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The outcome of patients with Hodgkin lymphoma and early relapse after autologous stem cell transplant has improved in recent years
Bazarbachi, A., Boumendil, A., Finel, H., Khvedelidze, I., Romejko-Jarosinska, J., Tanase, A., Akhtar, S., Ben Othman, T., Ma'koseh, M., Afanasyev, B., et al
Leukemia. 2022
Abstract
Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting.
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Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study
Greinix, H. T., Eikema, D. J., Koster, L., Penack, O., Yakoub-Agha, I., Montoto, S., Chabannon, C., Styczynski, J., Nagler, A., Robin, M., et al
Haematologica. 2021
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Editor's Choice
Abstract
Acute graft-versus-host disease (aGvHD) remains a major threat to successful outcome after allogeneic hematopoietic cell transplantation. Advances in prophylaxis and supportive care have taken place over the years. The aim of this study is to test whether incidence and mortality of aGvHD have been reduced over time. 102 557 patients with a median age of 47.6 years with malignancies after first allogeneic sibling or unrelated donor (URD) transplant were studied in the following periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015. Findings: 100-day-incidences of aGvHD grades II-IV decreased from 40%, to 38%, 32%, 29% and 28% over calendar time (p.
PICO Summary
Population
Patients undergoing first allogeneic sibling or unrelated donor transplant (URD) between 1990 and 2015 (n=102 557)
Intervention
Registry data study assessing incidence of acute GvHD (aGvHD)
Comparison
Patients were compared in the following time periods: 1990-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015
Outcome
In multivariate analysis URD, not in CR at transplant or untreated, and female donor for male recipient were associated with increased risk whereas use of ATG/alemtuzumab decreased aGvHD incidence. Median follow-up was 214, 169, 127, 81 and 30 months for periods analyzed. 3-year-survival after aGvHD grades II-IV increased significantly from 38% to 40%, 43%, 44%, and 45%. In multivariate analysis URD, not in CR at transplant, peripheral blood as stem cell source, female donor for male recipient, and use of ATG/alemtuzumab were associated with increased mortality whereas reduced-intensity conditioning with lower one. Mortality increased with increasing patients‘ age but decreased in the recent cohorts.
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3.
Measurable residual disease status and outcome of transplant in acute myeloid leukemia in second complete remission: a study by the acute leukemia working party of the EBMT
Gilleece, M. H., Shimoni, A., Labopin, M., Robinson, S., Beelen, D., Socié, G., Unal, A., Ganser, A., Vitek, A., Sengeloev, H., et al
Blood cancer journal. 2021;11(5):88
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Editor's Choice
Abstract
Measurable residual disease (MRD) prior to hematopoietic cell transplant (HCT) for acute myeloid leukemia (AML) in first complete morphological remission (CR1) is an independent predictor of outcome, but few studies address CR2. This analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation registry assessed HCT outcomes by declared MRD status in a cohort of 1042 adult patients with AML CR2 at HCT. Patients were transplanted 2006-2016 from human leukocyte antigen (HLA) matched siblings (n?=?719) or HLA 10/10 matched unrelated donors (n?=?293). Conditioning was myeloablative (n?=?610) or reduced-intensity (n?=?432) and 566 patients (54%) had in-vivo T cell depletion. At HCT, 749 patients (72%) were MRD negative (MRD NEG) and 293 (28%) were MRD positive (MRD POS). Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months (P?0.001). Two-year relapse rates were 24% (95% CI, 21-28) and 40% (95% CI, 34-46) in MRD NEG and MRD POS groups (P?0.001), respectively. Leukemia-free survival (LFS) was 57% (53-61) and 46% (40-52%), respectively (P?=?0.001), but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
PICO Summary
Population
Patients with AML who were transplanted in second complete remission (CR2) at transplant (n=1042)
Intervention
Patients who were minimal disease negative (MRD NEG, n=749)
Comparison
Patients who were minimal disease positive (MRD POS, n=293)
Outcome
Time from diagnosis to HCT was longer in MRD NEG than MRD POS patients (18 vs. 16 months). Two-year relapse rates were 24% and 40% in MRD NEG and MRD POS groups, respectively. Leukemia-free survival (LFS) was 57% and 46%, respectively, but there was no difference in terms of overall survival. Prognostic factors for relapse and LFS were MRD NEG status, good risk cytogenetics, and longer time from diagnosis to HCT. In-vivo T cell depletion predicted relapse.
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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., et al
Bone marrow transplantation. 2020
Abstract
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
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5.
Changes in patients population and characteristics of hematopoietic stem cell transplantation for relapsed/refractory Hodgkin lymphoma: an analysis of the Lymphoma Working Party of the EBMT
Sureda, A., Genadieva Stavrik, S., Boumendil, A., Finel, H., Khvedelidze, I., Dietricht, S., Dreger, P., Hermine, O., Kyriakou, C., Robinson, S., et al
Bone marrow transplantation. 2020
Abstract
Indications for autologous (auto-HCT) and allogeneic transplantation (allo-HCT) in relapsed/refractory Hodgkin lymphoma (rrHL) have been long established. The expectation is that long-term outcomes have significantly improved over time with increased experience in these procedures. The objective of this study was to assess whether this is the case and to identify further areas of improvement. A total of 13,639 adult patients receiving an auto-HCT or allo-HCT for rrHL were reported to the European Society for Blood and Marrow Transplantation (EBMT) over a 25-year period. Regarding auto-HCT, recipients are younger, interval between diagnosis and transplant shorter, peripheral blood has become the universal stem cell source and the use of total body irradiation is almost non-existent in recent years. Allo-HCT is currently mostly used as a second transplant; recipients are younger, fitter and less frequently, chemorefractory. Reduced intensity conditioning protocols have vastly replaced myeloablative protocols. Increasing numbers of haplo-HCT have been reported. Both in auto-HCT and allo-HCT, NRM, PFS and OS have significantly improved but relapse remains the main cause of treatment failure. A better selection of patients and improvements in the supportive care has resulted in a reduction in the NRM. Relapse after HCT remains unchanged and further research is needed.
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6.
Influence of donor type, stem cell source and conditioning on outcomes after haploidentical transplant for lymphoma - a LWP-EBMT study
Bazarbachi, A., Boumendil, A., Finel, H., Castagna, L., Dominietto, A., Blaise, D., Diez-Martin, J. L., Tischer, J., Gulbas, Z., Wallet, H. L., et al
British journal of haematology. 2019
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Editor's Choice
Abstract
Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post-transplant cyclophosphamide. Median follow-up of alive patients was 32 months. On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor.
PICO Summary
Population
Adults with lymphoma (n=474) : Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29)
Intervention
Haploidentical transplant with post-transplant cyclophosphamide
Comparison
None
Outcome
On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival was better for FL, HL and PTCL, whereas overall survival was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status.
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7.
Autologous stem cell transplantation for HIV-associated lymphoma in the antiretroviral and rituximab era: a retrospective study by the EBMT Lymphoma Working Party
Hubel, K., Re, A., Boumendil, A., Finel, H., Hentrich, M., Robinson, S., Wyen, C., Michieli, M., Kanfer, E., Diez-Martin, J. L., et al
Bone marrow transplantation. 2019
Abstract
The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.
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8.
Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis
Robin, M., de Wreede, L. C., Wolschke, C., Schetelig, J., Eikema, D. J., Van Lint, M. T., Knelange, N. S., Beelen, D., Brecht, A., Niederwieser, D., et al
Haematologica. 2019
Abstract
Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events occur during the first 2 years and hence we aimed to analyze the outcome of 2-year disease-free survivors. 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, Disease-free survival was 64% (60-68%) and Overall Survival was 74% (71-78%) at 10 years, better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients < 45 years and 33% (13-53%) in patients ≥ 65 years. The main cause of death was relapse of the primary disease. Graft versus Host Disease before 2 years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GVHD prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at 2-years but the occurrence of late complications, including late relapses, infectious complications and secondary malignancies highlights the importance of screening and monitoring of long-term survivors.
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9.
Myeloablative and Reduced-intensity conditioned Allogeneic Haematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of EBMT
McLornan, D., Szydlo, R., Koster, L., Chalandon, Y., Robin, M., Wolschke, C., Beelen, D., Socie, G., Bornhauser, M., Angelucci, E., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
This retrospective study by the EBMT analysed the outcome of 2224 Myelofibrosis patients who underwent allogeneic stem cell transplantation (allo-SCT) between 2000-2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced intensity conditioning (RIC). Median patient age was 52.9 years (r, 18-74) and 57.5 years (range(r), 21-76) in the MAC and RIC cohorts respectively. Donor type was similar: matched sibling donors (MAC- 317 (41%)) and RIC- 552 (38%) and unrelated donors (UD; MAC (464 (59%); RIC- 891 (62%)). Median time to both neutrophil and platelet (>20x10(9)/L) engraftment did not differ between cohorts. Rates of grade II-IV acute (a) GVHD were 28% (MAC) and 31% (RIC; (p=ns). Cumulative cGVHD rates (limited/ extensive) were 22%/27% (MAC) and 19%/ 31% (RIC; p=0.10). Cumulative incidences of Non-relapse mortality (NRM) at 1, 3 and 5-years were: 25.5%, 32.2% and 34.6% (MAC) and 26.3%, 32.8% and 34.4% (RIC). There was a trend towards a higher relapse rate with RIC regimens compared to MAC (p=0.08); rates at 1, 3 and 5-years were: 10.9%, 17.2% and 20.1% (MAC) and 14%, 19.7% and 23.2% (RIC), respectively. No significant difference in 5yr probabilities of overall survival (OS) was noted: MAC 53.0% (95% confidence intervals (CI) 49.1-56.9) and RIC 51.0% (95% CI: 48.3-53.7); p=0.78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI: 29.0-36.1) in the MAC group and 26.1% (95% CI: 23.9-28.2) in the RIC group (p=0.001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 yrs), using an unrelated donor and a Karnofsky Performance Status (KPS) of 80 or less. For the RIC cohort, worse OS and NRM was associated with age 60- 70 years when compared to younger recipients, use of a mismatched donor and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend towards less relapse and an overall suggested advantage of improved GRFS; albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient and optimisation to reduce significant relapse and NRM rates are required.
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10.
Impact of t-cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the european blood and marrow transplant (ebmt) saa working party
Samarasinghe, S., Clesham, K., Iacobelli, S., Sbianchi, G., Knol, C., Hamladji, R. M., Socie, G., Aljurf, M., Koh, M., Sengeloev, H., et al
American journal of hematology. 2018
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Editor's Choice
Abstract
We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) haemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either ATG (n=1283), alemtuzumab (n=261) or no serotherapy (NS) (n=293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared to no serotherapy (p=0.021 and p=0.003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared to ATG (P=0.012) and no serotherapy (p < 0.001). By multivariate analysis, when compared to ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14-0.47; p<0.001) and chronic GVHD (HR 0.58; 95% CI 0.35 - 0.94; p=0.027). OS was significantly better in ATG and alemtuzumab patients compared with no serotherapy (p=0.010 and p=0.025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared to ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA. This article is protected by copyright. All rights reserved.