Successful treatment of severe immune hemolytic anemia after allogeneic stem cell transplantation with bortezomib: report of a case and review of literature

Abstract

Background: Immune hemolytic anemia is a well-known complication after allogeneic hematopoietic stem cell transplantation (HSCT). Posttransplant hemolytic anemia results in increased red blood cell transfusions and medical sequelae including iron overload.

Case report: We present a case report of immune hemolytic anemia that occurred after allogeneic HSCT from an ABO major-mismatched, HLA-matched unrelated donor. The patient had high anti-donor A type antibodies that were unresponsive to treatment with steroids and rituximab, resulting in persistent transfusion dependence. A detailed time course of anti-A titers, plasma cell content of the marrow, and B-cell content of the blood is presented. Treatment with bortezomib, a protease inhibitor, eliminated residual host-type plasma cells secreting anti-A and restored normal donor-derived erythropoiesis.

Conclusion: This report, and a review of literature for treatment of immune hemolytic anemia after allogeneic HSCT, supports the utility of bortezomib as plasma cell-targeted therapy in this setting.

© 2014 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Figures

Fig 1

Clinical course of the reported patient with immune hemolytic anemia. (A) Treatment course of steroids (black bars), rituximab (black arrows), and bortezomib (orange arrows). The height of the black bars shows the relative dose of steroids. (B) Graph of Hb (black dashed line) and reticulocyte percentage (red solid line) with timing of RBC transfusions (black arrows). (C) Graph of total IgG (black solid line with diamonds) and IgM (black dashed line with triangles) and anti-A IgG titers (green solid line with diamonds) and anti-A IgM titers (green dashed line with triangles). Semiquantitative titration of anti-A of both the IgM and the IgG subclasses were performed using standard methods. Briefly, 2% suspensions of A1 reagent RBCs were mixed with patient plasma in test tubes. For IgM detection, after 15 minutes of incubation at room temperature the samples were centrifuged and macroscopic agglutination was quantified; for IgG, samples were incubated for 60 minutes at 37°C, washed to remove unbound antibody, incubated with anti-human IgG, and then centrifuged to score agglutination. (D) Numbers of CD19+ cells in blood (black dashed line) were assessed by flow cytometry, and plasma cells percentage score for nucleated cells in bone marrow (blue solid line) were estimated blinded to case identical number and date.

Fig 2

Histologic sections of marrow from the patient with immune hemolytic anemia. Tissue sections were immune stained with anti-CD138 MoAb, and CD138+ cells were visualized after secondary staining with a horseradish peroxidase–labeled secondary antibody. Immunohistochemical analysis for CD138+ plasma cells present in marrow biopsies obtained on Day –22 (A), Day +97 (B), Day +160 (C), and Day +249 (D) with respect to the day of transplant are shown. Overall cellularities of the marrow at the times represented in A, B, C, and D were 40, 60, 50, and 15%.