High Prevalence of Dapsone-Induced Oxidant Hemolysis in North American Stem Cell Transplant Recipients without Glucose-6-Phosphate-Dehydrogenase Deficiency.

Dapsone (4-4'-diaminodiphenylsulfone) is commonly used for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in immunocompromised patients. Oxidant hemolysis is a known complication of dapsone, but its frequency in adult patients who have undergone stem cell transplantation (SCT) for hematologic malignancies is not well established. We report a high prevalence of hemolytic anemia associated with dapsone use in SCT patients in the absence of glucose-6-phosphate dehydrogenase (G6PDH) deficiency.

We retrospectively analyzed laboratory data from 30 SCT (29 Caucasian and 1 African-American; 15 male and 15 female) patients receiving dapsone (100 mg orally daily) for PCP prophylaxis to determine the frequency of oxidant hemolysis. All patients had undergone allogeneic (n = 27) or autologous SCT (n = 3) for hematological malignancy or aplastic anemia. Peripheral blood (PB) smears were reviewed in a blinded fashion for the presence of morphologic features of oxidant hemolysis (multiple bite cells in each high power field), with PB smears from the same patient group while not on dapsone serving as controls. Additional demographic and laboratory data, including G6PDH enzyme activity screening test, hemoglobin, reticulocyte count, lactate dehydrogenase and bilirubin levels, were collected from chart review.

29 patients had normal G6PDH activity (results were not available for 1 patient). 38 PB smears were obtained while on dapsone (some patients had more than one bone marrow evaluation). 30 (79%) PB smears from 26 (87%) patients had morphologic evidence of overt oxidant hemolysis. This was significantly higher than in the controls, in which 5/22 (23%) PB smears had morphologic features of oxidant hemolysis (p<0.001, Fisher's exact test). Hemoglobin levels were lower in the dapsone group, compared to the controls (10.0 vs. 12.5 g/dL, p=0.012). Mean LDH (507 IU) and direct bilirubin (1.6 g/dL) were also increased in the patients on dapsone. None of the patients had laboratory signs of hemolysis while not on dapsone.

Dapsone-induced oxidant hemolysis in SCT patients is 20-fold higher than the reported rate in HIV-infected patients receiving this agent. This high prevalence in patients without G6PDH deficiency suggests the coexistence of other sources of oxidant stress specific to this patient cohort.

Bredeson:Esai: Honoraria.