A single-center retrospective study was conducted at the University of KS Medical Center, examining all adult haplo-HSCT recipients from August 2016 to July 2021. The study included 176 patients with at least one year of post-transplantation follow-up. The cohort consisted of adult patients who received their first allo-HSCT from donors mismatched at two or more HLA loci, independent of conditioning regimen and indication for allo-HSCT. Patients who received manipulated grafts (ex vivo or in vivo T-cell depletion, or ex vivo engineered T cells) were excluded as were those with matched unrelated, mismatched unrelated, matched related, or umbilical cord blood donors. All recipients of haplo-HSCT were administered standard GvHD prophylaxis consisting of PT-Cy, mycophenolate mofetil (MMF), and tacrolimus (continuing until Day +60 after the transplant). The myeloablative and reduced-intensity conditioning (RIC) regimens utilized are listed in Table 1. The institutional review board approved the study.

Data were collected by review of the electronic medical records. Demographic, clinical, and pathologic factors were ascertained at the time of HSCT. The primary objective of this study was to compare overall survival (OS) between the groups. The secondary objectives were to compare rates of acute and chronic GvHD, cytokine release syndrome (CRS), neutrophil and platelet engraftment, non-relapse mortality (NRM), relapse, and disease-free survival (DFS). Neutrophil recovery was defined as achieving an absolute neutrophil count (ANC) >0.5 × 109/L for three consecutive days. Platelet recovery was defined as achieving a platelet count >20 × 109/L without transfusion requirement for seven consecutive days. Disease relapse, progression, and death were treated as events. NRM was defined as time to death without relapse or progression. Relapse was defined as the molecular, cytogenetic, or hematologic recurrence of the primary disorder. DFS was defined as survival without relapse or progression. Acute GvHD (aGvHD) was staged and graded according to the Mount Sinai aGvHD International Consortium criteria [13]. CRS was graded based on American Society for Transplantation and Cellular Therapy Consensus Guidelines [14]. Chronic GvHD (cGvHD) was staged and graded according to the 2014 National Institutes of Health criteria. Causes of death were coded according to the Center for International Blood and Marrow Transplant Research recommendations; specifically, if a patient had an active or uncontrolled GvHD and concurrent infection at the time of death, then GvHD was coded as the primary cause of death and infection was coded as a contributing cause.

Descriptive statistics were used to compare baseline demographic characteristics. Categorical data were compared using the Chi-square test. Continuous data were compared using ANOVA or t-test. Univariate and multivariate Cox regression analyses were conducted to investigate factors associated with OS, DFS, NRM, and relapse including the graft source; the hazard ratio (HR) with 95 % confidence intervals (95 % CIs) were obtained. For regression models, PBSC recipients were compared with reference to BM graft recipients. Univariate regression analyses included correlation of key variables with the post-transplant outcomes, including age, sex, ethnicity, Karnofsky performance status (KPS), hematopoietic stem cell transplantation-specific comorbidity index (HSCT-CI), hematologic diagnosis, disease status (complete remission versus others), recipient cytomegalovirus (CMV) serostatus, donor CMV serostatus, donor age, donor sex, conditioning regimen, and GvHD prophylaxis. Significant factors identified in univariate analyses were entered into a multivariate analysis for the respective outcome. Data were analyzed using SPSS version 28 with statistical significance being defined as a p-value >0.05.

The study encompassed 176 haplo-HSCT involving 114 (65 %) PBSC and 62 (35 %) BM grafts. The median age of recipients was 54 years (range: 18–74); 119 (68 %) were male. The racial distribution was primarily Caucasian (123; 70 %), followed by Hispanic (23; 13 %), Afro-American (16; 9 %), and other ethnicities (14; 8 %). The most common hematologic diagnoses were acute myeloid leukemia (AML) in 74 patients (42 %), other myeloid disorders in 41 (23 %), acute lymphoid leukemia (ALL) in 17 (10 %), lymphoma in 33 (19 %), and other conditions in 11 (6 %). A pre-transplant HSCT-CI score of 3 or higher was recorded in 93 patients (53 %). KPS was ≥90 % in 59 (34 %) and 60–80 % in 117 (67 %) patients. RIC was administered to 121 recipients (69 %) and myeloablative conditioning (MAC) to 55 (31 %). CMV seropositivity was identified in 109 recipients (62 %) and 101 donors (57 %). At the time of transplantation, 111 recipients (63 %) were in complete remission. The median CD34+ cell dose was 5.0 × 106 per kg for PBSC recipients and 2.8 × 106 per kg for BM recipients (p-value <0.001). These data are summarized in Table 2.

With a median follow-up of 21 months (range: 0–73 months), OS and DFS were not reached in either the BM or PBSC haplo-HSCT groups. The one-year OS rates were 75 % for BM and 74 % for PBSC (p-value = 0.898), and the one-year DFS rates were identical at 63 % for both groups (p-value = 0.994). PBSC recipients experienced earlier neutrophil engraftment at 17 days compared to 18 days for BM recipients (p-value = 0.022).

The incidences of Grade II-IV acute GvHD were nearly identical at 50 % for BM and 51 % for PBSC (p-value = 0.875). Relapse rates were 22 % for PBSC and 26 % for BM (p-value = 0.579), while NRM rates were 17 % for PBSC and 20 % for BM (p-value = 0.682). The median times to platelet engraftment were 28 days for PBSC and 31 days for BM (p-value = 0.092). Neutrophil recovery by Day +28 was 95 % for PBSC versus 90 % for BM (p-value = 0.349), and platelet recovery by Day +100 was 90 % for PBSC compared to 81 % for BM (p-value = 0.099). Rates of primary graft failure (PGF) and one-year chronic GvHD were also similar, with PGF at 2 % for PBSC versus 5 % for BM (p-value = 0.347) and chronic GvHD at 35 % for PBSC versus 38 % for BM (p-value = 0.410). The one-year GvHD-free relapse-free survival rate (GRFS) was 67 % for PBSC and 61 % for BM (p-value = 1.00). The overall incidence of CRS was 71 %, significantly higher in PBSC at 90 % compared to 37 % for the BM group (p-value <0.001). CRS grades were distributed as follows: Grade 1 occurred in 74 % of PBSC recipients versus 34 % for BM (p-value <0.001), Grade 2 in 14 % for PBSC and 0 % for BM (p-value <0.001), and Grade 3 and Grade 4 were both seen in 1–2 % for both groups. In the subgroup analysis stratified by conditioning intensity, neutrophil engraftment (17 days versus 18 days; p-value = 0.017) was faster with PBSC compared to BM grafts and no statistically significant association was noted in rates of acute or chronic GvHD, NRM, relapse, DFS or OS among the myeloablative transplant recipients (n = 55). Among the RIC transplant recipients, no statistically significant differences were noted in neutrophil and platelet engraftment, acute GvHD, NRM, Relapse, DFS, and OS between the BM and PBSC groups (Table 3).