Malignancies after Hematopoietic Cell Transplantation for Primary Immune Deficiencies: A Report from the Center for International Blood and Marrow Transplant Research

Abstract

We describe the incidence of malignancy in patients with primary immunodeficiency disorders (PIDD) following hematopoietic cell transplantation (HCT). From the Center for International Blood and Marrow Transplant Research, 2266 PIDD patients who had undergone allogeneic HCT between 1968 and 2003 were identified. Patient, disease and transplant factors for development of malignancy were examined and pathology reports for reported malignancies reviewed independently by a pathologist for confirmation. The incidence of malignancy was highest for Wiskott-Aldrich syndrome (3.3%) with an overall incidence of 2.3% for PIDD. Post-HCT malignancy was confirmed for 52 of 63 reported cases. Forty-five of 52 patients developed a lymphoproliferative disorder (PTLD) at a median of 3 months post-HCT. Of these, 26 had received T-cell depleted (TCD) bone marrow. Three patients who developed myelodysplastic syndrome had received TCD marrow and total body irradiation. Three patients developed a solid tumor. Patients with PIDD are at a relatively low risk of developing malignancies post-HCT compared to their historical risk of cancer. The most frequent malignancy or lymphoproliferative disorder was early-onset PTLD. As in other HCT recipients, TCD appears to correlate with PTLD development. Our results lend support to the hypothesis that immune reconstitution in PIDD following HCT leads to a decrease in cancer risk.

Hematopoietic Stem Cell Transplantation for Severe Combined Immunodeficiency

“…In patients transplanted for a variety of primary immunodeficiencies, true secondary malignancies occurred with an incidence of only 0.2% at 5-15 years. (43) However, late mortality (>2 years post-HSCT) due to infection, organ failure, and chronic GVHD still occurred in 7% of patients. (44)…”

Unresolved issues in hematopoietic stem cell transplantation for severe combined immunodeficiency: Need for safer conditioning and reduced late effects

“…21 The cumulative incidence of second malignancies, including lymphoproliferative disorders, was 2% in patients with SCID at 5 and 10 years after transplantation and 3% at 15 years after transplantation. 22 When lymphoproliferative disorders and lymphomas were excluded, only 2 of 1050 patients with SCID followed long-term had a solid tumor: 1 brain tumor and another desmoplastic squamous cell carcinoma of the foot. 22 …”

“…22 When lymphoproliferative disorders and lymphomas were excluded, only 2 of 1050 patients with SCID followed long-term had a solid tumor: 1 brain tumor and another desmoplastic squamous cell carcinoma of the foot. 22 …”

Fatal Outcome Despite Full Lympho-Hematopoietic Reconstitution After Allogeneic Stem Cell Transplantation in Atypical Ataxia Telangiectasia

“…There are reports of EBV negative PTLD in solid organ transplants [8]; additionally, a retrospective analysis of patients with primary immunodeficiencies undergoing SCT revealed that lymphoproliferative disorders, predominantly PTLD, constituted the majority of malignancies occurring after transplantation [9]. However, histological examination did not reveal any signs of lymphoproliferation.…”