Risk factors for red blood cell alloimmunization in patients with hematologic malignancy.

INTRODUCTION: Patients with hematologic malignancy have a higher risk of developing red blood cell (RBC) alloimmunization which can delay blood transfusion. Information on the risk factors for alloimmunization in this group is still limited. This study aimed to determine the prevalence and predictors of RBC alloimmunization among these patients. MATERIALS AND METHODS: Electronic medical records of the patients with acute myeloid leukaemia (AML), acute lymphoid leukaemia (ALL), multiple myeloma (MM) and lymphoma from a tertiary care hospital between January 2018 and December 2022 were retrospectively reviewed. Clinical, demographic and transfusion history data of the included patients were analysed. RESULTS: Of the 983 patients with hematologic malignancy, 798 were included in the study. The prevalence of RBC alloantibodies in this population was 4.8% (38 patients). The alloimmunization rate of each subgroup was as followed: AML 9.1%, ALL 2.9%, MM 3.8% and lymphoma 2.5%. The most common alloantibodies were anti-Mia, anti-E and anti-Lea. The majority (29/38, 76.3%) of alloimmunization had a single alloantibody. RBC autoantibody was detected in 10 patients. The detection of autoantibodies and having AML were independently associated with RBC alloimmunization (adjusted odds ratio [aOR] 13.41, 95% confidence interval [CI] 2.00-89.72, p = 0.007 and aOR 11.44, 95% CI 2.02-64.72, p = 0.006, respectively). CONCLUSION: The prevalence of RBC alloimmunization in the patients with hematologic malignancy was 4.8%. The alloimmunization rate of the AML subgroup was higher than those of other hematologic malignancies. The detection of autoantibodies and the AML diagnosis were identified as potential risk factors for RBC alloimmunization.

Combined peripheral blood monocyte count and white blood cell count as a guide for successful one-day autologous peripheral blood stem cell collection.

INTRODUCTION: Peripheral blood stem cells (PBSCs) are the most common source of stem cell transplantation, which depends on an adequate number of CD34+ cells. Although pre-apheresis CD34+ cell count is a standard guide for the collection, it is not always available. This study aimed to evaluate complete blood count parameters for predicting successful one-day autologous PBSC collection. METHODS: Data from the patients who underwent autologous PBSC collection at a tertiary care hospital were retrospectively reviewed. RESULTS: There were 123 patients (185 leukapheresis procedures). Successful PBSC collection (CD34+ cells ≥4.0 × 106 cells/kg) was obtained in 85 patients (69.1%), of which 55 (44.7%) were successfully obtained on the first day. The median CD34+ collection efficiency was 44.1%. The mean platelet loss during apheresis was 39.9%. The adverse event rate was 18.9%. Patients in whom PBSCs were collected within one day were less likely to experience adverse effects related to leukapheresis. Pre-apheresis CD34+ cells ≥10 cells/µLand combined white blood cell (WBC) counts ≥5 × 109/L and/or monocyte ≥10% were independently associated with the successful one-day PBSC collection (adjusted odds ratio 24.06, 95% confidence interval [CI] 5.30-109.10, p < 0.001; and 6.94, 95% CI 1.35-35.79, p = 0.021, respectively). Only pre-apheresis CD34+ cells had a strong correlation with the total stem cell yield. CONCLUSIONS: To reduce the complication of leukapheresis, the combined pre-apheresis WBC ≥5 × 109/L and/or monocyte ≥10% is a practical parameter to initiate a successfully one-day PBSC collection with or without pre-apheresis CD34+ cell results.

Prognostic factors and impact of CMV reactivation on acute myeloid leukemia patients after HLA-matched myeloablative allogeneic stem cell transplantation in a high CMV prevalence country

ABSTRACT Introduction: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population. Methods: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients. Results: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%. Conclusions: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.

Prognostic factors and impact of CMV reactivation on acute myeloid leukemia patients after HLA-matched myeloablative allogeneic stem cell transplantation in a high CMV prevalence country.

INTRODUCTION: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population. METHODS: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients. RESULTS: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%. CONCLUSIONS: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.

Detection of Red Blood Cell Membrane Proteins in Myelodysplastic Syndromes Using Eosin-5-Maleimide (EMA) Staining by Flow Cytometry.

Background: Eosin-5-Maleimide (EMA)-based flow cytometry binds to red blood cell (RBC) membrane-associated proteins which can be used to detect red blood cell (RBC) membrane disorders. Myelodysplastic syndromes (MDS) are stem cell disorders resulting in ineffective hematopoiesis which is commonly present with anemia and erythroid dysplasia. Objectives: We aimed to study RBC membrane defects in MDS using flow cytometry for EMA staining. Methods: We enrolled anemic patients who were diagnosed with low-risk MDS (R-IPSS score ≤ 3.5), RBC membrane disorders [hereditary spherocytosis (HS) and Southeast Asian ovalocytosis (SAO)], and normal controls. Complete blood count (CBC) and flow cytometry for EMA staining were performed. Results: There were 16 cases of low-risk MDS, 6 cases of RBC membrane disorders, and 15 control cases. Mean fluorescence intensity (MFI) of EMA binding test in the RBC membrane disorders was significantly lower than controls (17.6 vs. 24.3, p < 0.001), but the EMA binding test in the low-risk MDS was not significantly different than the controls (26.5 vs. 24.3, p = 0.08). Conclusion: the RBC membrane defect in low-risk MDS was not demonstrated as having detection ability using EMA binding test with flow cytometry.

High B-cell activating factor levels in multi-transfused thalassemia patients.

OBJECTIVES: To assess the associations between B-cell activating factor (BAFF) and alloimmunisation in multi-transfused thalassemia. BACKGROUND: Red blood cell (RBC) alloimmunisation is a complication of multi-transfused thalassemia. BAFF is promoting B cells that produce alloantibodies. METHODS/MATERIALS: Multi-transfused thalassemia, 15 years or older, were recruited in the cohort study. Alloantibodies and BAFF levels were analysed. RESULTS: Of 114 patients, the overall prevalence of RBC alloimmunisation was 29.8%. The most common alloantibodies were anti-E, anti-Mia and anti-c. BAFF levels were different among the three groups; the patients with baseline alloantibodies (median ± interquartile range 1251 ± 474 pg/ml), without alloantibodies (1098 ± 453) and healthy controls (719 ± 306), p < 0.001. The BAFF level was elevated in the >25 years old patients (vs. the <25, p = 0.011) and the buffy-coat-reduced blood recipients (vs. the pre-storage leukocyte-depletion, p = 0.005). Absolute lymphocyte count was higher in the patients without baseline alloantibodies (vs. with baseline alloantibodies, p = 0.049) and the splenectomised patients (vs. the non-splenectomised patients, p < 0.001). Of the 72 patients without baseline antibodies, four who developed new antibodies showed no statistically different BAFF levels compared with those without new antibodies after 40-month follow-up (1296 ± 734 vs. 1062 ± 460, p = 0.491). In multivariate analysis, BAFF to absolute lymphocyte ratio was independently associated with RBC alloimmunisation (odds ratio 3.07, 95% confidence interval 1.124-8.369, p = 0.029). CONCLUSION: B-cell activating factor (BAFF) levels were elevated in multi-transfused thalassemia and the BAFF to absolute lymphocyte ratio was associated with red blood cell (RBC) alloimmunisation.

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors.

Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n = 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n = 55) and controls (n = 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD.

A case of nearly mistaken AB para-Bombay blood group donor transplanted to a group 'O' recipient.

Unintentional ABO mismatch kidney transplantation can cause detrimental hyperacute rejection. We report the first successful ABO incompatible kidney transplantation from an AB para-Bombay donor to O recipient. At the initial evaluation, the donor's ABO type was discordance on the cell typing and serum typing, which typed to be 'O' as cell typing and 'AB' as serum typing. At the second investigation, it was confirmed that the donor had a unique, rare but not uncommon blood type AB para-Bombay which was incompatible with the recipient's blood group. The kidney transplantation was successfully performed by an ABO incompatible preconditioning, double filtration plasmapheresis (DFPP) and rituximab. The serum creatinine at 12 months post-transplantation was 1.3 mg/dL. The pathology of the kidney biopsy showed no signs of rejection.

Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial.

B cells are implicated in the pathophysiology of chronic graft-vs-host disease (GVHD), and phase 2 trials suggest that B cell depletion can treat established chronic GVHD. We hypothesized that posttransplantation B cell depletion could prevent the occurrence of chronic GVHD. We performed a 65-patient phase 2 trial of rituximab (375 mg/m(2) IV), administered at 3, 6, 9, and 12 months after transplantation. Rituximab administration was safe without severe infusional adverse events. The cumulative incidences of chronic GVHD and systemic corticosteroid-requiring chronic GVHD at 2 years from transplantation were 48% and 31%, respectively, both lower than the corresponding rates in a concurrent control cohort (60%, P = .1, and 48.5%, P = .015). There was no difference in relapse incidence, but treatment-related mortality at 4 years from transplantation was significantly lower in treated subjects when compared with controls (5% vs 19%, P = .02), and overall survival was superior at 4 years (71% vs 56%, P = .05). At 2 years from transplantation, the B-cell activating factor/B-cell ratio was significantly higher in subjects who developed chronic GVHD in comparison with those without chronic GVHD (P = .039). Rituximab can prevent systemic corticosteroid-requiring chronic GVHD after peripheral blood stem cell transplantation and should be tested in a prospective randomized trial.

Prevalence of monoclonal gammopathy of undetermined significance in Thailand.

Individuals with monoclonal gammopathy of undetermined significance (MGUS) develop multiple myeloma and related malignancies at the rate of 1% per year. Given differences in ethnicity, data on prevalence and risk factors of MGUS in Thai population will be helpful in understanding the pathogenesis of plasma cell disorders and designing an early cancer detection strategy. Subjects of 50 years or older were included. Demographic data and suspected risk factors were collected. Monoclonal proteins were detected using serum protein electrophoresis. Serum was obtained from 3,260 participants; 1,104 males (33.9%) and 2,156 females (66.1%). The median age was 57 years (range 50-93 years). Monoclonal proteins were detectable in 2.3% (95% confidence interval [CI] 1.8-2.8). M spikes were found in gamma- and beta-globulin regions in 50 (1.5%) and 25 (0.8%) subjects, respectively. The prevalence of MGUS in subjects 50-59, 60-69, and 70 years or older was 2.0% (41/1,975), 2.6% (22/851), and 2.8% (12/434), respectively. By multivariate analysis, MGUS was associated with living outside Bangkok (odds ratio 2.25, 95% CI 1.11-4.58). The overall prevalence of MGUS in the Thai population was 2.3%, which was lower than that in Western countries, but comparable to that in Japan.