Alemtuzumab Induction and Tacrolimus Monotherapy in Pancreas Transplantation: One- and Two-Year Outcomes

Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1-16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin-induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76-1137 days (mean 572 days). One-year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first-time pancreas transplantation.

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“…From 1987From to 2004, about 5% of all pancreas transplants were retransplants (1). (16,(19)(20)(21)(22) …”

Section: Thrombosis Accounts For More Than One-half Of These Technimentioning

confidence: 99%

Immediate Retransplantation for Pancreas Allograft Thrombosis

Hollinger

Powelson²,

Mangus³

et al. 2009

American Journal of Transplantation

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“…However, the direct, nonimmunosuppressive toxicities of chronic calcineurin and steroid use, such as hypertension (3,4), diabetes (5), hyperlipidemia (6,7) and renal dysfunction (8) (10,11). Although initially approved for use in chronic lymphocytic leukemia, there is a growing body of literature describing the off label use of alemtuzumab as induction therapy in kidney (10,(12)(13)(14)(15)(16)(17), kidney/pancreas (18)(19)(20), pancreas (21,22), liver (23,24), intestine (25,26) and lung (11) transplantation. With the profound and prolonged lymphocyte depletion achieved with alemtuzumab, most of these studies have utilized alemtuzumab induction to facilitate a reduction in maintenance immunosuppression either with or without calcineurin inhibitors (CNIs) (27,28).…”

Section: Introductionmentioning

confidence: 99%

Alemtuzumab Induction Prior to Cardiac Transplantation with Lower Intensity Maintenance Immunosuppression: One-Year Outcomes

Teuteberg

Shullo

Zomak

et al. 2010

American Journal of Transplantation

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Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1-3 (8.5 vs. 12.9), month 4-6 (10.2 vs. 13.0), month 7-9 (10.2 vs. 11.9) and month 10-12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids.

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“…2 It is approved for use in chronic lymphocytic leukemia (CLL) 3 but is also used in non-Hodgkin lymphoma, 4 T-cell malignancies, 4 rheumatoid arthritis, 5 vasculitis, 6 scleroderma, 7 eosinophilia, 8 and prevention of graft-versus-host-disease and graft rejection in bone marrow, 9 stem cell, 10 and solid organ transplantation. [11][12][13] Alemtuzumab administration is sometimes associated with a cytokine-release syndrome, which can include pyrexia, headaches, nausea, urticaria, and rigors. 2 Myelotoxicity may result in anemia, thrombocytopenia, and neutropenia.…”

Section: Introductionmentioning

confidence: 99%

Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab

Ambrose¹,

Morel²,

Warrens

2009

Blood

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Neutropenia is a recognized adverse event in patients treated with the humanized anti-CD52 monoclonal antibody alemtuzumab. However, as it is widely believed that neutrophils do not express CD52, the etiology of alemtuzumab-associated neutropenia is unclear. We have found that neutrophils express both mRNA coding for CD52 and the protein itself on the cell surface. We confirmed cell-surface expression using 3 different anti-CD52 antibodies, and note that neutrophils express lower levels of CD52 than lymphocytes and eosinophils. Further, incubation of alemtuzumab with neutrophils results in dose-dependent, complement-mediated lysis in the presence of both heterologous and autologous complement. These data offer an explanation for the etiology of alemtuzumab-associated neutropenia. In a climate of increased use of alemtuzumab in leukemia and other disease states, as well as in transplantation, these data highlight the need for increased vigilance of emerging neutropenia in patients treated with alemtuzumab. (Blood. 2009; 114:3052-3055) IntroductionNeutropenia is a recognized adverse event in patients treated with alemtuzumab, a humanized monoclonal CD52-specific antibody. 1 A highly lytic antibody, alemtuzumab mediates cytotoxicity by antibody-dependent cell-mediated cytotoxicity and potent activation of human complement. 2 It is approved for use in chronic lymphocytic leukemia (CLL) 3 but is also used in non-Hodgkin lymphoma, 4 T-cell malignancies, 4 rheumatoid arthritis, 5 vasculitis, 6 scleroderma, 7 eosinophilia, 8 and prevention of graft-versus-host-disease and graft rejection in bone marrow, 9 stem cell, 10 and solid organ transplantation. [11][12][13] Alemtuzumab administration is sometimes associated with a cytokine-release syndrome, which can include pyrexia, headaches, nausea, urticaria, and rigors. 2 Myelotoxicity may result in anemia, thrombocytopenia, and neutropenia. 14 In particular, postalemtuzumab neutropenia occurs in both fludarabinerefractory 1 and treatment-naive 14 CLL. The etiology of postalemtuzumab neutropenia, and its associated morbidity and mortality, is poorly understood. 15 The obvious mechanism for postalemtuzumab neutropenia would be through neutrophil CD52 expression. However, it is widely believed that neutrophils do not express CD52, 11 unlike T and B lymphocytes, natural killer (NK) cells, monocytes, dendritic cells, and male reproductive tract cells. 2 Within the granulocyte population, it has been reported that eosinophils, but not neutrophils, express CD52. 16 We revisited this question and have shown that neutrophils contain CD52 mRNA, express surface CD52, and are susceptible to complement-mediated lysis in the presence of alemtuzumab. The level of CD52 on neutrophils is lower than on eosinophils and T and B lymphocytes, which could be why it has been difficult to detect. Methods Cell isolationBlood was separated into peripheral blood mononuclear cells (PBMCs) and granulocytes using density-gradient centrifugation over Polymorphprep (Axis-Shield). RPMI-1640 with 100 U/mL pe...

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Alemtuzumab Induction and Tacrolimus Monotherapy in Pancreas Transplantation: One- and Two-Year Outcomes

Abstract: A single dose of perioperative alemtuzumab followed by daily tacrolimus monotherapy provides effective immunosuppression for pancreas transplantation, but the optimal use of this drug combination is not yet clear.

Cited by 50 publications

References 22 publications

Immediate Retransplantation for Pancreas Allograft Thrombosis

Immediate Retransplantation for Pancreas Allograft Thrombosis

Alemtuzumab Induction Prior to Cardiac Transplantation with Lower Intensity Maintenance Immunosuppression: One-Year Outcomes

Neutrophils express CD52 and exhibit complement-mediated lysis in the presence of alemtuzumab

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