-
1.
Allogeneic stem cell transplant recipients surviving at least 2 years without relapse: outcome and risk factors
Grønvold, B. L., Ali, M. M., Myklebust, TÅ, Lenartova, A., Remberger, M., Abrahamsen, I. W., Tjønnfjord, G. E., Myhre, A. E., Fløisand, Y., Gedde-Dahl, T.
EJHaem. 2024;5(1):117-124
Abstract
Outcomes of 2-year survivours undergoing allo-haematopoietic stem cell transplantation at Oslo University Hospital were retrospectively assessed with the objectives of identification of risk factors for late death as possible means for precautionary measures and interventions to improve long-term survival. 421 patients with haematological malignancy, transplanted between 2005 and 2019, alive and free of disease after 2 years were included with data reported from The OUS-HSCT registry. Median follow-up was 6.2 years (2.016.1), and 232 patients (55%) were observed for minimum 5 years. The probability of being alive 5 and 10 years after HSCT was 86% and 76%. Primary risk factors for late death included initial diagnosis of age ≥ 60 years, chronic lymphocytic leukaemia (CLL), previous blood stream- or invasive fungal infection (BSI, IFI), and chronic graft-versus-host disease (cGVHD). Transplant-related mortality (TRM) and relapse at 5 years were 9.0% and 7.7%, respectively. Two factors were associated with the latter: cytomegalovirus (CMV) seronegative donor and CLL. Compared with the age- and gender-matched Norwegian general population, life expectancy was lower for each disease, except for CML. The prospect for the long-term survival is good for 2-year survivors of the allogeneic hematopoietic stem cell transplantation. However, life expectancy remains inferior to the age- and gender-matched general population. Optimising prophylaxis and treatment for chronic GVHD, BSI and IFI are needed along with the improved adherence to guidelines for early detection of secondary malignancies. Measures to improve immune reconstitution, possibly the microbiota, and the use of CMV seropositive donors regardless of recipient sero-status may be warranted and should be addressed in further studies.
-
2.
Cardiovascular Risk Stratification of Patients Undergoing Hematopoietic Stem Cell Transplantation: The CARE-BMT Risk Score
Vasbinder, A., Catalan, T., Anderson, E., Chu, C., Kotzin, M., Murphy, D., Cheplowitz, H., Diaz, K. M., Bitterman, B., Pizzo, I., et al
Journal of the American Heart Association. 2024;13(1):e033599
Abstract
BACKGROUND Evidence guiding the pre-hematopoietic stem cell transplantation (HSCT) cardiovascular evaluation is limited. We sought to derive and validate a pre-HSCT score for the cardiovascular risk stratification of HSCT candidates. METHODS AND RESULTS We leveraged the CARE-BMT (Cardiovascular Registry in Bone Marrow Transplantation) study, a contemporary multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019 (N=2435; mean age at transplant of 55 years; 4.9% Black). We identified the subset of variables most predictive of post-HSCT cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, heart failure, stroke, atrial fibrillation or flutter, and sustained ventricular tachycardia. We then developed a point-based risk score using the hazard ratios obtained from Cox proportional hazards modeling. The score was externally validated in a separate cohort of 919 HSCT recipients (mean age at transplant 54 years; 20.4% Black). The risk score included age, transplant type, race, coronary artery disease, heart failure, peripheral artery disease, creatinine, triglycerides, and prior anthracycline dose. Risk scores were grouped as low-, intermediate-, and high-risk, with the 5-year cumulative incidence of cardiovascular events being 4.0%, 10.3%, and 22.4%, respectively. The area under the receiver operating curves for predicting cardiovascular events at 100 days, 5 and 10 years post-HSCT were 0.65 (95% CI, 0.59-0.70), 0.73 (95% CI, 0.69-0.76), and 0.76 (95% CI, 0.69-0.81), respectively. The model performed equally well in autologous and allogeneic recipients, as well as in the validation cohort. CONCLUSIONS The CARE-BMT risk score is easy to calculate and could help guide referrals of high-risk HSCT recipients to cardiovascular specialists before transplant and guide long-term monitoring.
-
3.
Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry
Lacan, C., Lambert, J., Forcade, E., Robin, M., Chevallier, P., Loron, S., Bulabois, CÉ, Orvain, C., Ceballos, P., Daguindau, E., et al
Journal of hematology & oncology. 2024;17(1):2
Abstract
The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II-IV and III-IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III-IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II-IV; 16% for aGVHD III-IV) than with BM (28% for aGVHD II-IV; 8% for aGVHD III-IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III-IV remained higher with PB than with BM graft (HR = 2.0; range [1.17-3.43], p = 0.012).
-
4.
Outcomes of CMML patients undergoing allo-HCT are significantly worse compared to MDS-a study of the CMWP of the EBMT
Rovó, A., Gras, L., Piepenbroek, B., Kröger, N., Reinhardt, H. C., Radujkovic, A., Blaise, D., Kobbe, G., Niityvuopio, R., Platzbecker, U., et al
American journal of hematology. 2024;99(2):203-215
-
-
Free full text
-
Abstract
Although CMML since long has been separated from MDS, many studies continue to evaluate the outcomes of both diseases after hematopoietic cell transplantation (allo-HCT) together. Data evaluating outcomes of a large CMML cohort after allo-HCT compared to MDS are limited. We aim to compare outcomes of CMML to MDS patients who underwent allo-HCT between 2010 and 2018. Patients ≥18 years with CMML and MDS undergoing allo-HCT reported to the EBMT registry were analyzed. Progression to AML before allo-HCT was an exclusion criterion. Overall survival (OS), progression/relapse-free survival (PFS), relapse incidence (including progression) (REL), and non-relapse mortality (NRM) were evaluated in univariable and multivariable (MVA) Cox proportional hazard models including interaction terms between disease and confounders. In total, 10832 patients who underwent allo-HCT were included in the study, there were a total of 1466 CMML, and 9366 MDS. The median age at time of allo-HCT in CMML (median 60.5, IQR 54.3-65.2 years) was significantly higher than in the MDS cohort (median 58.8, IQR 50.2-64.5 years; p < .001). A significantly higher percentage of CMML patients were male (69.4%) compared to MDS (61.2%; p < .001). There were no clinically meaningful differences in the distribution of Karnofsky score, Sorror HCT-CI score at allo-HCT, and donor type, between the CMML and MDS patients. RIC platforms were utilized in 63.9% of CMML allo-HCT, and in 61.4% of MDS patients (p = .08). In univariable analyses, we found that OS, PFS, and REL were significantly worse in CMML when compared with MDS (all p < .0001), whereas no significant difference was observed in NRM (p = .77). In multivariable analyses, the HR comparing MDS versus CMML for OS was 0.81 (95% CI, 0.74-0.88, p < .001), PFS 0.76 (95% CI 0.70-0.82, p < .001), relapse 0.66 (95% CI 0.59-0.74, p < .001), and NRM 0.87 (95% CI 0.78-0.98, p = .02), respectively. The association between baseline variables and outcome was found to be similar in MDS and CMML (all interaction p > .05) except for a decreasing trend over time of the risk of relapse in CMML (HR allo-HCT per year later 0.94, 95% CI 0.90-0.98), whereas no such trend was observed in MDS (HR 1.00, 95% CI 0.98-1.02). The poor outcome observed for CMML could be related to variables not measured in this study or to factors inherent to the disease itself. This study demonstrates that outcomes of CMML patients after allo-HCT are significantly worse compared to MDS. The results of this study may contribute to future recommendations for allo-HCT in CMML patients.
-
5.
The outcome and predictive model of allogeneic hematopoietic stem cell transplantation among elderly patients with severe aplastic anemia from the Chinese Blood and Marrow Transplant Registry Group
Xu, Z. L., Xu, L. P., Zhang, Y. C., Zhou, Y. H., Jiang, E. L., Zhang, J. P., Fu, B., Ouyang, G. F., Song, X. M., Zhang, X. J., et al
Haematologica. 2024
Abstract
Not available.
-
6.
SERIOUS STEM CELL DONATION EVENTS AND RECIPIENT ADVERSE REACTIONS RELATED TO SARS-CoV-2: REVIEW OF REPORTS TO THE WORLD MARROW DONOR ASSOCIATION
Pawson, R., Anthias, C., Cody, M., Fechter, M., Fournier, D., O'Flaherty, E., Oliviera, D., van Eerden, E., Mengling, T.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND The SARS-CoV-2 pandemic has deeply impacted hematopoietic stem cell (HSC) donations and transplants. Many changes in practice have been introduced and it is vital to monitor the impact of these on donations and transplants. As part of a global response to this pandemic, the World Marrow Donor Association (WMDA) asked that its member registries and cord blood banks submit SARS-CoV-2-related adverse events to the WMDA-operated Serious Product Events and Adverse Reactions (SPEAR) database. OBJECTIVE This article reviews SARS-CoV-2-related SPEARs that occurred in 2020. STUDY DESIGN The WMDA Serious Product Events and Adverse Reactions (SPEAR) Committee reviewed reports submitted via an online tool. The Committee reviewed each report following the EU definitions of a serious adverse event or reaction and determined the imputability and its impact. Reports submitted in 2020 were included in this analysis RESULTS 74 such reports were received and were classified as: donor-related 41 (55.4%); recipient-related 3 (4.1%); technical issues 31 (41.8%) transport-related issues 4 (5.4%). Five cases appeared in more than one category. The commonest adverse events reported were of cells being unused. Many of these cases were caused by the uncoupling of the donation and transplant consequent on the cryopreservation of products as well as technical issues related to cell viability. Experience in some registries suggests these issues have become less frequent as transplant centres have become used to the changes in practice. CONCLUSION Lessons learnt include the importance of confirming recipient eligibility before the donors starts mobilisation or collection and minimising the time from collection of cells to transplant. Transplant centres should familiarise themselves with the expected cell losses when PBSC and BM products are cryopreserved and have validated viability assays for quality assurance. Reassuringly there were no reports of donors becoming severely unwell because of G-CSF or of transmission of SARS-CoV-2 to recipients and only one report of complete failure of transport of a donation.
-
7.
Impact of Second Primary Malignancy Post-Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis
Ragon, B. K., Shah, M. V., D'Souza, A., Estrada-Merly, N., Gowda, L., George, G., DeLima, M., Hashmi, S., Kharfan-Dabaja, M. A., Majhail, N. S., et al
Blood advances. 2023
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials employing auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in MM patients following auto-HSCT using CIBMTR registry data. Adult MM patients who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n=3,948). At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62, P<.001 and HR 5.01, P<.001, respectively) and OS (HR 3.85, P<.001 and HR 8.13, P<.001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in MM patients and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT.
PICO Summary
Population
Drawn from the CIBMTR registry, adults with multiple myeloma (MM) who underwent first auto-HSCT with melphalan conditioning regimen and received maintenance therapy (n=3,948)
Intervention
Identification of second primary malignancies (SPM) or second haematological malignancies (SHM) following HSCT.
Comparison
None
Outcome
At a median follow up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (HR 2.62 and HR 5.01 respectively) and OS (HR 3.85, and HR 8.13, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% versus 30% and 53% versus 18%, respectively).
-
8.
Non-T-depleted haploidentical transplantation with post-transplant cyclophosphamide in patients with secondary versus de novo AML in first complete remission: a study from the ALWP/EBMT
Nagler, A., Labopin, M., Blaise, D., Raiola, A. M., Corral, L. L., Bramanti, S., Sica, S., Kwon, M., Koc, Y., Pavlu, J., et al
Journal of hematology & oncology. 2023;16(1):58
Abstract
We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p < 0.0001, had better transplantation comorbidity index (HCT-CI) ≥ 3 21.3% versus 40.8%, p < 0.0001 and Karnofsky performance status (KPS) with KPS ≥ 90 in 78% versus 68.5%, respectively, p = 0.002. The two patient groups did not differ with respect to gender, cytomegalovirus serostatus, and cell source. Median time from diagnosis to HaploSCT was 5.2 versus 4.9 months, respectively, p = 0.005. Fewer sAML patients received myeloablative conditioning 35.1% versus 50.1%, p < 0.0001. Two hundred and eleven sAML and 410 de novo AML patients were included in the matched-pair analysis matching two de novo AML with each sAML. No significant difference was observed in any transplantation outcome parameter between the sAML versus de novo AML groups. Two-year non-relapse mortality and relapse incidence did not differ with HaploSCT for de novo versus sAML; 21.4% versus 21%, hazard ratio (HR) = 0.98, p = 0.9 and 23.4% versus 20.6%, HR = 0.92, p = 0.67, respectively. Two-year leukemia-free survival, overall survival, and graft-versus-host disease (GVHD)-free, relapse-free survival were also not different between the de novo AML and sAML groups 55.2% versus 58.4%, HR = 0.95, p = 0.67; 61.4% versus 66.4%, HR = 0.91, p = 0.51 and 46.3% versus 48.2%, HR = 0.92, p = 0.48, respectively. Similarly, the incidence of engraftment as well as acute and chronic GVHD was similar between the 2 cohorts. In conclusion, HaploSCT with PTCy may be able to overcome the bad prognosis of sAML as results are not significantly different to those of HaploSCT in de novo AML.
-
9.
Outcomes in human T-cell leukemia virus type I carriers after hematopoietic stem cell transplantation for diseases other than adult T cell leukemia/lymphoma: a Japanese national survey
Nakano, N., Nakasone, H., Fuji, S., Shinohara, A., Suzuki, R., Utsunomiya, A., Eto, T., Morishima, S., Ikegame, K., Kakinoki, Y., et al
The Lancet regional health. Western Pacific. 2023;40:100902
Abstract
BACKGROUND Human T-cell leukemia virus type I (HTLV-1) is a retrovirus known to cause adult T-cell leukemia/lymphoma (ATL). There are few reports on hematopoietic stem cell transplantation (HSCT) for HTLV-1 carriers with diseases other than ATL. METHODS A total of 25,839 patients (24,399 adults and 1440 children) with pre-transplant HTLV-1 serostatus information recorded in the Japanese National Survey Database who had undergone their first HSCT were analyzed. We investigated the overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM) after HSCT in relation to HTLV-1 serologic status. FINDINGS Three hundred and forty-eight patients were HTLV-1 antibody carriers. The number of HTLV-1 carriers and noncarriers among adult patients who received allogeneic HSCT (allo-HSCT) or autologous HSCT (auto-HSCT) was 237/15,777 and 95/8920, respectively, and was 16/1424 among pediatric patients who received allo-HSCT. No pediatric HTLV-1 carrier recipients undergoing auto-HSCT were identified. There were no significant differences between HTLV-1 carriers and non-carriers regarding stem cell source, disease risk, or HCT-CI score prior to allo-HSCT. Multivariate analysis of OS (P = 0.020) and TRM (P = 0.017) in adult patients showed that HTLV-1 positive status was a significant prognostic factor. In children, TRM was significantly higher (P = 0.019), but OS was not significantly different. In adult patients who underwent auto-HSCT, HTLV-1 positive status was not a significant prognostic factor. In adult allo-HSCT patients, cytomegalovirus reactivation was significantly more common in HTLV-1 carriers (P = 0.001). INTERPRETATION HTLV-1 antibody positivity was shown to have a poor prognosis in OS and TRM after allo-HSCT in adult patients and in TRM after allo-HSCT in pediatric patients. FUNDING This work was supported in part by the practical research programs of the Japan Agency for Medical Research and Development (AMED) under grant number 17ck0106342h0001.
-
10.
Allogeneic hematopoietic stem cell transplantation in patients aged 60-79 years in Germany (1998-2018): a registry study
Weller, J. F., Lengerke, C., Finke, J., Schetelig, J., Platzbecker, U., Einsele, H., Schroeder, T., Faul, C., Stelljes, M., Dreger, P., et al
Haematologica. 2023
-
-
-
Free full text
-
Editor's Choice
Abstract
Incidences of diseases treated with transplantation frequently peak at higher age. The contribution of age to total risk of transplantation has not been estimated amidst an aging society. We compare outcomes of 1,547 patients aged 70-79 and 9,422 patients aged 60-69 transplanted 1998-2018 for myeloid, lymphoid and further neoplasia in Germany. To quantify the contribution of population mortality to survival, we derive excess mortality based on a sex-, year- and age-matched German population in a multistate model that incorporates relapse and graft-versus-host-disease (GvHD). Overall, relapse-free (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients 70-79, compared to patients 60-69, with 36% [95%CI 34-39%] versus 43% [41-44%], 32% [30-35%] versus 36% [35-37%] and 23% [21-26%] versus 27% [26-28%] three years post-transplant (p<0.001). Cumulative incidences of relapse at three years are 27% [25-30%] (patients 70-79) versus 29% [29-30%] (60-69, p=0.71), yet the difference in non-relapse mortality (NRM, 40% [38-43%] versus 35% [34-36%] in 70-79 versus 60-69 aged patients, p<0.001) translates into survival differences. Median OS of patients surviving >1 year relapse-free is 6.7 (median, 95%CI 4.5-9.4, 70-79) versus 9 (8.4-10.1, 60-69) years since landmark. Three years after RFS of 1 year, excess NRM is 14% [95%CI 12-18%] in 70-79 versus 12% [11-13%] in 60-69, while population NRM is 7% [6-7%] versus 3% [3-3%]. Mortality for reasons other than relapse, GvHD or age is as high as 27% [24-29%] and 22% [22-23%] 4 years after transplantation. In conclusion, survival amongst older patients is adequate after allogeneic stem cell transplantation.
PICO Summary
Population
Adults aged 60 years and over, receiving first allogeneic transplant for any malignant disease, identified from the German registry for stem cell transplantation (n=10,969)
Intervention
Transplant aged 70-79 years (n=1,547)
Comparison
Transplant aged 60-69 years (n=9,422)
Outcome
Overall, relapse-free (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients 70-79, compared to patients 60-69, with 36% [95%CI 34-39%] versus 43% [41-44%], 32% [30-35%] versus 36% [35-37%] and 23% [21-26%] versus 27% [26-28%] three years post-transplant. Cumulative incidences of relapse at three years are 27% [25-30%] (patients 70-79) versus 29% [29-30%] (60-69), yet the difference in non-relapse mortality (NRM, 40% [38-43%] versus 35% [34-36%] in 70-79 versus 60-69 aged patients translates into survival differences. Median OS of patients surviving >1 year relapse-free is 6.7 (median, 95%CI 4.5-9.4, 70-79) versus 9 (8.4-10.1, 60-69) years since landmark. Three years after RFS of 1 year, excess NRM is 14% [95%CI 12-18%] in 70-79 versus 12% [11-13%] in 60-69, while population NRM is 7% [6-7%] versus 3% [3-3%]. Mortality for reasons other than relapse, GvHD or age is as high as 27% [24-29%] and 22% [22-23%] 4 years after transplantation.