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X-linked Lymphoproliferative Syndrome Treatment & Management

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Nov 26, 2015

Medical Care

Currently, the only cure for X-linked lymphoproliferative disease (XLP) is allogeneic stem cell transplantation.[20]

As reported by the David Purtilo International XLP registry: Seven patients were treated with human leukocyte antigen (HLA)-identical allogeneic stem cell transplantation (sibling bone marrow: 5 patients; unrelated bone marrow: 1 patient; sibling umbilical cord: 1 patient). Four patients were alive with normal immune function more than 3 years after transplantation. Six patients developed acute grade I-II graft versus host disease. Three patients died within 100 days, 1 due to sepsis, 1 due to disseminated adenovirus infection, and 1 with multi-organ system failure.

The authors described a large cohort of 91 patients with genetically defined XLP1 collected from centers worldwide and reported characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients.[21] Survival after allogeneic HSCT was 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease.

However, survival fell to 50% in patients with hemophagocytic lymphohistiocytosis (HLH) as a feature of disease. Untransplanted patients had an overall survival of 62.5% with most on immunoglobulin replacement therapy, but the outcome was extremely poor (18.8%). The authors concluded that HSCT should be undertaken in all patients with HLH because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 was very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression.

Immune globulin

Patients with humoral immune deficits benefit from ongoing infusions of immune globulin.

Anti-CD20 rituximab

Milone et al administered the anti-CD20 antibody rituximab to 2 patients who presented with acute EBV infection.[4] Following treatment, both patients exhibited a complete resolution of symptoms and no longer demonstrated detectable EBV DNA within circulating lymphocytes. Moreover, neither patient has developed fulminant infectious mononucleosis (FIM) or lymphoma in more than 2 years of follow-up. These data suggest that the preemptive use of B-cell–directed therapy may reduce the morbidity and mortality of primary EBV infection in X-linked lymphoproliferative disease (XLP)–affected individuals.

Cytotoxic chemotherapy

Suggestions exist that treatment with cytotoxic chemotherapy during the acute IgM syndrome might be helpful in controlling proliferation of EBV-transformed B cells, as well as potentially activated cytotoxic lymphocytes that may be causing the severe tissue reactions observed in X-linked lymphoproliferative disease (XLP).

In a small number of cases, etoposide has been shown to lead to control of lymphocyte proliferation, at least temporarily. Limited anecdotal data confirm that this or other cytotoxic agents may be a successful treatment modality; however, further study is needed.[22]

Patients with B-cell lymphomas should be treated with the standard therapy for that disease. Special attention should be paid toward the potential infectious complications of these therapies.

Gene therapy

Rivat et al reported a preliminary study in mice in which the immune function defects of X-linked lymphoproliferative syndrome were corrected by lentiviral vector-mediated gene transfer of SH2D1A into autologous hematopoietic stem cells.[23]



Consultation by a genetic counselor could assist the family, if available.

Contributor Information and Disclosures

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.


Doris Ponce, MD Fellow, Department of Hematology/Oncology, New York Medical College

Doris Ponce, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.


M Wayne Saville, MD Associate Professor of Clinical Medicine, University of California at San Diego; Director, Hematology and Oncology, Global Medical Affairs, Biogen Idec, Inc

M Wayne Saville, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and Sigma Xi

Disclosure: Nothing to disclose.

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