The Effect of Donor Type on Outcomes in Adults with Acute Myeloid Leukemia after Reduced Intensity Hematopoietic Peripheral Blood Cell Transplant
Transplant international : official journal of the European Society for Organ Transplantation. 2020
We retrospectively analyzed outcomes in patients with acute myeloid leukemia (AML) receiving reduced intensity conditioning (RIC) hematopoietic stem cell transplants (HCT) from a peripheral blood (PB) source. We identified 46 haploidentical HCT (haplo), 59 matched unrelated donor HCT (MUD), and 40 matched related donor HCT (SIB) patients at a single institution. Haplo had improved overall survival (OS) when compared to MUD, HR 2.03 (p=0.01) but not SIB, HR 1.17, (p=0.61). There were no differences in relapse rates or treatment related mortality (TRM). Haplo had higher rates of acute graft versus host disease (GVHD) grade II-IV at day 180 than MUD (44% vs 25%, p=0.03) and SIB (44% vs 13% p<0.01). Rates of acute GVHD III-IV and chronic GVHD were similar among the groups. Haplo had slower engraftment rates compared to MUD with neutrophil engraftment at 87% vs 93%, (p<0.01) and platelet engraftment at 59% vs 86%, (p<0.01) at 28 days. Although patients receiving haplo had higher acute GVHD II-IV and slower engraftment, they did not have increased TRM. These data may suggest that patients receiving haplo have improved OS compared to MUD for AML patients receiving RIC transplants. This should be confirmed using a larger cohort.
The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) Score for HLA Class I Graft-Versus-Host Disparity Is Associated with Increased Acute Graft-Versus-Host Disease in Haploidentical Transplantation with Post-Transplant Cyclophosphamide
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score quantifies the number of PIRCHE between patient and donor pairs and represents an in silico measure of indirect alloreactivity. This biologic process is defined as T cell recognition of epitopes derived from mismatched, allogeneic HLA peptides that are subsequently presented by shared HLA molecules. Its association with clinical outcome has not been examined in haplo-HCT with PTCy. We hypothesized that PIRCHE scores would correlate with indirect alloreactivity and predict graft-versus-host disease (GvHD) risk and incidence of relapse after haplo-HCT with PTCy. To address this, we retrospectively analyzed 148 patients who received peripheral blood, T cell-replete haplo-HCT with PTCy at a single center between 2009 and 2016. PIRCHE scores (PS) were calculated using the PIRCHE online matching tool. PS were categorized by class and vector. The median class I graft-versus-host (GvH) PS was 11 (range, 0-56), while the median class I host-versus-graft (HvG) PS was 10 (range 0-51). The class I GvH PS was associated with increased grade II-IV aGvHD (adjusted HR or aHR 1.03 per PS unit increase; 95% CI 1.01-1.05; p=0.008) but not chronic GvHD or incidence of relapse. PIRCHE scores represent a novel strategy to predict clinical outcome in haplo-HCT. Further studies using registry data and prospective cohorts are warranted to validate these findings.
Cutaneous Graft Versus Host Disease Outcomes are Similar in Haploidentical and Matched Unrelated Hematopoietic Transplant Recipients: A Retrospective Cohort Study
Journal of the American Academy of Dermatology. 2019
BACKGROUND Cutaneous GVHD is common post hematopoietic cell transplant. Haploidentical transplants (Haplo) have historically higher rates of GVHD with overall outcomes improved with the use of post-transplant cyclophosphamide. Specific cutaneous outcomes have not been explored in haploidentical versus matched unrelated donor transplants (MUD). OBJECTIVE To examine the incidence of GVHD in matched unrelated donor (MUD) and haploidentical (Haplo) transplants. METHODS Retrospective cohort study of patients' records that received MUD or Haplo transplants from 2010 - 2015 with determination of GVHD severity and features by one investigator. RESULTS The Haplo cohort included more minorities (22.7% vs. 6.8%; p < 0.001). Incidence of acute cutaneous GVHD was similar (Haplo 47.7% CI: 37.0-58.6 vs. MUD 42.6% CI: 37.9-47.3%; p=0.41). Chronic GVHD was also similar (Haplo 17.1%, CI 9.9-26.6 vs. MUD 12.8% CI: 9.9-16.3; p=0.31). The Haplo group had lower rates of sclerosis (13.3%, CI 1.7-4.05 vs. 50.9%, CI 37.3-64.4; p=0.0095). Other secondary outcomes showed no difference. LIMITATIONS Severity of GVHD was determined retrospectively and not all patients were seenby a dermatologist. CONCLUSIONS No difference was observed between rates or severity of acute or chronic GVHD. Sclerosis was less common in the Haplo group.
HLA epitope mismatch in haploidentical transplantation is associated with decreased relapse and delayed engraftment
Blood advances. 2018;2(24):3590-3601
HLA disparity is traditionally measured at the antigen or allele level, and its impact on haploidentical hematopoietic cell transplantation (haplo-HCT) with high-dose posttransplant cyclophosphamide (PTCy) is unclear. To the best of our knowledge, the relationship between HLA eplet-derived epitope mismatch (EM) and clinical outcome has not been examined in haplo-HCT. We retrospectively analyzed 148 patients who received a peripheral blood, T-cell-replete haplo-HCT with PTCy at a single center. HLA EM was quantified using an HLAMatchmaker-based method and was stratified by class and vector. The primary outcome was incidence of relapse. The total number of mismatched epitopes (MEs) per patient-donor pair in our patient population ranged from 0 to 51 (median, 24) in the graft-versus-host (GVH) direction and 0 to 47 (median, 24) in the host-versus-graft (HVG) direction. Higher HLA class II EM in the GVH direction was associated with a significantly reduced risk of relapse (adjusted hazard ratio [HR], 0.952 per ME; P = .002) and improved relapse-free survival (adjusted HR, 0.974 per ME; P = .020). Higher HLA class II EM in the HVG direction was associated with longer time to neutrophil (adjusted HR, 0.974 per ME; P = .013) and platelet (adjusted HR, 0.961 per ME; P = .001) engraftment. In peripheral blood haplo-HCT patients, increased HLA EM was associated with a protective effect on the risk of relapse in the GVH direction but a negative effect on time to count recovery in the HVG direction. HLA EM based on the HLA Matchmaker represents a novel strategy to predict clinical outcome in haplo-HCT.
Population 148 patients who received a peripheral blood, T-cell-replete haplo-HCT with high-dose posttransplant cyclophosphamide
Intervention Measurement of epitope mismatch
Outcome Higher HLA class II EM in the GVH direction was associated with a significantly reduced risk of relapse and improved relapse-free survival. Higher HLA class II EM in the HVG direction was associated with longer time to neutrophil and platelet engraftment. In peripheral blood haplo-HCT patients, increased HLA EM was associated with a protective effect on the risk of relapse in the GVH direction but a negative effect on time to count recovery in the HVG direction
Propensity Score Analysis of Conditioning Intensity in Peripheral Blood Haploidentical Hematopoietic Cell Transplantation
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
T-cell replete HLA-haploidentical hematopoietic cell transplantation (haplo HCT) with post-transplant cyclophosphamide was originally described using a reduced-intensity conditioning (RIC) regimen. Given that myeloablative conditioning (MAC) is more effective at preventing disease relapse, we compared outcomes of patients receiving MAC and RIC regimens. We evaluated overall survival (OS), disease free survival (DFS), relapse, non-relapse mortality (NRM), and graft versus host disease (GvHD) of 148 patients that underwent haplo HCT with either MAC (n = 61) or RIC (n = 87). Propensity score adjustment (PSA) was used to balance baseline characteristics between groups and more effectively compare outcomes based on conditioning intensity. After the PSA analysis, relapse was significantly decreased with MAC (HR 0.47, 95% CI 0.31-0.70), but was associated with higher NRM (HR 1.74, 1.13-2.67). OS and DFS were not significantly different between groups (HRs for MAC vs. RIC were 0.87, 95% CI 0.64-1.18 and 0.90, 95% CI 0.68-1.18, for OS and DFS, respectively). Rates of acute and chronic GvHD were not significantly different between groups. This analysis suggests that both MAC and RIC regimens are effective in haplo HCT and that MAC regimens may result in less relapse in selected patients. These results need to be verified in a larger registry study.
The impact of diabetes mellitus and other comorbidities on hematopoietic stem cell collection and hematologic recovery post-transplantation
Leukemia & Lymphoma. 2017;58(1):241-243
Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for High-Risk Acute Lymphoblastic Leukemia
Biology of Blood & Marrow Transplantation. 2017;23(2):318-324
Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months. Thirty-two patients were in first complete remission (CR1), while the rest were beyond CR1. Neutrophil engraftment occurred in 95% of the patients. The cumulative incidences of grades II to IV and III and IV acute GVHD at day 100 after transplantation were 32% and 11%, respectively, whereas chronic GVHD, nonrelapse mortality, relapse rate, and disease-free survival (DFS) at 1 year after transplantation were 32%, 21%, 27%, and 51%, respectively. Patients in CR1 had 52% DFS at 3 years. These results suggest that haploidentical transplants performed with PTCy-based GVHD prophylaxis provide a very suitable alternative to HLA-matched transplantations for patients with ALL.
Epidemiology of infections following haploidentical peripheral blood hematopoietic cell transplantation
Transplant Infectious Disease. 2017;19(1)
BACKGROUND The use of T-cell replete haploidentical hematopoietic cell transplant (haplo-HCT) has increased substantially since the introduction of post-transplant cyclophosphamide (PTCy) regimens. Limited data exist concerning infectious complications of haplo-HCT utilizing mobilized peripheral blood (PB) hematopoietic cells. METHODS This retrospective cohort study included all adult patients at our institution undergoing PB haplo-HCT with PTCy between June 2009 and June 2015. Infections were microbiologically confirmed. Invasive fungal infections (IFI) classified as "proven" or "probable" by standard definitions were included. RESULTS In total, 104 patients were identified. Median follow-up was 218 days (range: 6-1576). A total of 322 episodes of infection were recorded. Eighty-nine percent of patients experienced at least one infection. Median time to first infection was 22 days. Patients experiencing at least one bacterial, viral, and IFI were 62%, 72%, and 6%, respectively. The majority (69%) of bacterial infections were caused by enteric organisms. Seven cases of Staphylococcus aureus infection were recorded, with one bacteremia case. Cytomegalovirus (CMV) viremia occurred in 54/71 (76%) at-risk patients at a median time of 24 days. Sixteen (15%) patients developed CMV disease. Nineteen percent (20/104) of patients developed BK polyomavirus-associated cystitis. Six (6%) patients experienced a total of seven IFI. Infection was the primary cause of death for 12% (6/51) of patients and was a secondary cause for 41%. CONCLUSION In PB haplo-HCT patients, a high incidence of CMV viremia and disease was observed. Infections with enteric bacteria were common. Fungal and staphylococcal infections were uncommon. Further studies are needed to compare infectious complications in haplo-HCT with other transplant modalities.
Untreated donor specific antibodies against HLA are associated with poor outcomes in peripheral blood haploidentical hematopoietic cell transplantation
Bone Marrow Transplantation. 2017;52(6):898-901
T Cell-Replete Peripheral Blood Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide Results in Outcomes Similar to Transplantation from Traditionally Matched Donors in Active Disease Acute Myeloid Leukemia
Biology of Blood & Marrow Transplantation. 2017;23(4):648-653
Outcomes for patients with acute myeloid leukemia (AML) who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there are little data comparing outcomes for AML patients with active disease who receive haploidentical versus traditionally matched HCT. We retrospectively analyzed data from 99 AML patients with active disease undergoing allogeneic HCT at a single institution. Forty-three patients received unrelated donor HCT, 32 patients received matched related donor HCT, and 24 patients received peripheral blood haploidentical HCT with post-transplantation cyclophosphamide. We found no significant differences between treatment groups in terms of overall survival (OS), event-free survival, transplantation-related mortality, cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GVHD). We performed univariate regression analysis of variables that modified OS in all patients and found only younger age at transplantation and development of chronic GVHD significantly improved outcome. Although limited by our relatively small sample size, these results indicate that haploidentical HCT in active AML patients have comparable outcomes to HCT with traditionally matched donors. Haploidentical HCT can be considered in this population of high-risk patients when matched donors are unavailable or when wait times for transplantation are unacceptably long.