In March 1996, an eight year old girl followed for sickle cell disease at BMC developed acute lymphoblastic leukemia (ALL), CNS negative but high risk on the basis of a t(1;19). Induction chemotherapy at MGH (one month) consisted of prednisone, vincristine, and L-asparaginase. This was followed by “intensification” (six months) with daunomycin, cyclophosphamide, methotrexate, and cytosine arabinoside. Since October 1996, however, she has received only weekly IV methotrexate (20 mg/m2) and oral 6-mercaptopurine (75 mg/m2), apart from intrathecal methotrexate and cytosine arabinoside every eight weeks. She remains in complete continuous remission. Prior to diagnosis of ALL, she had only rare vaso-occlusive pain crises, maintained a hematocrit of 20, and had <1% hemoglobin F. During early ALL chemotherapy, she was transfused pRBCs to maintain a hematocrit of>25. Despite this, she suffered an episode of pain crisis in April 1996 precipitated by her “day 28” bone marrow biopsy and aspirate. However, serial hemoglobin electrophoreses (Table) show that her level of hemoglobin F has risen into the 30% range during maintenance therapy, in concert with a stabilization of her untransfused hematocrit in the 25 to 30 range. A Kleihaur-Betke stain indicates a heterogeneous staining pattern. She has had no further pain crises, and has required no blood transfusions since early December 1996. These results demonstrate the efficacy of methotrexate-6-mercaptopurine in activating the gene for hemoglobin F.

Table 1 No caption available.
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