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).

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.

Allogeneic hematopoietic cell transplantation in patients with therapy-related myeloid neoplasm after breast cancer: a study of the Chronic Malignancies Working Party of the EBMT.

We performed a registry study on therapy-related myeloid neoplasm (t-MN), both therapy-related myelodysplastic syndrome (t-MDS) and acute myeloid leukemia (t-AML) following treatment for breast cancer who underwent a first allogeneic hematopoietic cell transplant (allo-HCT). Of 252 identified female patients (median age 57 years), 77% were transplanted for t-AML and 23% for t-MDS, with a median time from breast cancer diagnosis to the diagnosis of tMN and subsequent allo-HCT of 3.7 and 4.6 years, respectively. At transplant, 191 patients were in remission for breast cancer, while 4 were not (57 missing). T-MN was in a complete remission at the time of transplant in 67% of patients. 2-year overall survival, relapse free-survival, relapse incidence and non-relapse mortality were 50%, 45%, 33%, and 22%, respectively. Multivariable analysis revealed that if the t-MN was not in CR pre-transplant, this was associated with lower OS, RFS, and a higher relapse incidence. Seventeen cases of breast cancer recurrence were recorded after a median of 2.4 years post-transplant, and relapse of primary breast cancer accounted for 7% of deaths. This study indicates that allo-HCT for t-MN following treatment for breast cancer shows encouraging transplant outcomes. The incidence of breast cancer relapse post-transplant remains a cause for concern.

COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey.

This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.

Hematopoietic stem cell transplantation for adults with relapsed acute promyelocytic leukemia in second complete remission.

We retrospectively compared outcomes of a large series of adult patients with APL in CR2 receiving alloHSCT (n = 228) or autoHSCT (n = 341) reported to the European Society for Blood and Marrow Transplantation from January 2004 to December 2018. The 2-year cumulative incidence of non-relapse mortality was significantly higher for alloHSCT 17.3% (95% CI 12.5-22.8) compared with autoHSCT 2.7% (95% CI 1.2-5) (p = 0.001), while differences in relapse rate were not significant (28% versus 22.9%; p = 0.28). Leukemia-free survival (LFS) and overall survival (OS) favored autoHSCT with 74.5% (95% CI 69-79.2) and 82.4% (95% CI 77.3-86.5) compared with alloHSCT with 54.7% (95% CI 47.5-61.3) (p = 0.001) and 64.3% (95% CI 57.2-70.6), respectively (p = 0.001 and p = 0.001). Multivariable analysis showed significantly worse LFS after alloHSCT (HR 0.49; 95% CI 0.37-0.67; p < 0.0001), older age (p = 0.001), and shorter time from diagnosis to transplant (p = 0.00015). Similar results were obtained for OS. The study shows that autoHSCT resulted in better survival outcomes (LFS and OS) for APL in CR2. These results were mainly due to reduced NRM in the autoHSCT as compared to alloHSCT.

Tandem Autologous Stem Cell Transplantation Improves Outcomes in Newly Diagnosed Multiple Myeloma with Extramedullary Disease and High-Risk Cytogenetics: A Study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

Although high-dose therapy and autologous stem cell transplant combined with novel agents continues to be the hallmark of first-line treatment in newly diagnosed transplant-eligible multiple myeloma patients, the impact of tandem autologous or autologous/reduced-intensity allogeneic transplant for patients with extramedullary disease (EMD) and high-risk cytogenetics is not yet defined. Here, we analyzed clinical and cytogenetic data from 488 adult myeloma patients with EMD undergoing single autologous (n = 373), tandem autologous (n = 84), or autologous-allogeneic transplant (n = 31) between 2003 and 2015. At least 1 high-risk abnormality was present in 41% (n = 202), with del(17p) (40%) and t(4;14) (45%) the most frequent. More than 1 high-risk abnormality was found in 54%. High-risk cytogenetics showed worse 4-year overall survival (OS) and progression-free survival (PFS) of 54% and 29%, respectively, versus 78% and 49% for standard-risk cytogenetics (P < .001). Co-segregation of high-risk abnormalities did not seem to affect outcome. Regarding transplant regimen, OS and PFS were 70% and 43% for single autologous versus 83% and 52% for tandem autologous and 88% and 58% for autologous-allogeneic (P = .06 and P = .30). In multivariate analysis high-risk cytogenetics were associated with worse survival (hazard ratio [HR], 2.00; P = .003), whereas tandem autologous significantly improved outcome versus single autologous transplant (HRs, .46 and .64; P = .02 and P = .03). Autologous-allogeneic transplant did not significantly differ in outcome but appeared to improve survival, but results were limited because of small population (HR, .31). In conclusion, high-risk cytogenetics is frequently observed in newly diagnosed myeloma with EMD and significantly worsens outcome after single autologous, whereas a tandem autologous transplant strategy may overcome onset poor prognosis.

Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies.

Respiratory viruses (RVs) are known to be major causes of morbidity and mortality in recipients of hematopoietic stem cell transplants (HSCTs), but prospective long-term studies are lacking. We prospectively screened all adult HSCT recipients (172 allogeneic [alloHSCT] and 240 autologous [autoHSCT]) who underwent transplantation during a 4-year period (1999 to 2003) for the development of a first episode of symptomatic upper respiratory tract infections and/or lower respiratory tract infections (LRTI) by an RV. RVs studied were influenza A and B viruses (n=39), human respiratory syncytial virus (n=19), human adenoviruses (n=11), human parainfluenza viruses 1 to 3 (n=8), human enteroviruses (n=5), human rhinoviruses (n=3), and the recently discovered human metapneumoviruses (n=19). During the study, 51 and 32 cases of RV symptomatic infections were identified of alloHSCT and autoHSCT recipients (2-year incidence, 29% and 14%, respectively). Risk factors for progression of upper respiratory tract infection to LRTI included severe (<0.2x10(9)/L) and moderate (<0.2x10(9)/L) lymphocytopenia in alloHSCT (P=.02) and autoHSCT (P=.03). Death from LRTI was attributed to an RV in 8 alloHSCT recipients. Symptomatic RV had no effect on 2-year outcomes, with the possible exception of influenza A and B virus infections in autoHSCT: these were associated with nonrelapse mortality (P=.02). In conclusion, this prospective trial allows an estimation of the minimum incidence of a first RV infection in adult HSCT recipients and identifies risk factors for acquisition of an RV infection and progression to LRTI; this should aid in the design of future studies. In addition, human metapneumovirus should be added to the potentially serious causes of RV infections in HSCT.