Search

Aim: To determine the unmet needs and challenges in management, diagnosis, treatment, follow-up and patient–physician communication in acute leukemia (AL). Materials & methods: The study was based on a modified Delphi approach. A questionnaire including the major potential obstacles was circulated twice among 13 hematologists. Results: The obstacles in AL management were limited access to the novel treatments and genetic tests, limited bed capacity, insufficient level of knowledge among allied health personnel, limited availability of psycho-oncological support and low levels of awareness in the population about the importance of stem cell donation. Conclusion: The challenges in the management of AL are critical to guide the efforts to improve the quality of healthcare delivery and the evidence-based decision making at treatment of AL patients. [ABSTRACT FROM AUTHOR]

Background: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high‐risk acute lymphoblastic leukemia (ALL) lacking a matched donor. Methods: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft‐vs‐host disease (GVHD) prophylaxis in 2010–2020. Results: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19–73) and 38 (18–75) years, respectively (p =.51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T‐cell depletion (anti‐thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p <.0001). Neutrophil (absolute neutrophil count >0.5 × 109/L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81–2.62; p =.21) and HR = 0.81 (95% CI, 0.52–1.28, p =.38), respectively. HRs for leukemia‐free survival, overall survival, and GVHD‐free, relapse‐free survival were respectively, HR = 1.05 (95% CI, 0.73–1.50, p =.8), HR = 1.17 (95% CI, 0.77–1.76, p =.46), and HR = 1.07 (95% CI, 0.78–1.46, p =.7) for haplo compared to MMUD. Acute (a)GVHD grade 2–4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08–2.76, p =.023), whereas aGVHD grade 3–4 and chronic GVHD did not differ significantly between the two transplant groups. Conclusion: Outcomes of MMUD and haplo transplants with PTCy‐based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants. The outcomes of mismatch unrelated and haploidentical transplants in patients with acute lymphocytic leukemia (ALL) in complete remission are similar. The donor pool for patients with ALL who are in need of allogeneic transplantation and do not have a human leukocyte antigen‐compatible donor is, therefore, enlarged. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: The use of haploidentical hematopoietic cell transplantation (haplo‐HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL). METHODS: The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo‐HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018. RESULTS: The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018. Overall, the 2‐year leukemia‐free survival and relapse incidence rates were 56.5% and 21%, respectively. The 100‐day incidence of grade 2 through 4 acute graft‐vs‐host disease (GVHD) was 34.5%. The rates of nonrelapse mortality (NRM) and overall survival (OS) were 22.5% and 64.7%, respectively. Patients who underwent transplantation during 2016 through 2018 experienced improved rates of leukemia‐free survival (64.9% vs 47.3%; P =.019) and OS (75.5% vs 53.5%; P =.006). Patients who underwent transplantation during 2016 through 2018 developed more grade 2 through 4 acute GVHD (42% vs 26.4%; P =.047). The incidence of relapse, GVHD‐free/relapse‐free survival, grade 3 and 4 acute GVHD, chronic GVHD, and extensive chronic GVHD did not differ significantly between groups. In multivariate analysis, more recently transplanted patients had a significantly reduced risk of NRM (hazard ratio, 0.44; 95% CI, 0.22‐0.89; P =.022) and improved OS (hazard ratio, 0.47; 95% CI, 0.26‐0.86; P =.014). A comparable analysis of patients who had acute myeloid leukemia during the same timeframes did not reveal any statistically significant differences in any outcomes. CONCLUSIONS: The outcome of adult patients with ALL who receive posttransplant cyclophosphamide has improved over time, with an impressive 2‐year OS of 75% and, most recently, an NRM rate of only 17%. In patients with acute lymphocytic leukemia who undergo haploidentical transplantation with posttransplantation cyclophosphamide prophylaxis, significant improvements in leukemia‐free survival and survival are observed in more recently transplanted patients. A nonrelapse mortality rate of 17% is reported in recently transplanted patients with acute lymphocytic leukemia who receive posttransplantation cyclophosphamide prophylaxis. [ABSTRACT FROM AUTHOR]

Background: There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods: We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results: Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions: Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy. [ABSTRACT FROM AUTHOR]

Background: Non-T-cell depleted haploidentical hematopoietic stem cell transplantation (HaploSCT) is being increasingly used in acute lymphoblastic leukemia (ALL) with improving patient outcomes. We have recently reported that outcomes of adult patients (pts) with ALL in complete remission (CR) receiving HaploSCT are comparable to unrelated donor transplants. We now compared HaploSCT and matched sibling donor (MSD) transplants in pts with ALL. Aim: To assess transplantation outcomes of HaploSCT and MSD transplants in pts with ALL in CR. Methods: We retrospectively analyzed adult patients (≥ 18 years) with ALL who underwent their first allogeneic stem cell transplantation (alloSCT) in first or second CR between 2012 and 2018, either from a T cell replete Haplo or MSD donor, and whose data were reported to the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional hazards regression model. Propensity score matching was also performed to reduce confounding effects. Results: The analysis comprised 2304 patients: HaploSCT-413; MSD-1891. Median follow-up was 25 months. Median age was 37 (range 18–75) and 38 (18–76) years in HaploSCT and MSD, respectively. HaploSCT patients were transplanted more recently than those transplanted from MSD (2016 vs 2015, p < 0.0001). A higher rate of HaploSCT was in CR2 (33.4% vs 16.7%, p < 0.0001), respectively, and fewer received myeloablative conditioning (68% vs 83.2%, p < 0.0001). Cytomegalovirus (CMV) seropositivity was lower in HaploSCT patients (22% vs 28%, p = 0.01) and donors (27.1% vs 33%, p < 0.02), and a higher proportion of the HaploSCTs were performed using a bone marrow (BM) graft (46.2% vs 18.6%, p < 0.0001). The 2 groups did not differ with regard to gender, Karnofsky performance status score, ALL phenotype, Philadelphia chromosome (Ph) positivity and pre-alloSCT measurable residual disease (MRD). Graft versus host disease (GVHD) prophylaxis was mainly post-transplant cyclophosphamide (PTCy) based (92.7%) in the HaploSCT setting, while it was mostly pharmacologic in the setting of MSD (18.7% received ATG). Cumulative incidence of engraftment at day 60 was higher in MSD transplants compared to HaploSCT (98.7% vs 96.3%, p = 0.001), respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was higher in HaploSCT vs. MSD: 36.3% vs 28.9% (p = 0.002 and 15.2% vs 10.5% (p = 0.005), respectively. Conversely, the 2-year chronic (c) GVHD and extensive cGVHD were 32% vs 38.8% (p = 0.009) and 11.9% vs 19.5% (p = 0.001) in HaploSCT vs MSD, respectively. Main causes of death were leukemia (31.8% vs 45%), infection (33.1% vs 19.7%) and GVHD (16.6% vs 19.7%) for HaploSCT and MSD, respectively. Two-year relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 26% vs 31.6%, 22.9% vs 13%, 51% vs 55.4%, 58.8% vs 67.4% and 40.6% vs 39% for HaploSCT and MSD, respectively. In the MVA, RI was significantly lower in HaploSCT in comparison with MSD, hazard ratio (HR) = 0.66 (95% CI 0.52–0.83, p = 0.004), while NRM was significantly higher, HR = 1.9 (95% CI 1.43–2.53, p < 0.0001). aGVHD grade II-IV and grade III-IV were higher in HaploSCT than in MSD HR = 1.53 (95% CI 1.23–1.9, p = 0.0002) and HR = 1.54 (95% CI 1.1–2.15, p = 0.011), respectively. Extensive cGVHD was lower in HaploSCT compared with MSD, HR = 0.61 (95% CI 0.43–0.88, p = 0.007), while total cGVHD did not differ significantly, HR = 0.94 (95% CI 0.74–1.18, p = 0.58). LFS, OS and GRFS did not differ significantly between the 2 transplant groups, HR = 0.96 (95% CI 0.81–1.14, p = 0.66); HR = 1.18 (95% CI 0.96–1.43, p = 0.11) and HR = 0.93 (95% CI 0.79–1.09, p = 0.37), respectively. These results were confirmed in a matched-pair analysis. Conclusions: Outcomes of adult patients with ALL in CR receiving alloSCT from haploidentical donors are not significantly different from those receiving transplants from MSD in terms of LFS, OS and GRFS. [ABSTRACT FROM AUTHOR]