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1.
Graft-versus-host disease after an outpatient peripheral blood hematopoietic cell transplant using reduced-intensity conditioning: a single-center LATAM experience
Jaime-Pérez, J. C., Meléndez-Flores, J. D., Valdespino-Valdes, J., Gómez-De León, A., Colunga-Pedraza, P. R., Gutiérrez-Aguirre, C. H., Cantú-Rodríguez, O. G., Gómez-Almaguer, D.
Expert review of hematology. 2024;:1-10
Abstract
BACKGROUND HLA compatibility predicts allogeneic hematopoietic cell transplant (allo-HCT) and graft-versus-host disease (GvHD) outcomes. There is insufficient information regarding GvHD outcomes for outpatient HLA-identical and haploidentical-HCT employing reduced-intensity conditioning (RIC). RESEARCH DESIGN AND METHODS We compare GvHD outcomes between donor types and report risk factors associated with GvHD. Stem cell source was T-cell replete peripheral blood. GvHD prophylaxis was post-transplant cyclophosphamide (PT-CY), mycophenolic acid, and calcineurin inhibitors for haploidentical (n = 107) and oral cyclosporine (CsA) plus methotrexate i.v. for HLA-identical (n = 89) recipients. RESULTS One hundred and ninety-six HCT transplant patients were included. aGvHD and cGvHD frequency were similar between HCT types. aGvHD severity was comparable, but severe cGvHD was less frequent in the haploidentical group (p = .011). One-hundred-day cumulative incidence (CI) of aGvHD for haploidentical and HLA-identical was 31% and 33% (p = .84); 2-year CI of cGvHD was 32% and 38% (p = .6), respectively. Haploidentical recipients had less steroid-refractory cGvHD (p = .043). Patients with cGvHD had less 2-year relapse (p = .003); both aGvHD and cGvHD conferred higher OS (p = .010 and p = .001), respectively. Male sex was protective for steroid-refractory cGvHD (p = .028). CONCLUSIONS Acute and chronic GvHD rates were comparable between HLA-identical and haploidentical transplant groups. cGvHD severity was lower in the haploidentical group.
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2.
Impact of chronic graft-versus-host disease on quality of life and cognitive function of long-term transplant survivors after allogeneic hematopoietic stem cell transplantation with total body irradiation
Gruber, I., Koelbl, O., Herr, W., Holler, E., Edinger, M., Wolff, D.
Radiation oncology (London, England). 2022;17(1):195
Abstract
BACKGROUND Total body irradiation (TBI)-based-conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) is standard of care in patients with acute myeloid leukemia (AML) but can cause long-term morbidity. Data on the impact of chronic Graft-versus-host disease (cGvHD) on cognitive function (CF) and quality of life (QoL) of long-term transplant survivors are sparse. METHODS We analyzed patient-reported outcomes focusing on progression-free AML patients and 1st allo-HSCT applying a standardized TBI-technique with an average dose rate of 4 cGy/min to the total body and lung shielding in case of doses > 8 Gy. Instruments included the Functional Assessment of Cancer Therapy-Bone marrow transplant (FACT-BMT, version 4), the FACT-Cognition Function (FACT-Cog, version 3) and the Patient Health Questionaire-4 (PHQ-4). We put focus on the impact of cGvHD and compared the results to normative data derived from the general population. RESULTS Out of 41 eligible patients contacted, 32 (78.0%) patients with a medium follow-up of 154 months (Interquartile range 113, 191 months) participated in the study. Eleven patients (34.4%) had active cGvHD, 11 (34.4%) resolved cGvHD and 10 (31.3%) never had cGvHD. Patients with active cGvHD had poorer FACT-BMT, FACT-Cog and higher PHQ-4 scores compared to patients with resolved cGvHD or who never had cGvHD. Outcomes were similar in patients with resolved cGvHD and those who never had cGvHD. Patients with active cGvHD had similar FACT-Cog, but lower FACT-BMT in comparison to normative data. However, the overall patient sample had similar FACT-BMT and FACT-Cog in comparison to normative data. CONCLUSION Our data indicate that CF of long-term survivors upon TBI-based allo-HSCT is not impaired, even in the presence of active cGvHD. However, active cGvHD has a negative impact on QoL. Trial registration The local Ethics Board of the University of Regensburg approved this study (Number 20-1810_1-101).
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3.
Prediction of the risk for graft versus host disease after allogeneic hematopoietic stem cell transplantation in patients treated with mogamulizumab
Kamada, Y., Arima, N., Hayashida, M., Nakamura, D., Yoshimitsu, M., Ishitsuka, K.
Leukemia & lymphoma. 2022;:1-7
Abstract
Mogamulizumab (Mog), an anti-C-C motif chemokine receptor 4 (CCR4) antibody, is a therapeutic for adult T-cell leukemia/lymphoma (ATL). Injuries of normal regulatory T cells (Tregs) which express CCR4 by Mog could result in immune-related adverse events including graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we retrospectively analyzed 25 patients among 39 patients with ATL who received allo-HSCT. We found that the risk of grade II to IV GVHD was higher in patients who received Mog before or after allo-HSCT (Mog+) than in those who did not (Mog-). The incidence of severe intestinal GVHD and cytomegalovirus (CMV) enteritis were significantly higher in Mog + patients and resulted in death from GVHD or CMV enteritis. Treg numbers were suppressed until Mog serum concentrations became undetectable. Measuring the concentration of Mog and/or the number of Tregs at the time of allo-HSCT might predict the risk of GVHD.
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4.
Mitigation of gastrointestinal graft versus host disease with tocilizumab prophylaxis is accompanied by preservation of microbial diversity and attenuation of enterococcal domination
Chhabra, S., Szabo, A., Clurman, A., McShane, K., Waters, N., Eastwood, D., Samanas, L., Fei, T., Armijo, G., Abedin, S., et al
Haematologica. 2022
Abstract
Not available.
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5.
Drugs as a Frequent Cause of Acute Rash in Patients After CD34(+)-selected Peripheral Blood Stem Cell Transplantation
Klager, S., Lacouture, M. E., Hannum, M., Devlin, S. M., Maloy, M., Pulitzer, M., Jakubowski, A. A., Markova, A.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
While histopathologic differences have been reported between acute graft-versus-host disease (aGVHD) and non-aGVHD rash in CD34(+)-selected peripheral blood stem cell transplantation (PBSCT) recipients, skin biopsies alone are usually insufficient to determine rash etiology. As such, distinguishing inflammatory non-aGVHD rashes, such as drug eruptions, from cutaneous aGVHD after CD34(+)-selected PBSCT remains challenging and relies on clinical presentation. This study aimed to identify etiologies of skin rash in the first year after CD34(+)-selected PBSCT and to assess whether laboratory serologic markers, transplant characteristics, and rash morphology and symptomatology aid in differentiation of cutaneous aGVHD versus non-aGVHD rash. We conducted a retrospective study of 243 adult patients who received a CD34(+)-selected PBSCT at Memorial Sloan Kettering Cancer Center between 2008 and 2011. Among this cohort of transplant recipients, only 43 patients (17.7%) developed cutaneous aGVHD. In total, 152 patients (63%) were identified with rash within one year after PBSCT. The proportion of patients who experienced peripheral eosinophilia was not different between those with an aGVHD versus non-aGVHD rash (p ≥0.9), nor when stratified by CD34(+) selection method (Isolex p=0.7; CliniMACS p ≥0.9). The proportion of patients with pruritus was also not different between those with an aGVHD versus non-aGVHD rash (p=0.20), nor when stratified by CD34(+) selection modality (Isolex p=0.2; CliniMACS p=0.5). The most common cause of non-aGVHD rash among those with a clear etiology was drug (39% of Isolex; 26% of CliniMACS). Single drug culprits were identified in 51% of drug rashes. The most commonly reported offending agents included antibiotics, keratinocyte growth factor (KGF), chemotherapy, and recombinant glycosylated human interleukin-7 (IL-7).
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6.
Reduced intensity conditioning increases risk of severe cGVHD: identification of risk factors for cGVHD in a multicenter setting
Afram, G., Simon, J. A. P., Remberger, M., Caballero-Velazquez, T., Martino, R., Pinana, J. L., Ringden, O., Esquirol, A., Lopez-Corral, L., Garcia, I., et al
Medical oncology (Northwood, London, England). 2018;35(6):79
Abstract
Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.
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7.
Risk of graft-versus-host disease with rituximab-containing conditioning regimens in allogeneic hematopoietic stem cell transplant
Marini, B. L., Markstrom, D., Frame, D.
Journal of Oncology Pharmacy Practice. , 2016 Mar 11. 2016
Abstract
Graft-versus-host disease represents a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant patients. There is growing evidence that B lymphocytes may play a role in the pathogenesis of acute graft-versus-host disease. The purpose of this retrospective cohort study was to evaluate the efficacy of rituximab-containing conditioning regimens in decreasing graft-versus-host disease in allogeneic hematopoietic stem cell transplant patients who received standardized tacrolimus-based graft-versus-host disease prophylaxis regimens. Patients were divided into two cohorts, based on the presence (RTX, n=54) or absence (No-RTX, n=105) of rituximab in the conditioning regimen and were matched 1:2 for major graft-versus-host disease risk factors. The incidence of grade II-IV acute graft-versus-host disease was not different between the two groups (37% vs. 26%, p=0.147). When restricting the analysis to recipients of peripheral blood hematopoietic stem cell transplants, the RTX group had a higher incidence of grade II-IV acute graft-versus-host disease, relapse, or death prior to day 100 (55% vs. 36%, p=0.037). The median time to the onset of acute graft-versus-host disease was no different between the RTX and No-RTX groups (67 vs. 74 days, respectively, p=0.141). Inhibition of antigen presentation by B cells with rituximab-based conditioning regimens does not appear to reduce the incidence of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplant recipients. Copyright © The Author(s) 2016.
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8.
Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT
Marsh, R. A., Lane, A., Mehta, P. A., Neumeier, L., Jodele, S., Davies, S. M., Filipovich, A. H.
Blood. 2016;127(4):503-12
Abstract
Reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) with alemtuzumab, fludarabine, and melphalan is an effective approach for patients with nonmalignant disorders. Mixed chimerism and graft-versus-host-disease (GVHD) remain limitations on success. We hypothesized that higher levels of alemtuzumab at day 0 would result in a low risk of acute GVHD, a higher risk of mixed chimerism, and delayed early lymphocyte recovery and that alemtuzumab level thresholds for increased risks of these outcomes would be definable. We collected data from 105 patients to examine the influence of peritransplant alemtuzumab levels on acute GVHD, mixed chimerism, and lymphocyte recovery. The cumulative incidences of initial grades I-IV, II-IV, and III-IV acute GVHD in patients with alemtuzumab levels <0.15 vs >0.16 mug/mL were 68% vs 18% (P < .0001), 47% vs 13% (P = .0002), and 32% vs 8%, respectively (P = .005). The cumulative incidence of mixed chimerism in patients with an alemtuzumab level <0.15 mug/mL was 21%, vs 42% with levels of 0.16 to 4.35 mug/mL, and 100% with levels >4.35 mug/mL (P = .003). Patients with alemtuzumab levels <0.15 or 0.16 to 0.56 mug/mL had higher lymphocyte counts at day +30 and higher T-cell counts at day +100 compared with patients with levels >0.57 mug/mL (all P < .05). We conclude that peritransplant alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following RIC HCT with alemtuzumab, fludarabine, and melphalan. Precision dosing trials are warranted. We recommend a day 0 therapeutic range of 0.2 to 0.4 mug/mL. Copyright © 2016 by The American Society of Hematology.