Reduced-intensity conditioning hematopoietic cell transplantation is an effective treatment for patients with SLAM-associated protein deficiency/X-linked lymphoproliferative disease type 1

Rebecca A Marsh, Jack J Bleesing, Shanmuganathan Chandrakasan, Michael B Jordan, Stella M Davies, Alexandra H Filipovich
Biology of Blood and Marrow Transplantation 2014, 20 (10): 1641-5
X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune deficiency caused by mutations in SH2D1A. Allogeneic hematopoietic cell transplantation (HCT) is often performed because of the morbidity and mortality associated with XLP1. There is limited experience using reduced-intensity conditioning (RIC) regimens for these patients. Here we report our 8-year single-center experience. Sixteen consecutive patients diagnosed with XLP1 underwent allogeneic HCT between 2006 and 2013 after a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan. Patient phenotypes included hemophagocytic lymphohistiocytosis (HLH) after Epstein-Barr virus (n = 5) or human herpesvirus 6 (n = 1), macrophage activation syndrome (n = 1), interstitial pneumonitis and encephalitis (n = 1), B cell lymphoma (n = 8), and hypogammaglobulinemia (n = 2). One patient was asymptomatic. Fourteen of 16 patients received 8/8 HLA-matched unrelated or related bone marrow grafts, whereas 2 patients received mismatched unrelated grafts. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methylprednisolone and cyclosporine in all but 1 patient, who additionally received methotrexate. All patients had hematopoietic recovery. There were no cases of hepatic veno-occlusive disease or pulmonary hemorrhage. One patient (6%) developed acute GVHD and later also developed chronic GVHD (6%). Five patients (31%) developed mixed chimerism. Only 1 patient with mixed chimerism (6%) experienced a decline of donor chimerism to less than 50% but returned to full donor chimerism after infusion of donor lymphocytes and a CD34(+) selected stem cell boost. Infectious complications were frequent, particularly viral reactivation. One-year survival estimated by Kaplan-Meier analysis was 80%, with long-term survival estimated at 71%. Survival was similar for patients with or without a history of HLH (86% versus 75%, respectively, P = .70). There were no occurrences of lymphoma or HLH after HCT. RIC HCT with alemtuzumab, fludarabine, and melphalan is an effective treatment for patients with XLP1, offering good survival rates regardless of prior disease manifestations, including HLH.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.