Abstract 2488

Hairy cell leukemia (HCL) is a B-cell malignancy which is thought to originate in most patients after the B-cell contacts antigen. To determine whether certain HLA types are preferentially expressed in HCL, HLA class I and class II allele frequencies at low resolution were collected from 247 HCL patients including 233 Caucasian, 5 Black, 5 Hispanic, 2 Asian and 2 Hawaiian/Pacific Islanders. Out of 494 total alleles from the 247 patients, the most frequent were HLA-A*02 (145, 29%), HLA-B*07 (58, 12%), HLA-C*07 (141, 29%), and HLA-DRB1*11 (76, 15%). In comparison with normal donors, only HLA-DRB1*11 was preferentially expressed in HCL, with a population frequency among the 233 Caucasians of 70 (30%), compared to 17% of a database of USA Caucasians (n=61655, p<0.0001) and 12–21% in 8 other smaller USA Caucasian databases (n=194–8525, p=0.01, 0.005, p<0.0001 for 6 others).

Because it was recently reported that HLA-DRB1*11 is a strong risk factor for acquired ADAMTS13 deficiency-related thrombotic microangiopathy, HCL patients who had hemolytic uremic syndrome (HUS) after anti-CD22 recombinant immunotoxin BL22 were examined for HLA expression at the DRB1 locus. BL22 was previously reported to be associated in HCL with a 12% risk of completely reversible grade 3–4 HUS mainly during the 2nd or 3rd retreatment cycle. We found that of 49 HCL patients treated with at least 2 cycles of BL22, most (71%) of 7 HCL patients with HUS expressed HLA-DRB1*11, compared to only 21% of 42 without HUS (p=0.015). Even when considering all 66 evaluable HCL patients who received BL22, including the 17 who received just 1 cycle, expression of HLA-DRB1*11 was more frequent in those with compared to without HUS (63% of 8 vs 24% of 58 patients, p=0.038).

In the poor-prognosis variant of HCL, termed HCLv, we found that the most common HLA-DRB1 gene expressed was HLA-DRB1*04, found in 19 (56%) of 34 patients, compared to 30% of the normal USA Caucasian database (n=61655, p=0.002) and 27–37% in the 8 smaller databases mentioned above (p values 0.016 and 0.001–0.01). HLA-DRB1*04 expression was recently reported to be significantly reduced in patients with idiopathic thrombotic microangiopathy. In BL22-associated HUS in HCL, DRB1*04 expression was not increased and none had HCLv.

Moxetumomab pasudotox, an affinity-matured version of BL22, binds with 14-fold higher affinity to CD22 due to mutations in the CDR3 domain of the heavy chain, and was recently reported in 28 HCL patients to be associated with only 2 cases of transient grade 2 HUS, defined as grade 1 creatinine and platelet abnormalities. No HUS was observed in 20 additional HCL patients treated. Despite the similarity in the population incidences of HLA-DRB1*11 in those receiving moxetumomab pasudotox and BL22 (35% vs 29%), the grade 3–4 HUS risk was significantly lower with moxetumomab pasudotox than with BL22 (p=0.02). We conclude that 1) HLA-DRB1*11 is preferentially expressed in HCL, 2) HLA-DRB1*04 is preferentially expressed in HCLv, and 3) HLA-DRB1*11 constitutes a potential marker in HCL for susceptibility to HUS from BL22, but not from moxetumomab pasudotox, possibly because the latter molecule binds more specifically to CD22 and avoids HUS.


Off Label Use: BL22 and Moxetumomab Pasudotox are experimental agents for CD22+ malignancies. Pastan:NIH: Coinventor on NIH patents for BL22 and Moxetumomab, Coinventor on NIH patents for BL22 and Moxetumomab Patents & Royalties. Kreitman:NIH: Coinventor on NIH patents for BL22 and Moxetumomab, Coinventor on NIH patents for BL22 and Moxetumomab Patents & Royalties.

Author notes


Asterisk with author names denotes non-ASH members.