Red cell aplasia and autoimmune hemolytic anemia following immunosuppression with alemtuzumab, mycophenolate, and daclizumab in pancreas transplant recipients.
OBJECTIVE
Acquired red cell aplasia (RCA) is a rare disorder and can be either idiopathic or associated with certain diseases, pregnancy, or drugs. In exceptionally rare cases, it has been reported to co-exist with other autoimmune cytopenias. We report a high incidence of RCA and autoimmune hemolytic anemia (AIHA) in pancreas transplant recipients on alemtuzumab-based maintenance therapy.


METHODS
Between February 2003 and July 2005, 357 pancreas transplant recipients were treated with immunosuppressive regimens containing the lymphocyte-depleting antibody alemtuzumab, the T-cell activation inhibitor daclizumab, and the anti-metabolite mycophenolate mofetil (MMF). We retrospectively reviewed medical records, blood bank data and bone marrow biopsy specimens of patients with a Transplant Information Services database diagnosis of RCA and AIHA from February 2003 to November 2005.


RESULTS
Severe RCA, AIHA, and idiopathic thrombocytopenic purpura (ITP) occurred independently or in combination, in 20 out of 357 (5.6%) pancreas transplant recipients, 12 to 24 months following the initiation of the aforementioned immunosuppressive regimens. Severe opportunistic infections developed late in 14/20 (70%) of these patients. Atypical morphologic features, including variable dysgranulopoiesis, variable megakaryocytic hyperplasia with normal or low peripheral platelet counts, and atypical lymphoid aggregates were found in bone marrow trephine sections of 11 patients in whom the diagnosis of RCA was made.


CONCLUSIONS
We hypothesize that the combination of alemtuzumab, daclizumab and MMF can result in immune dysregulation thereby permitting autoantibody formation. Because the use of these three immune suppressants is becoming increasingly common, it is important to recognize the severe hematologic complications that can arise.
Elimelakh
Milena
M
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA. elime002@umn.edu
Dayton
Vanessa
V
Park
Katharine S
KS
Gruessner
Angelika C
AC
Sutherland
David
D
Howe
Robert B
RB
Reding
Mark T
MT
Eastlund
Ted
T
van Burik
Jo-Anne
JA
Singleton
Timothy P
TP
Gruessner
Rainer W
RW
Key
Nigel S
NS
D000328:Adult; D000074323:Alemtuzumab; D000744:Anemia, Hemolytic, Autoimmune / Q000139:chemically induced* / Q000453:epidemiology; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000453:epidemiology; D001853:Bone Marrow / Q000473:pathology; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation / Q000706:statistics & numerical data; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009894:Opportunistic Infections / Q000453:epidemiology / Q000209:etiology; D016035:Pancreas Transplantation / Q000706:statistics & numerical data; D010865:Pilot Projects; D011183:Postoperative Complications / Q000139:chemically induced* / Q000453:epidemiology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced / Q000453:epidemiology; D012010:Red-Cell Aplasia, Pure / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D000077561:Daclizumab; D009173:Mycophenolic Acid