relapse mortality was not significantly different, 23.8% vs. 23.7% (HR=0.91 (95% CI: 0.76-1.11), p=0.34. CONCLUSION Outcome of unrelated transplantation for patients with ref/rel AML has improved in the last two decades, rescuing about one third of the patients.
PICO Summary
Population
Adults transplanted for refractory/relapsed acute myeloid leukaemia (AML) and reported to the EBMT registry (n=3430)
Intervention
Transplantation between the years 2000-2009 (n=876)
Comparison
Transplantation between the years 2010-2019 (n=2554
Outcome
Median follow up was 8.7 (95% CI: 7.8-9.4) and 3.4 (95% CI: 3.1-3.6) years (2000-2009 and 2010-2019 respectively). Median age was 52 (18-77) and 56 (18-79) years. 45.5% and 55.5% had refractory AML while 54.5% and 44.5 % had relapsed AML. Conditioning was myeloablative in 60% and 52%, respectively. Neutrophil recovery, day 100 incidence of acute and 2-year incidence of chronic graft-versus-host disease (GVHD) were similar between the two periods. Two-year relapse incidence was higher for patients transplanted in the 2000-2009 period vs. those transplanted in 2010-2019; 50.2% vs. 45.1%; (hazard ratio (HR)=0.85 (95% CI: 0.74-0.97)). Leukemia-free survival, overall survival and GVHD-free, relapse-free survival were lower for the 2000-2009 period, 26% vs. 32.1% (HR=0.87 (95% CI: 0.78-0.97), 32.1% vs. 38.1% (HR=0.86 (95% CI: 0.77-0.96)) and 21.5% vs. 25.3% (HR=0.89 (95% CI: 0.81-0.99), respectively. Two-year non-relapse mortality was not significantly different, 23.8% vs. 23.7% (HR=0.91 (95% CI: 0.76-1.11).
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Autologous hematopoietic cell transplantation for relapsed multiple myeloma performed with cells procured after previous transplantation-study on behalf of CMWP of the EBMT
Drozd-Sokołowska, J., Gras, L., Zinger, N., Snowden, J. A., Arat, M., Basak, G., Pouli, A., Crawley, C., Wilson, K. M. O., Tilly, H., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse.
PICO Summary
Population
Patients with multiple myeloma who relapsed after first autologous stem cell transplant (n=305)
Intervention
Stem cell remobilisation and autologous stem cell transplant (auto-HCT)
Comparison
None
Outcome
The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS.
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Mocravimod, a selective S1PR modulator in allogeneic hematopoietic stem cell transplantation for malignancy
Dertschnig, S., Gergely, P., Finke, J., Schanz, U., Holler, E., Holtick, U., Socié, G., Medinger, M., Passweg, J., Teshima, T., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for patients with acute myelogenous leukemia (AML). Outcomes are limited by leukemia relapse, graft-versus-host disease (GvHD) and abnormal immune reconstitution. Mocravimod (KRP203) is an oral sphingosine-1-phosphate receptor (S1PR) modulator that blocks the signal required by T cells to egress from lymph nodes and other lymphoid organs. Mocravimod retains T cell effector function, a main differentiator to immunosuppressants. In preclinical models, mocravimod improves survival by maintaining graft-versus-leukemia (GvL) activity while reducing GvHD. In patients undergoing allo-HSCT for hematological malignancies, mocravimod is postulated to prevent GvHD by redistributing allogeneic donor T cells to lymphoid tissues while allowing sufficient GvL in the lymphoid where malignant cell usually reside. OBJECTIVES Primary objective of the study was to assess the safety and tolerability of mocravimod in subjects undergoing allo-HSCT for hematological malignancies. Secondary objectives were to determine the pharmacokinetic profile of mocravimod and its active metabolite mocravimod-phosphate in this patient group as well as to assess GvHD-free, relapse free survival at 6 months after last treatment. STUDY DESIGN In this two-part, single- and two-arm randomized, open-label trial we evaluated the safety, tolerability, and pharmacokinetics of mocravimod in allo-HSCT recipients (clinicaltrials.gov; NCT01830010). Subjects received either 1 mg or 3 mg mocravimod/day on top of standard of care GvHD prophylaxis with either cyclosporine A/methotrexate or tacrolimus/methotrexate. RESULTS We found that the S1PR modulator mocravimod can safely be added to standard treatment regimens in patients with hematological malignancies requiring allo-HSCT. Mocravimod resulted in a significant reduction of circulating lymphocyte numbers and had no negative impact on engraftment and transplant outcomes. CONCLUSIONS Mocravimod is safe and the here presented results support a larger study to investigate efficacy in a homogeneous AML patient population undergoing allo-HSCT.
PICO Summary
Population
Adults undergoing allo-HSCT for haematological malignancies (n=23)
Intervention
3 mg mocravimod/day on top of standard of care GvHD prophylaxis: either cyclosporine A/methotrexate or tacrolimus/methotrexate (Mo3CsA, n=10) or mocravimod plus tacrolimus/MTX (Mo3Tac, n=7).
Comparison
1 mg/day mocravimod on top of standard of care GvHD prophylaxis, cyclosporine A/methotrexate (Mo1CsA, n=6)
Outcome
Mocravimod resulted in a significant reduction of circulating lymphocyte numbers and had no negative impact on engraftment and transplant outcomes.
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Allogeneic hematopoietic cell transplantation in patients with CML chronic phase in the era of third generation tyrosine kinase inhibitors: a retrospective study by the Chronic Malignancies Working Party of the EBMT
Chalandon, Y., Sbianchi, G., Gras, L., Koster, L., Apperley, J., Byrne, J., Salmenniemi, U., Sengeloev, H., Aljurf, M., Helbig, G., et al
American journal of hematology. 2022
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Editor's Choice
Abstract
Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT) for chronic phase (CP) CML has dramatically decreased. Imatinib was the 1(st) TKI introduced to the clinical arena, predominantly utilised in the 1(st) line setting. In cases of insufficient response, resistance or intolerance, CML patients can subsequently be treated with either a 2(nd) or 3(rd) generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2 or 3 TKI prior to allo-HCT for CP CML in 904 patients. A total of 323-, 371- and 210 patients had 1, 2 or 3 TKI prior to transplant respectively; imatinib (n=778), dasatinib (n=508), nilotinib (n=353), bosutinib (n=12) and ponatinib (n=44). The majority had imatinib as first TKI (n=747, 96%). Transplants were performed in CP1, n=549, CP2, n=306, and CP3, n=49. With a median follow-up of 52 months, 5-year OS for the entire population was 64.4% (95% CI 60.9-67.9 %), PFS 50% (95% CI 46.3-53.7%), RI 28.7% (95% CI 25.4-32.0%) and NRM 21.3% (95% CI 18.3-24.2%). No difference in OS, PFS, RI or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI (p=ns). Significant factors influencing OS and PFS were >CP1 vs CP1 and Karnofsky performance (KPS) score > 80 vs ≤80, highlighting CP1 patients undergoing allo-HCT have improved survival compared to >CP1 and the importance of careful allo-HCT candidate selection. This article is protected by copyright. All rights reserved.
PICO Summary
Population
Adults, identified from the EBMT registry who had chronic myeloid leukaemia and received tyrosine kinase inhibitor (TKI) therapy prior to first allogeneic transplant (n=904)
Intervention
1 TKI prior to transplant (n=323)
Comparison
2 TKI prior to transplant (n=371); 3 TKI prior to transplant (n=210)
Outcome
With a median follow-up of 52 months, 5-year overall survival (OS) for the entire population was 64.4% (95% CI 60.9-67.9 %), Progression free survival (PFS) 50% (95% CI 46.3-53.7%), relapse incidence (RI) 28.7% (95% CI 25.4-32.0%) and non-relapse mortality (NRM) 21.3% (95% CI 18.3-24.2%). No difference in OS, PFS, RI or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI. Significant factors influencing OS and PFS were chronic phase (CP) >1 vs CP1 and Karnofsky performance score > 80 vs </=80.
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Measurable residual disease (MRD) status before allogeneic hematopoietic cell transplantation impact on secondary acute myeloid leukemia outcome. A Study from the Acute Leukemia Working Party (ALWP) of the European society for Blood and Marrow Transplantation (EBMT)
Maffini, E., Labopin, M., Beelen, D. W., Kroeger, N., Arat, M., Wilson, K. M. O., Bay, J. O., Ganser, A., Martin, H., Passweg, J., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Measurable residual disease (MRD) assessment before allogeneic hematopoietic cell transplantation (HCT) may help physicians to identify a subgroup of patients at high risk of relapse for de novo acute myeloid leukemia (AML) but its relevance among patients affected by secondary AML (sAML) is still unknown. We assessed the impact of MRD among 318 adult patients with sAML who received an allogeneic HCT in first complete remission. At the time of HCT, a total of 208 (65%) patients achieved MRD negativity, while 110 (35%) had positive MRD. 2-year overall survival (OS) was 58.8 % (95% CI 52.2-64.9) with leukemia-free survival (LFS) of 50.0 % (95% CI 43.7-56.1), relapse incidence of 34.2% (95% CI 28.4-40.1) and non-relapse mortality (NRM) of 23.3 % (95% CI 19-27.7) for the entire cohort. In multivariate analysis, HCT recipients with KPS ≥ 90 experienced less disease recurrence (HR 0.61, 95% CI 0.4-0.94) with better LFS (HR 0.63, 95% CI 0.44-0.89) and OS (HR 0.58, 95% CI 0.39-0.86). There were no differences in major clinical endpoints between patients with MRD-positive and MRD-negative status at the time of HCT. Pre-transplantation assessment of MRD was not informative on post-HCT outcomes in this retrospective registry-based analysis among patients affected by sAML.
PICO Summary
Population
Adults with secondary acute myeloid leukaemia reported to the EBMT registry (n=318)
Intervention
Measurable residual disease (MRD) negativity prior to allogeneic transplant (n=208)
Comparison
Positive MRD at transplantation (n=110)
Outcome
2-year overall survival (OS) was 58.8 % (95% CI 52.2-64.9) with leukemia-free survival (LFS) of 50.0 % (95% CI 43.7-56.1), relapse incidence of 34.2% (95% CI 28.4-40.1) and non-relapse mortality (NRM) of 23.3 % (95% CI 19-27.7) for the entire cohort. In multivariate analysis, HCT recipients with KPS ≥ 90 experienced less disease recurrence (HR 0.61, 95% CI 0.4-0.94) with better LFS (HR 0.63, 95% CI 0.44-0.89) and OS (HR 0.58, 95% CI 0.39-0.86). There were no differences in major clinical endpoints between patients with MRD-positive and MRD-negative status at the time of HCT.
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Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT
Kröger, N., Sbianchi, G., Sirait, T., Wolschke, C., Beelen, D., Passweg, J., Robin, M., Vrhovac, R., Helbig, G., Sockel, K., et al
Leukemia. 2021
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Editor's Choice
Abstract
JAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n?=?274) or with (n?=?277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p?=?0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p?=?0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p?=?0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age?>?58 years (p?=?0.03) and HLA mismatch donor (p?=?0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.
PICO Summary
Population
Patients with myelofibrosis who received allogeneic stem cell transplantation (n=551)
Intervention
Pretreatment ruxolitinib (n=277)
Comparison
No ruxolitinib (n=274)
Outcome
The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%) and better 2-year event-free survival (68.9% vs. 53.7%) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age>58 years and HLA mismatch donor. RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.
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10.
Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT
Gagelmann, N., Eikema, D. J., de Wreede, L. C., Rambaldi, A., Iacobelli, S., Koster, L., Caillot, D., Blaise, D., Remémyi, P., Bulabois, C. E., et al
Bone marrow transplantation. 2020
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Editor's Choice
Abstract
We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n?=?446), auto-auto (n?=?105), or auto-allo (n?=?72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p?=?0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p?=?0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p?=?0.007) and auto-allo (HR, 0.45; p?=?0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p?=?0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p?=?0.097). No significant difference in OS was identified between the groups in patients with del(17p).
PICO Summary
Population
Patients with newly diagnosed myeloma with del(17p) and/or t(4;14) (n=623)
Intervention
Autologous transplant (auto, n=446), tandem autologous (auto-auto, n=105)
Comparison
tandem autologous/reduced intensity allogeneic transplant (auto-allo, n=72)
Outcome
Five-year overall survival (OS) was 51% for single auto, 60% for auto-auto, and 67% for auto-allo Five-year progression-free survival (PFS) was 17%, 33%, and 34%. Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44) and auto-allo (HR, 0.45) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49;). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65).