Risk of RBC alloimmunization in multiple myeloma patients treated by Daratumumab.

BACKGROUND: Daratumumab (DARA) is a human monoclonal antibody for the treatment of multiple myeloma (MM). DARA binds to CD38 on RBCs and interferes with detection of RBC alloantibodies. The objective of this study was to evaluate the risk of RBC alloimmunization in MM patients treated with DARA. MATERIALS AND METHODS: A retrospective study of the complete serological profile and transfusion history of 45 MM patients received transfusion and treated with DARA from July 2015 to December 2018 was undertaken. All cases with positive Ab screens were treated with DTT to identify RBC alloantibodies. RBC transfusion history was monitored between the first DARA dose to the last or extending to the first negative Ab screen after the last DARA dose if the Ab screen was ever positive. Forty-six MM patients received transfusion but not DARA were studied as control group. RESULTS: Totally 184 Ab screens were done on 45 patients transfused with ABO-Rh compatible RBCs, phenotypically matched units or both. None of them showed detectable alloantibodies after DTT treatment. The duration of Ab screening positivity varied markedly, ranging from 25 days to 5 months after the last dose. Two of 46 patients in the control group had preexisting alloantibodies but no new alloantibodies were detected during study period. CONCLUSIONS: Our results indicate that the risk of forming new RBC alloantibodies after transfusion in MM patients treated with current regimens is very low and no DARA-associated difference in the alloimmunization risk. No significant difference in alloimmunization is detected between ABO-Rh compatible and phenotypically matched transfusion.

Monoclonal B-cell lymphocytosis in healthy blood donors: an unexpectedly common finding.

Circulating monoclonal B cells may be detected in healthy adults, a condition called monoclonal B-cell lymphocytosis (MBL). MBL has also been identified in donated blood, but no systematic study of blood donors has been reported. Using sensitive and specific laboratory methods, we detected MBL in 149 (7.1%; 95% confidence interval, 6.0% to 8.3%) of 2098 unique donors ages 45 years or older in a Midwestern US regional blood center between 2010 and 2011. Most of the 149 donors had low-count MBL, including 99 chronic lymphocytic leukemia-like (66.4%), 22 atypical (14.8%), and 19 CD5(-) (12.8%) immunophenotypes. However, 5 donors (3.4%) had B-cell clonal counts above 500 cells per µL, including 3 with 1693 to 2887 cells per µL; the clone accounted for nearly all their circulating B cells. Four donors (2.7%) had 2 distinct MBL clones. Of 51 MBL samples in which immunoglobulin heavy chain (IGH)V-D-J genotypes could be determined, 71% and 29% used IGHV3- and IGHV4-family genes, respectively. Sequencing revealed 82% with somatic hypermutation, whereas 18% had >98% germ-line identity, including 5 with entirely germ-line sequences. In conclusion, MBL prevalence is much higher in blood donors than previously reported, and although uncommon, the presence of high-count MBL warrants further investigations to define the biological fate of the transfused cells in recipients.

Acquired factor V inhibitor in the setting of coronavirus disease 2019 infection.

Factor V inhibitors are a rare cause of life-threatening bleeding. We present a case of an acquired factor V inhibitor likely caused by coronavirus disease 2019 infection. Bleeding was manifested by severe anemia requiring frequent red-cell transfusion, left psoas muscle hematoma, and left retroperitoneal cavity hematoma. Factor V activity was less than 1% and the factor V inhibitor titer was 31.6 Bethesda units. Severe acute respiratory syndrome coronavirus 2 RNA testing of the nasopharynx was positive 2 weeks before presentation and continued to be positive for 30 days. The patient failed treatment with intravenous immunoglobulin and dexamethasone. Three cycles of plasmapheresis with fresh frozen plasma replacement resulted in correction of the bleeding and laboratory coagulopathy. This is the first reported case of a factor V inhibitor in a coronavirus disease 2019 patient and suggests that plasmapheresis may be a successful treatment strategy.

Flow Cytometric, Morphologic, and Laboratory Comparative Study in Patients With Leukocytosis and Cytopenia.

OBJECTIVES: We wanted to evaluate the effectiveness of flow cytometry immunophenotyping (FCI) as a screening test for patients with leukocytosis and cytopenia. METHODS: We identified 320 patients during August 2016 to December 2016 and evaluated FCI and morphology of peripheral blood smears (PBSs). RESULTS: The most common indications for FCI included history of hematologic malignancy (HHM, n = 126), leukocytosis (n = 80), and cytopenia (n = 53). Positive FCI rate was low with a range of 4.4% to 12.5% in patients with absolute neutrophilia regardless of HHM, if cases with circulating blasts were excluded. Patients with absolute lymphocytosis had a 93% positive FCI rate. Patients with HHM and pancytopenia showed a higher incidence of positive FCI findings than patients without HHM and with isolated cytopenia. PBS morphology correlated strongly with FCI (P = .0001). CONCLUSION: PBS evaluation is an accurate and cost-effective screening test. FCI for patients with mature neutrophilia and isolated cytopenia has a very low yield.

Fatal pulmonary embolism and pulmonary hemorrhage in lupus anticoagulant hypoprothrombinemia syndrome: a case report and review of literature.

: Lupus anticoagulant hypoprothrombinemia syndrome (LAHS) is a rare disorder characterized by development of lupus anticoagulant and antiprothrombin antibodies. The most common clinical manifestation is bleeding. Clinical management can be challenging due to the subtle balance between the bleeding and thrombotic tendencies. We report a novel case of LAHS in which the patient experienced the sequence of hemorrhage-thrombosis-hemorrhage before eventually dying of fatal pulmonary embolism and pulmonary hemorrhage. Specifically, she presented with multiple gastrointestinal bleeding episodes, followed by multifocal subdural hematomas, pulmonary embolism after normalization of prothrombin activity levels with immunosuppression, and finally with fatal pulmonary hemorrhage after enoxaparin treatment for pulmonary embolism. This case illustrates the importance of recognizing early minor bleeding episodes, and detecting specific antiprothrombin antibodies, in the diagnosis of LAHS. Furthermore, it highlights the complex challenge of normalizing prothrombin activity levels while at the same time preventing medical complications.

Monoclonal B-cell lymphocytosis in blood donors.

Monoclonal B-cell populations have been detected in the peripheral blood of apparently healthy individuals by flow cytometry. In 2005, the term monoclonal B-cell lymphocytosis (MBL) was proposed to describe these findings. MBL may be immunophenotypically similar to chronic lymphocytic leukaemia (CLL) and, like CLL, the prevalence is higher in males and older individuals. We studied the prevalence of MBL in blood donors from the Midwestern United States. Samples from 5141 donors were examined and seven (0.14%) were found to have immunophenotypic characteristics of MBL or CLL. Immunoglobulin heavy chain analysis yielded monoclonality or oligoclonality. Prior and subsequent to the study, an additional undetermined number of blood donors were screened and seven of these expressed immunophenotypic characteristics of MBL or CLL. We thus found a total of 14 healthy blood donors with monoclonal expansions of B-lymphocyte populations. Of these, 12 were presumptively classified as MBL and two as CLL. All but two of the donors were male; the mean age was 59 years. The clinical importance of these findings with regard to transfusion medicine has not been established.

Immature platelet fraction as a predictor of platelet recovery following hematopoietic progenitor cell transplantation.

The immature platelet fraction (IPF) as determined by the Sysmex XE-2100 is a rapid automated measure of the least mature component of the platelet population and is thought to correlate with thrombopoietic activity of the marrow. We investigated the ability of IPF to predict platelet recovery following hematopoietic progenitor cell (HPC) transplantation. IPF was compared to standard parameters of hematopoietic recovery, including the immature reticulocyte fraction (IRF), an early predictor of recovery. Fifty patients undergoing peripheral blood HPC transplantation (38 autologous and 12 allogeneic) were followed daily for 11 to 28 days after transplantation with measurement of IPF, IRF, absolute neutrophil counts (ANC) and platelet counts. Mean days to recovery for IPF was 3.1 days less than for platelet count (P <.0001), 3.8 days less than for ANC (P <.0001), and 0.6 days less than for IRF (P = .0477). IPF recovered at least 1 day prior to platelet count in 79% (38 of 48) of patients, and was followed by platelet count recovery within 1 to 12 days (mean, 4.1 days). When autologous and allogeneic patient groups were analyzed separately, IPF recovered significantly earlier than platelet count and ANC in both groups (P <.0001). Thrombopoietin (TPO) levels in 5 patients receiving transplants correlated with IPF; however, this appeared to be secondary to an inverse correlation of both TPO and IPF with platelet count. IPF is comparable to IRF as one of the earliest predictors of hematopoietic recovery following peripheral blood HPC transplantation. IPF could potentially be useful as a predictor of platelet recovery in other bone marrow failure syndromes.