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1.
Splenic irradiation for myelofibrosis prior to hematopoietic cell transplantation: A global collaborative analysis
Gagelmann, N., Hobbs, G. S., Campodonico, E., Helbig, G., Novak, P., Schroeder, T., Schneider, A., Rautenberg, C., Reinhardt, H. C., Bosques, L., et al
American journal of hematology. 2024
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Editor's Choice
Abstract
Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field. Here, we leveraged a global collaboration to investigate the safety and efficacy of splenic irradiation as part of the HCT platform for patients with myelofibrosis. We included 59 patients, receiving irradiation within a median of 2 weeks (range, 0.9-12 weeks) before HCT. Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse (p = .01), showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy. In conclusion, splenic irradiation immediately before HCT is a reasonable approach in patients experiencing JAK inhibition failure and is associated with a low incidence of relapse.
PICO Summary
Population
Adults with with primary myelofibrosis, post polycythemia vera, and post-essential thrombocythemia myelofibrosis, identified from centres worldwide (n=171)
Intervention
Splenic irradiation within a median of 2 weeks before transplant (n=59)
Comparison
Matched controls receiving immediate transplant without splenic irradiation (n=56), or who had splenectomy (n=56)
Outcome
Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse, showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy.
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2.
Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102
Saber, W., Bansal, A., Li, L., Scott, B. L., Sangaralingham, L. R., Thao, V., Roth, J. A., Wright, W., Steuten, L. M. G., Pidala, J. A., et al
JCO oncology practice. 2024;:Op2300413
Abstract
PURPOSE BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial. METHODS Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities. RESULTS Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY. CONCLUSION Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.
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3.
Comparison of melphalan dose in patients with myelodysplastic syndrome undergoing allogeneic transplantation with reduced-intensity conditioning
Kurosawa, S., Shimomura, Y., Itonaga, H., Katayama, Y., Onizuka, M., Tanaka, M., Kobayashi, H., Ozawa, Y., Sawa, M., Kanda, J., et al
Transplantation and cellular therapy. 2024
Abstract
The present study compared lower-dose melphalan (80 mg/m(2), FM80) and higher-dose melphalan (140 mg/m(2), FM140) when administering reduced-intensity conditioning with fludarabine in adult patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data (2006-2019) and compared transplant outcomes between the two groups. Ninety-two patients (median age, 61 [interquartile range, 56-65] years) were assigned to the FM80 and FM140 groups by propensity score matching. The 3-year overall survival (OS) rate in the FM140 group (63.9%; 95% confidence interval [CI], 52.9-73.0%) was significantly higher than that in the FM80 group (54.2%; 95% CI, 37.1-52.1%) (P = 0.038). The FM140 group had a non-significantly (P = 0.095) lower 3-year cumulative incidence of relapse (15.5%; 95% CI, 8.9-23.8% versus 26.0%; 95% CI, 17.3-35.5%). The 3-year cumulative incidences of non-relapse mortality were 22.3% (95% CI, 14.1-31.8%) and 23.7% (95% CI, 15.4-33.2%) in the FM80 and FM140 groups, respectively (P = 0.49). The beneficial effect of FM140 was more evident in patients with a poor cytogenetic risk. Our findings suggest the superiority of FM140 in patients with MDS undergoing allo-HSCT, especially in high-risk patients.
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4.
Sequential haplo-identical conditioning transplant regimen for pediatric patients with relapsed or refractory hemophagocytic lymphohistiocytosis
Yue, Y., Fan, S., Liu, Z., Jiang, F., Chen, J., Qin, J., Sun, Y.
Bone marrow transplantation. 2024
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) currently stands as the sole remedy for individuals afflicted with hemophagocytic lymphohistiocytosis (HLH). In this study, we retrospectively evaluated how pediatric patients with relapsed or refractory (R/R) HLH responded to our institution's cocktail conditioning regimen. The disease was diagnosed according to criteria applicable to patients with familial/genetic, relapsing, or severe/persistent HLH. All donors were HLA haplo-identical family donors. In our cohort, sixty-five patients (P-HLH), including 28 with familial/genetic HLH, 36 with secondary HLH, and 1 with an unknown cause, underwent haplo-identical family donor HSCT. The conditioning regimen consisted of intravenous administration of etoposide (VP-16), busulfan, fludarabine, rabbit anti-human thymocyte globulin (r-ATG), and cyclophosphamide (Cy). Tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GvHD) prevention. We observed that the median time for neutrophil recovery was 11 days (range, 8-24), and for platelet counts to exceed 20 × 10(9)/L, it was 14 days (range, 7-130). There were 5 patients (7.7%) who experienced grades III to IV acute GvHD, and 6 patients (9.2%) developed extensive chronic GvHD. The estimated 3- and 5-year overall survival rates were 78.1% (95% CI, 65.8-84.6%) and 74.9% (95% CI, 61.2-84.4%), respectively. The estimated 3- and 5-year event-free survival rates were 73.5% (95% CI, 60.8-82.6%) and 70.3% (95% CI, 56.4-80.5%), respectively. Our findings demonstrate that our innovative conditioning regimen is both effective and safe, offering valuable insights for healthcare professionals evaluating the merits of existing therapies.
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5.
Finding a balance in reduced toxicity hematopoietic stem cell transplantation for thalassemia: role of infused CD3+ cell count and immunosuppression
Meissner, B., Lang, P., Bader, P., Hoenig, M., Müller, I., Meisel, R., Greil, J., Sauer, M. G., Metzler, M., Corbacioglu, S., et al
Bone marrow transplantation. 2024
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Full text
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Editor's Choice
Abstract
We performed a retrospective analysis on 124 patients with transfusion-dependent thalassemia who were registered in the German pediatric registry for stem cell transplantation. All patients underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 2011 and 2020 and belonged mainly to Pesaro risk class 1-2. Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% (P = 0.763) and 96.9% ± 3.1% (P = 0.155) after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3% (P = 0.029); TFS: 79.9% ± 7.4% (P = 0.082)). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 10(7)/kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses. Taken together, this information might be used to develop more risk-adapted HSCT regimens for thalassemia patients.
PICO Summary
Population
Children and young adults with transfusion-dependent thalassemia who underwent first allogeneic transplant between 2011 and 2020 and were registered in the German pediatric registry for stem cell transplantation. (n=124)
Intervention
Treosulfan-fludarabine-thiotepa based conditioning (n=92)
Comparison
Busulfan-fludarabine-based conditioning (n=32)
Outcome
Four-year overall (OS) and thalassemia-free survival (TFS) were 94.5% ± 2.9% and 88.0% ± 3.4% after treosulfan-fludarabine-thiotepa- and 96.9% ± 3.1% and 96.9% ± 3.1% after busulfan-fludarabine-based conditioning. Mixed chimerism below 75% occurred predominantly in treosulfan-based regimens (27.5% versus 6.2%). OS and TFS did not differ significantly between matched sibling, other matched family and matched unrelated donor (UD) HSCTs (OS: 100.0%, 100.0%, 96.3% ± 3.6%; TFS: 96.5% ± 2.4%, 90.0% ± 9.5%, 88.9% ± 6.0%). However, mismatched UD-HSCTs performed less favorable (OS: 84.7% ± 7.3%; TFS: 79.9% ± 7.4%). We generated a scoring system reflecting the risk to develop mixed chimerism in our cohort. The main risk-reducing factors were a high CD3+ cell count (≥6 × 10(7)/kg) in the graft, busulfan-conditioning, pre-conditioning therapy and low-targeted ciclosporin A trough levels. Acute GvHD grade III-IV in treosulfan-based concepts predominantly occurred in patients with UD and reduced GvHD prophylaxis but not in the context of high CD3+ cell doses.
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6.
Alemtuzumab and CXCL9 levels predict likelihood of sustained engraftment after reduced-intensity conditioning HCT
Geerlinks, A. V., Scull, B., Krupski, C., Fleischmann, R., Pulsipher, M. A., Eapen, M., Connelly, J. A., Bollard, C. M., Pai, S. Y., Duncan, C. N., et al
Blood advances. 2023;7(14):3725-3734
Abstract
Overall survival after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) using alemtuzumab, fludarabine, and melphalan is associated with high rates of mixed chimerism (MC) and secondary graft failure (GF). We hypothesized that peritransplantation alemtuzumab levels or specific patterns of inflammation would predict these risks. We assessed samples from the Bone Marrow Transplant Clinical Trials Network 1204 (NCT01998633) to study the impact of alemtuzumab levels and cytokine patterns on MC and impending or established secondary GF (defined as donor chimerism <5% after initial engraftment and/or requirement of cellular intervention). Thirty-three patients with hemophagocytic lymphohistiocytosis (n = 25) and other IEIs (n = 8) who underwent HCTs with T-cell-replete grafts were included. Patients with day 0 alemtuzumab levels ≤0.32 μg/mL had a markedly lower incidence of MC, 14.3%, vs 90.9% in patients with levels >0.32 μg/mL (P = .008). Impending or established secondary GF was only observed in patients with day 0 alemtuzumab levels >0.32 μg/mL (P = .08). Unexpectedly, patients with impending or established secondary GF had lower CXCL9 levels. The cumulative incidence of impending or established secondary GF in patients with a day 14+ CXCL9 level ≤2394 pg/mL (day 14+ median) was 73.6% vs 0% in patients with a level >2394 pg/mL (P = .002). CXCL9 levels inversely correlated with alemtuzumab levels. These data suggest a model in which higher levels of alemtuzumab at day 0 deplete donor T cells, inhibit the graft-versus-marrow reaction (thereby suppressing CXCL9 levels), and adversely affect sustained engraftment in the nonmyeloablative HCT setting. This trial was registered at www.clinicaltrials.gov as #NCT01998633.
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7.
Sequential vs myeloablative vs reduced intensity conditioning for patients with myelodysplastic syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: a retrospective study by the chronic malignancies working party of the EBMT
Potter, V., Gras, L., Koster, L., Kroger, N., Sockel, K., Ganser, A., Finke, J., Labussiere-Wallet, H., Peffault de Latour, R., Koc, Y., et al
Bone marrow transplantation. 2023
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Full text
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Editor's Choice
Abstract
The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.
PICO Summary
Population
Patients with myelodysplastic syndrome (MDS) with excess of blasts at allo-HCT, identified from the EBMT registry (n=303)
Intervention
Sequential conditioning, where chemotherapy is followed rapidly by transplant (Seq, n=105)
Comparison
Reduced intensity conditioning (RIC, n=158), or myeloablative conditioning (MAC, n=40).
Outcome
Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS and RFS were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes.
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8.
The impact of Treosulfan-based conditioning for inborn errors of immunity: Is dose monitoring crucial?
Ersoy, G. Z., Çipe, F., Fışgın, T., Aksoy, B. A., Öner Ö, B., Hashemi, N., Aydoğdu, S., Erdem, M., Dikme, G., Murat, K., et al
Clinical transplantation. 2023;:e15083
Abstract
INTRODUCTION In children with inborn errors of immunity (IEI) who will receive a hematopoietic stem cell transplant (HSCT) treosulfan-based conditioning is currently preferred. The aim of this study was to investigate early and late outcomes in pediatric IEI patients receiving pre-HSCT treosulfan and to examine the effect of treosulfan dose monitoring on outcomes. METHODS Seventy-three pediatric patients receiving this management between 2015 and 2022 were included. RESULTS Overall survival rate was 80%, and event-free survival was 67.8%. A larger treosulfan dose AUC after first application increased the rate of early toxicity (p = .034) and slowed lymphocyte engraftment (r = .290; p = .030). Underlying disease, treosulfan AUC, donor type, stem cell type, number of immunosuppressive agents, the dose of anti-thymocyte globulin, and post-transplantation cyclophosphamide did not to increase risk of acute graft-versus-host disease. The risk of mixed chimerism (MC) in patients with autoimmune lymphoproliferative syndrome and leukocyte adhesion deficiency were higher than those with severe combined immunodeficiency (p = .021 and p = .014, respectively). The risk of MC was lower in those receiving peripheral blood stem cells (SC) compared with bone marrow derived SC (OR = .204, p = .022). CONCLUSION The AUC of the treosulfan dose was not associated with poorer late outcomes. Treosulfan is an agent that can be used safely in the IEI patient group, level measurement appears essential to identify early toxicities. Prospective studies with more extended follow-up periods are needed.
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9.
[Stem Cell Transplantations for Patients with Fanconi Anemia: An Israeli Tertiary Center Experience]
Even-Or, E., Zaidman, I., Najajreh, M., Avni, B., Grisariu, S., Stepensky, P.
Harefuah. 2023;162(1):9-14
Abstract
INTRODUCTION Fanconi anemia (FA) is a rare genetic syndrome characterized by increased chromosomal breakage, congenital anomalies, bone marrow failure and an increased tendency to develop malignancies. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure and the hematologic malignancies these patients develop. Given the sensitivity of FA patients to chemotherapy and radiation, as to the clinical symptoms of graft versus host disease (GvHD), HSCT in these patients is challenging. Since the mid-nineties, HSCT for FA patients is performed in our center by using the fludarabine based reduced-intensity protocol. AIMS To summarize the results of HSCT for patients with FA using a fludarabine based reduced-intensity conditioning regimen at the Hadassah Medical Center. METHODS This retrospective research is based on the collection and analysis of clinical and laboratory data from the medical records of patients. RESULTS Since June 1996 up till February 2020, 39 patients with FA underwent 43 HSCTs with a fludarabine based protocol at the Hadassah Medical Center. Four patients required a second transplant due to primary engraftment failure. Nine patients (23%) suffered from acute GvHD, four of them severe. Eight patients (20%) developed chronic GvHD, two with an extensive and debilitating disease. Thirty-three (85%) of the patients survived and six died, five shortly after the transplant, and one twenty years later from malignancy. CONCLUSIONS Our results show high survival rates with low rates of engraftment failure and reasonable rates of GvHD. DISCUSSION As of today, there is an effective and safe treatment for patients with FA who require HSCT by using a fludarabine-based reduced-intensity conditioning regimen, with high survival rates and few complications.
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10.
Transplant Outcomes of Myelofibrosis with Busulfan and Fludarabine Myeloablative Conditioning
Joseph, J., Srour, S. A., Milton, D. R., Ramdial, J. L., Saini, N. Y., Olson, A. L., Bashir, Q., Oran, B., Alousi, A. M., Hosing, C., et al
Transplantation and cellular therapy. 2023
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Full text
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Editor's Choice
Abstract
BACKGROUND Outcomes of myelofibrosis with allogeneic stem cell transplantation (allo-SCT) have improved over the past decade and are partly related to advances in supportive treatments and conditioning regimens. Several factors are known to predict transplant outcomes. However, most studies lack homogeneity in the conditioning regimen used, which limits their ability to assess prognostic factors on transplant outcomes. OBJECTIVE We aimed to determine the risk factors that predict transplant outcomes in patients with myelofibrosis who underwent matched or mismatched allo-SCT using a uniform myeloablative conditioning regimen consisting of busulfan and fludarabine with tacrolimus and methotrexate-based graft-versus-host disease prophylaxis. STUDY DESIGN This single-center study included patients with myelofibrosis who underwent allo-SCT with a matched unrelated donor (MUD), matched related donor (MRD), or mismatched unrelated donor (MMUD) and received busulfan and fludarabine conditioning with methotrexate/tacrolimus-based GVHD prophylaxis. RESULTS Sixty-five patients with myelofibrosis met the criteria and were included in the study. At a median follow-up of 35.6 months, the 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and overall survival (OS) for all study patients were 27%, 20%, and 65%, respectively. In a multivariable analysis for CIR, prior use of JAK inhibitors was significantly associated with a decreased risk of relapse (HR [95% CI], 0.33 [0.11-0.99]; p = 0.048). For NRM, HCT-CI (≥3 vs. <3, 10.09 [2.09-48.76]; p=0.004) and donor type (MUD vs. MRD, 5.38 [1.14-25.30]; p=0.033 and MMUD vs. MRD, 10.73 [1.05-109.4]; p=0.045) were associated with an increased risk of mortality. Likewise for OS, HCT-CI (≥3 vs. <3, 3.31 [1.22-8.99]; p = 0.019) and donor type (MMUD vs. MRD, 5.20 [1.35-19.98]; p = 0.016) were significantly associated with inferior survival. Longer time from diagnosis to allo-SCT seemed to confer worse survival but this didn't reach statistical significance (>12 months vs. ≤12 months: NRM, 7.20 [0.96-53.94]; p=0.055 and OS, 2.60 [0.95-7.14]; p=0.06). CONCLUSIONS In a homogenous cohort of myelofibrosis patients uniformly treated with busulfan/fludarabine myeloablative conditioning and methotrexate-based GVHD prophylaxis, we showed that donor choice and HCT-CI are the two strongest predictors for improved survival after allo-SCT.
PICO Summary
Population
People with myelofibrosis who underwent allo-SCT with a matched unrelated donor (MUD), matched related donor (MRD), or mismatched unrelated donor (MMUD) at a single centre in USA (n=176)
Intervention
Cohort for analysis: all who received myeloablative conditioning regimen consisting of busulfan and fludarabine with tacrolimus and methotrexate-based graft-versus-host disease prophylaxis (n=65)
Comparison
None
Outcome
At a median follow-up of 35.6 months, the 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and overall survival (OS) for all study patients were 27%, 20%, and 65%, respectively. In a multivariable analysis for CIR, prior use of JAK inhibitors was significantly associated with a decreased risk of relapse (HR [95% CI], 0.33 [0.11-0.99]). For NRM, HCT-CI (>/=3 vs. <3, 10.09 [2.09-48.76]) and donor type (MUD vs. MRD, 5.38 [1.14-25.30] and MMUD vs. MRD, 10.73 [1.05-109.4]) were associated with an increased risk of mortality. Likewise for OS, HCT-CI (>/=3 vs. <3, 3.31 [1.22-8.99];) and donor type (MMUD vs. MRD, 5.20 [1.35-19.98]) were significantly associated with inferior survival. Longer time from diagnosis to allo-SCT seemed to confer worse survival but this didn't reach statistical significance (>12 months vs. </=12 months: NRM, 7.20 [0.96-53.94] and OS, 2.60 [0.95-7.14]).