Oral fludarabine is an effective and convenient alternative to intravenous fludarabine in fludarabine melphalan based reduced intensity conditioning regimens

Internal Medicine Journal

Biscoe

et al. 2023

BackgroundCorticosteroids (CSs) have previously been incorporated into graft versus host disease (GVHD) prophylaxis regimens for bone marrow (BM) and haemopoietic stem cell transplant (HSCT).AimsTo assess the impact of prophylactic CS in HSCT using peripheral blood (PB) stem cells.MethodsPatients were identified from three HSCT centres receiving a first PB‐HSCT between January 2011 and December 2015 from a fully human leukocyte antigen (HLA)‐matched sibling or unrelated donor for acute myeloid leukaemia or acute lymphoblastic leukaemia. To enable meaningful comparison, patients were divided into two cohorts.ResultsCohort 1 included only myeloablative‐matched sibling HSCT, where the only variation in GVHD prophylaxis was the addition of CS. In these 48 patients, there were no differences in GVHD, relapse, non‐relapse mortality, overall survival or GVHD‐relapse‐free‐survival (GRFS) at 4 years after transplant. Cohort 2 included the remaining HSCT recipients, where one group received CS‐prophylaxis and the non‐CS group received an antimetabolite, ciclosporin and anti‐T‐lymphocyte globulin. In these 147 patients, those receiving CS‐prophylaxis experienced higher rates of chronic GVHD (71% vs 18.1%, P < 0.001) and lower rates of relapse (14.9% vs 33.9%, P = 0.02). Those receiving CS‐prophylaxis had a lower 4‐year GRFS (15.7% vs 40.3%, P = 0.002).ConclusionsThere does not appear to be a role for adding CS to standard GVHD prophylaxis regimens in PB‐HSCT.

Section: Methodsmentioning

confidence: 99%

“…fludarabine (30 mg/m 2 ) over 5 days. 6 Intravenous melphalan followed on Day À2 at 140 mg/m 2 in patients under 60 years and 120 mg/m 2 in patients 60 years and older. FMB was administered to four doses of i.v.…”

Section: Transplantation Process: Conditioningmentioning

confidence: 99%

Long‐term outcomes of corticosteroid graft versus host disease prophylaxis in peripheral blood allogeneic haemopoietic stem cell transplant: a comparative cohort analysis

Blennerhassett

Internal Medicine Journal

Biscoe

et al. 2023

“…The conditioning protocol was determined according to patient and disease characteristics, and categorized as myeloablative (MAC) or reduced intensity (RIC) as previously defined, with nonmyeloablative regimens included as RIC. 28 The most commonly used regimes consisted of fludarabine/melphalan (FluMel) 29 for RIC and busulfan/cyclophosphamide (BuCy) with therapeutic drug monitoring or cyclophosphamide/total body irradiation (CyTBI) for MAC. Standard GVHD prophylaxis consisted of cyclosporin and methotrexate (5-15 mg/m 2 on days +1, +3, +6 and +11); in addition all URD received either "Ruutu" protocol 30 corticosteroids (prior to 2015) or Thymoglobulin (ATG) 4.5 mg/kg (2015 onwards).…”

Section: Hct Protocolmentioning

confidence: 99%

Cytomegalovirus (CMV) management in allogeneic hematopoietic cell transplantation: Pre‐transplant predictors of survival, reactivation, and spontaneous clearance

Lindsay

Transplant Infectious Dis

Kerridge

et al. 2021

Background: Cytomegalovirus (CMV) reactivation is a frequent complication after allogeneic hematopoietic cell transplant (alloHCT). Method:We analyzed 159 alloHCT recipients with 4409 quantitative CMV viral loads to determine pre-transplant predictors of CMV reactivation, clinically significant CMV infection (cs-CMVi, defined as CMV viral load >1000 IU/mL), CMV disease, kinetics of spontaneous clearance of CMV, and survival using a standardized preemptive therapy approach to identify at-risk groups to target prevention strategies.Results: Cs-CMVi was most common in D−/R+ unrelated donor transplants (URD).Spontaneous CMV clearance occurred in 26% of patients who reached a viral load of 56-137 IU/mL, 6% at 138-250 IU/mL and in one patient >250 IU/mL. Median time between the first CMV reactivation (>56 IU/mL) and a viral load >250 IU/mL was 13 days, whereas the time from the first viral load >250 IU/mL to reach a vial load >1000 IU/mL was 4 days. Cs-CMVi was associated with a significant increase in nonrelapse mortality (NRM) on multivariate analysis. Conclusions:Overall, this study indicates that D−/R+ URD recipients are at high-risk for cs-CMVi-and CMV-related mortality, and are potential candidates for targeted

“…Fludarabine was given for 5 days, either i.v. (25 mg/m 2 ) or oral (40 mg/m 2 ) [32]. Intravenous melphalan on day À2 was dosed at 140 mg/m 2 for patients under 60 and 120 mg/m 2 for those 60 and over.…”

Section: Transplantation Proceduresmentioning

confidence: 99%

Unrelated Donor Transplant Recipients Given Thymoglobuline Have Superior GRFS When Compared to Matched Related Donor Recipients Undergoing Transplantation without ATG

Biology of Blood and Marrow Transplantation

Greenwood

Moore

et al. 2020

Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors (URDs) and mismatched related donors (MMRDs) typically have a higher incidence of acute and chronic graft-versus-host disease (GVHD) compared with matched related donors (MRDs). Anti-T-cell globulins (ATGs) are often used to reduce GVHD in these recipients. We report the outcomes of 211 adult peripheral blood stem cell transplant recipients with myeloid malignancies who received a standardized transplant protocol, in which ATG (Thymoglobuline 4.5 mg/kg) was administered to recipients of URD and MMRD (n = 147) but not MRD (n = 64) transplant. For all patients, incidence of acute GVHD grades 2 to 4 was 21.4%, and chronic GVHD was 35.0%. Two-year overall survival was 63.2% (95% confidence interval, 55.8% to 71.5%), relapse-free survival was 55.3% (47.4% to 64.6%), and GVHD-free, relapsefree survival (GRFS) was 30.7% (23.2% to 40.8%). There were no differences between recipients of MRDs and other donors in relapse, nonrelapse mortality, and overall and relapse-free survival. However, compared with MRD, recipients from URDs and MMRDs had reduced moderate to severe chronic GVHD (10.4% versus 30.1%, P= .002), less chronic GVHD requiring systemic therapy (19.4% versus 38.9%, P = .006), and superior 2-year GRFS (35.5% versus 20.0%, P = .003). In this retrospective review of nonrandomized transplant groups, outcomes of HSCT performed using an URD with ATG during conditioning were superior to transplant from an MRD without ATG. The addition of Thymoglobuline to conditioning in HSCT from MRD should be further examined in prospective trials.