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At-Home Foscarnet Administration in Patients with Cytomegalovirus Infection Post-Allogeneic Stem Cell Transplantation: A Unicentric, Safe, and Feasible Program
Ruiz-Boy, S., Pedraza, A., Prat, M., Salas, M. Q., Carcelero, E., Riu-Viladoms, G., Suárez-Lledó, M., Monge-Escartín, I., Rodríguez-Lobato, L. G., Martínez-Roca, A., et al
Pharmaceuticals (Basel, Switzerland). 2023;16(12)
Abstract
Cytomegalovirus (CMV) infection is a relevant cause of morbimortality in patients receiving allogeneic stem cell transplantation (allo-HCT). Foscarnet (FCN) is an effective drug against CMV administered intravenously and usually on an inpatient basis. The Home Care Unit (HCU) for hematologic patients at our hospital designed an at-home FCN administration model to avoid the hospitalization of patients requiring FCN treatment. This study analyzes whether the at-home administration of FCN is as safe and effective as its hospital administration. We collected and compared demographic, clinical, analytical, and economic data of patients with CMV infection post-allo-HCT who received FCN in the hospital (n = 16, 17 episodes) vs. at-home (n = 67, 88 episodes). The proportions of patients with cured CMV infections were comparable between the two groups (65.9% vs. 76.5%, p = 0.395). The median duration of FCN treatment was 15 (interquartile range [IQR] 9-23) and 14 (IQR 11-19) days in the HCU and inpatient cohorts, respectively (p = 0.692). There were no significant differences in the FCN toxicities between groups except for hypocalcemia (26.1% vs. 58.8%, p = 0.007), which was more prevalent in the inpatient cohort. A significant cost-effectiveness was found in the HCU cohort, with a median savings per episode of EUR 5270. It may be concluded that home administration of FCN is a safe, effective, and cost-efficient therapeutic option for patients with CMV infection and disease.
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Prediction of Nonrelapse Mortality in Patients With Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia Receiving Allogeneic Stem Cell Transplantation With Posttransplantation Cyclophosphamide-based Graft Versus Host Disease Prophylaxis
Hermans, S. J. F., Versluis, J., Labopin, M., Giebel, S., van Norden, Y., Moiseev, I., Blaise, D., Díez Martín, J. L., Meijer, E., Rovira, M., et al
HemaSphere. 2023;7(3):e846
Abstract
Graft versus host disease (GVHD) prophylaxis with posttransplantation cyclophosphamide (PTCY) has been established to reduce severe GVHD, and thereby potentially reducing nonrelapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). We evaluated the predictive capacity of established NRM-risk scores in patients receiving PTCY-based GVHD prophylaxis, and subsequently developed and validated a novel PTCY-specific NRM-risk model. Adult patients (n = 1861) with AML or ALL in first complete remission who received alloSCT with PTCY-based GVHD prophylaxis were included. The PTCY-risk score was developed using multivariable Fine and Gray regression, selecting parameters from the hematopoietic cell transplantation-comorbidity index (HCT-CI) and European Group for Blood and Marrow Transplantation (EBMT) score with a subdistribution hazard ratio (SHR) of ≥1.2 for 2-year NRM in the training set (70% split), which was validated in the test set (30%). The performance of the EBMT score, HCT-CI, and integrated EBMT score was relatively poor for discriminating 2-year NRM (c-statistic 51.7%, 56.6%, and 59.2%, respectively). The PTCY-risk score included 10 variables which were collapsed in 3 risk groups estimating 2-year NRM of 11% ± 2%, 19% ± 2%, and 36% ± 3% (training set, c-statistic 64%), and 11% ± 2%, 18% ± 3%, and 31% ± 5% (test set, c-statistic 63%), which also translated into different overall survival. Collectively, we developed an NRM-risk score for acute leukemia patients receiving PTCY that better predicted 2-year NRM compared with existing models, which might be applicable to the specific toxicities of high-dose cyclophosphamide.
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Applicability and validation of different prognostic scores in allogeneic hematopoietic cell transplant (HCT) in the post-transplant cyclophosphamide era
Salas, M. Q., Rodríguez-Lobato, L. G., Charry, P., Suárez-Lledó, M., Pedraza, A., Solano, M. T., Arcarons, J., Cid, J., Lozano, M., Rosiñol, L., et al
Hematology, transfusion and cell therapy. 2023
Abstract
We investigated the predictive capacity of six prognostic indices [Karnofsky Performance Status (KPS), Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) and Revised Pre-Transplantation Assessment of Mortality (rPAM) Scores and Endothelial Activation and Stress Index (EASIX)] in 205 adults undergoing post-transplant cyclophosphamide (PTCy)-based allo-HCT. KPS, HCT-CI, DRI and EASIX grouped patients into higher and lower risk strata. KPS and EASIX maintained appropriate discrimination for OS prediction across the first 2 years after allo-HCT [receiver operating characteristic curve (area under the curve (AUC) > 55 %)]. The discriminative capacity of DRI and HCT-CI increased during the post-transplant period, with a peak of prediction at 2 years (AUC of 61.1 % and 61.8 %). The maximum rPAM discriminative capacity was at 1 year (1-year AUC of 58.2 %). The predictive capacity of the EBMT score was not demonstrated. This study validates the discrimination capacity for OS prediction of KPS, HCT-CI, DRI and EASIX in PTCy-based allo-HCT.
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Reduced 8-Gray Compared to Standard 12-Gray Total Body Irradiation for Allogeneic Transplantation in First Remission Acute Lymphoblastic Leukemia: A Study of the Acute Leukemia Working Party of the EBMT
Spyridonidis, A., Labopin, M., Savani, B., Giebel, S., Bug, G., Schönland, S., Kröger, N., Stelljes, M., Schroeder, T., McDonald, A., et al
HemaSphere. 2023;7(1):e812
Abstract
In this registry-based study, we compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in adult patients with acute lymphoblastic leukemia (ALL) transplanted in first complete remission (CR-1), following conditioning with total body irradiation (TBI) at a standard 12-Gray or at a lower 8-Gray total dose. Patients received fludarabine (flu) as the sole chemotherapy complementing TBI. Eight-Gray TBI/flu was used in 494 patients and 12-Gray TBI/flu in 145 patients. Eighty-eight (23.1%) and 36 (29%) of the patients had Ph-negative B-ALL, 222 (58.3%) and 53 (42.7%) had Ph-positive B-ALL, 71 (18.6%) and 35 (28.2%) T-ALL, respectively (P = 0.008). Patients treated with 8-Gray were older than ones received 12-Gray (median 55.7 versus 40.3 years, P < 0.0001) and were more frequently administered in vivo T-cell depletion (71% versus 40%, P <0.0001). In a multivariate model adjusted for age, type of ALL, and other prognostic factors, leukemia-free survival (primary endpoint) as well as relapse, nonrelapse mortality, overall survival, and GVHD-free, relapse-free survival were not influenced by the TBI dose. These results were confirmed when we focused on patients <55 years of age (median 47 years). Patients with Ph-positive ALL or T-ALL had significantly better survival outcomes than ones with Ph-negative B-ALL, mainly due to significantly fewer relapses. We conclude that 8-Gray TBI is sufficient for adult patients with ALL transplanted in CR-1 with no additional benefit of augmenting the conditioning intensity to 12-Gray.
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Monitoring for virus-specific T-cell responses and viremia in allogeneic HSCT recipients: a survey from the EBMT Cellular Therapy & Immunobiology Working Party
Greco, R., Hoogenboom, J. D., Bonneville, E. F., Anagnostopoulos, A., Cuoghi, A., Dalle, J. H., Weissinger, E. M., Lang, P., Galaverna, F., Martino, M., et al
Bone marrow transplantation. 2023;:1-4
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Comparison of outcomes after unrelated double-unit cord blood and haploidentical peripheral blood stem cell transplantation in adults with acute myeloid leukemia, a study on behalf of Eurocord and ALWP-EBMT
Ruggeri, A., Galimard, J. E., Labopin, M., Rafii, H., Blaise, D., Ciceri, F., Diez-Martin, J. L., Cornelissen, J., Chevallier, P., Sanchez-Guijo, F., et al
Transplantation and cellular therapy. 2022
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Editor's Choice
Abstract
BACKGROUND Unmanipulated haploidentical stem cell transplantation with post-transplant cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis (Haplo-PTCY) and unrelated double-unit umbilical cord blood transplant (dUCBT) are feasible options to treat patients with high risk acute myeloid leukemia (AML). OBJECTIVES The aim of our study was to compare outcomes after dUCBT and Haplo-HCT using PBSC in adult patients with AML in complete remission (CR) transplanted in European Society for Blood and Marrow Transplantation (EBMT) affiliated centers. STUDY DESIGN In a population of adults with de novo AML in first or second CR, we compared outcomes after dUCBT (n=165) and after Haplo-PTCY PBSC (n=544) performed between January 2013 and December 2018. Patients receiving in-vivo antithymocyte globuline (ATG), Campath, or ex-vivo T-cell depletion were excluded. RESULTS Median follow-up was 33 months for Haplo-PTCY and 52 months for dUCBT. No statically significant differences were observed between the two approaches in grade-II-IV acute-GVHD (hazard ratio [HR]=1.31, p=0.18), and grade-III-IV (HR=1.17, p=0.56) or in chronic-GVHD (HR=0.86, p=0.48) or relapse (HR=1.07, p=0.77), non-relapse mortality (NRM; HR=0.94, p=0.77), leukemia-free survival (LFS; HR=0.99, p=0.95) and overall survival (OS; HR=0.99, p=0.97) when comparing dUCBT with Haplo-PTCY. Favourable cytogenetic risk was the only factor predictive of lower relapse incidence. Younger age at transplant was associated with lower NRM and higher LFS and OS. CONCLUSION Both dUCBT and Haplo-PTCY with PBSC can be considered as valid approaches for adult AML patients in complete remission. New strategies should be investigated in both settings to define the most appropriate conditioning regimen and potentially, to decrease relapse incidence and NRM through better immune reconstitution and optimal supportive care.
PICO Summary
Population
Adults with acute myeloid leukaemia having first allogeneic transplant, and reported to the EBMT or Eurocord registries (n=709)
Intervention
Double cord blood transplantation (dUCBT, n=165)
Comparison
Haploidentical transplant with post-transplant cyclophosphosphamide (Haplo-PTCY, n=544)
Outcome
No statistically significant differences were observed between the two approaches in grade-II-IV acute-GVHD (hazard ratio [HR]=1.31), and grade-III-IV (HR=1.17) or in chronic-GVHD (HR=0.86) or relapse (HR=1.07), non-relapse mortality (NRM; HR=0.94), leukemia-free survival (LFS; HR=0.99) and overall survival (OS; HR=0.99) when comparing dUCBT with Haplo-PTCY. Favourable cytogenetic risk was the only factor predictive of lower relapse incidence. Younger age at transplant was associated with lower NRM and higher LFS and OS.
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Effect of CD34+ cell dose on the outcomes of allogeneic stem cell transplantation with post-transplant cyclophosphamide
Pedraza, A., Salas, M. Q., Rodríguez-Lobato, L. G., Charry, P., Suárez-Lledo, M., Martínez, N., Doménech, A., Solano, M. T., Arcarons, J., de Llobet, N., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND The impact of infused CD34+ cell dose on the outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) using standard graft-versus-host disease (GVHD) prophylaxis remains controversial. Information on this subject is scarce for alloHSCT using high-dose post-transplant cyclophosphamide (PTCy). OBJECTIVES We aim to assess the effect of CD34+ cell dose in peripheral blood stem cells (PBSC) grafts on the outcome of alloHSCT using PTCy-based GVHD prophylaxis. STUDY DESIGN We conducted a single center retrospective analysis on 221 consecutive adult patients who received PTCy alloHSCT from HLA-matched sibling donors (MSD) (N=22), HLA-matched (MUD) (N=83), mismatched unrelated donors (MMUD) (N=73), and haploidentical donors (N=43). Based on the binary partitioning method, 5 × 10(6)/kg was used as the optimal cut-off of CD34+ cell dose. According to our institutional protocol, the maximum CD34+ cell dose was capped at 8 × 10(6)/kg. The study cohort was separate in two groups: CD34+ cells high-dose (> 5 to 8 × 10(6)/kg) and low-dose (≤ 5 × 10(6)/kg). RESULTS Patients receiving high-dose CD34+ containing grafts had a significantly shorter median time to neutrophil (19 vs. 21 days, P=0.002) and platelet engraftment (16 vs. 22 days, P=0.04) compared to those who received low-dose CD34+. No differences between high-dose and low-dose groups were observed in the cumulative incidence of day +100 acute GVHD (grade II-IV: 25% vs. 23%, P=0.7; and grade III-IV: 5% vs. 4%, respectively, P=0.4), or 2-year chronic GVHD (moderate/severe GVHD 9% vs. 6%, P=0.5). No impact of CD34+ cell dose on survival outcomes when using MSD, MUD or MMUD was observed. Recipients of haploidentical alloHSCT using low-dose CD34+ cell had significant worse overall survival (HR 6.01, P=0.004) and relapse free survival (HR 4.57, P=0.004). CONCLUSIONS In patients receiving PBSC PTCy alloHSCT, infused CD34+ cell doses > 5 to 8 × 10(6)/kg was associated with faster neutrophil and platelet engraftment, independently of the type of donor. Our study suggest an impact of CD34+ cell dose on survival outcomes only with haploidentical donors, for whom the administration of a CD34+ cell dose ≤ 5 × 10(6)/kg significantly decreased survival outcomes.
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Posttransplant cyclophosphamide-based anti-graft-vs-host disease prophylaxis in patients with acute lymphoblastic leukemia treated in complete remission with allogeneic hematopoietic cell transplantation from human leukocyte antigen-mismatched unrelated donors versus haploidentical donors: A study on behalf of the ALWP of the EBMT
Nagler, A., Labopin, M., Arat, M., Reményi, P., Koc, Y., Blaise, D., Angelucci, E., Vydra, J., Kulagin, A., Socié, G., et al
Cancer. 2022
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Editor's Choice
Abstract
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 × 10(9) /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.
PICO Summary
Population
Adults with high-risk acute lymphoblastic leukemia (ALL) in complete remission, lacking a matched donor (n=781)
Intervention
9/10 mismatched unrelated donor transplantation (MMUD, n=103)
Comparison
Haploidentical transplantation (haplo, n=678)
Outcome
Neutrophil (absolute neutrophil count >0.5 × 10(9) /L) recovery was achieved in 97.1% versus 96.7% versus 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) and HR = 0.81 (95% CI, 0.52-1.28), 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), HR = 1.17 (95% CI, 0.77-1.76), and HR = 1.07 (95% CI, 0.78-1.46) 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), whereas aGVHD grade 3-4 and chronic GVHD did not differ significantly between the two transplant groups.
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Bacterial Bloodstream Infections in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide
Salas, M. Q., Charry, P., Alcalde, P. P., Cibrian, N. M., Solano, M. T., Serrahima, A., Nomdedeu, M., Cid, J., Lozano, M., Chumbinta, M., et al
Transplantation and cellular therapy. 2022
Abstract
This study investigates the incidence and predictors for bacterial bloodstream infection (BSI) in 330 adults undergoing allo-HCT, and explores the effect of PTCY on the probability of presenting this complication. All patients received levofloxacin during the aplastic phase. Only the first episode of BSI was accounted as an event. Patients were classified into two groups: PTCY-based (n=200) vs. other prophylaxis (n=130). 124 patients were diagnosed with a first episode of BSI, most of them during the first 30 days (70.2%). Proportions of BSIs caused by Gram-positive bacteria were comparable to those caused by Gram-negative bacteria (48.3% vs. 45.9%). The cumulative incidence of BSI was higher in patients receiving PTCY than in those receiving other prophylaxis (Day +30 and +100: 35.0% and 37.0% vs. 13.1% and 18.5%, P<0.001). At day +30, the likelihood of BSI was 2.41 (P=0.012) times higher in the PTCY's than in the non-PTCY's group. The day 30 mortality rate in all patients with BSI was 8.0%, lower (P=0.002) in the PTCY's group (2.3%) than in the non-PTCY's one (21.6%). Finally, the overall survival of patients receiving PTCY and diagnosed with BSI was similar to that of patients without presenting this complication.
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PTCY and Tacrolimus for GVHD Prevention for Older Adults Undergoing HLA-Matched Sibling and Unrelated Donor AlloHCT
Salas, M. Q., Charry, P., Pedraza, A., Martínez-Cibrian, N., Solano, M. T., Domènech, A., Suárez-Lledó, M., Nomdedeu, M., Cid, J., Lozano, M., et al
Transplantation and cellular therapy. 2022
Abstract
INTRODUCTION The use of PTCY for graft-versus-host disease (GHVD) prevention is becoming prevalent in the transplant community when HLA-identical sibling (MSD) and 10/10 HLA-matched (MUD) and 9/10 mismatched (MMUD) unrelated donors are selected for alloHSCT. However, reported evidence on outcomes from elderly receiving PTCY-containing GVHD prophylaxis remains limited. OBJECTIVES This study aims to compare the outcomes of PTCY-TK prophylaxis and conventional GVHD prophylaxis in patients aged >50 years undergoing peripheral blood alloHSCT from a single institution. STUDY DESIGN A total of 161 consecutive patients aged >50 years undergoing alloHSCT between Jan-2014 and Feb-2021 were included. Data was collected retrospectively and updated in December 2021. Patients received grafts from HLA-identical sibling (MSD), and from 10/10 and 9/10 HLA matched and mismatched unrelated donors (UD). RESULTS Overall, median age was 60 years and 91 (54.8%) received PTCY-TK for GVHD prevention. Time to neutrophil and platelet engraftment was longer in the PTCY-TK group (20 vs. 16 days and 19 vs. 11 days, P< 0.001). The cumulative incidences of grade II-IV and III-IV aGVHD at day +100 and moderate/severe cGVHD at 2 years were 18.2%, 5.7% and 9.5% for patients receiving PTCY-TK, and 26.0%, 9.6% and 39.5% for those that did not. The multivariate analysis showed that PTCY-TK reduced the probability of grade II-IV aGVHD (HR 0.41, p=0.035), of cGVHD [any grade: HR 0.43 (p=0.014), and of moderate/severe cGVHD (HR 0.15 (p<0.001)]. At 2-years, the overall survival (65.4% vs. 65.6%, p=0.472), non-relapse mortality (17.4% vs. 13.7%, p=0.967), and cumulative incidence of relapse rates (24.2% vs. 27.5%, p=0.712) were comparable between both cohorts; GVHD-Free/Relapse-free survival (GRFS) was higher in the PTCY-TK group (2-years: 50.2% vs. 21.8%; HR 0.42, p=0.001). In patients aged ≥50 years, Conclusion: PTCY-TK was safe and a more effective drug combination than non-PTCY containing GVHD prophylaxis, even with the use of matched and mismatched UD, and resulted in comparable relapse rates and better GRFS.