Treatment of High-Risk Pre-B Acute Lymphoblastic Leukemia in a Fanconi Anemia Patient with Reduced-Intensity Chemotherapy

Fanconi anemia (FA) is an inherited bone marrow failure syndrome that is associated with multiple congenital anomalies and a predisposition to cancer, primarily acute myeloid leukemia and oropharyngeal cancers. Acute lymphoblastic leukemia (ALL) has also rarely been reported. Because of their rarity, there is no consensus on how to treat leukemias when they develop. We report an 8-year old boy with FA, who developed high-risk pre-B ALL due to an unfavorable DNA-index, and monosomy 7. Patient received low-risk ALL induction chemotherapy (vincristine 1.5 mg/m² iv, weekly × 4; prednisone 40 mg/m²/day orally for 28-days then tapered; Peg-asparaginase 2500 IU/m² on day 3, intrathecal cytarabine on day 0, intrathecal methotrexate on day 14). Patient went in remission promptly by day 14. The patient developed liver dysfunction and a fungal infection, which were treated accordingly. Following induction, the patient developed prolonged myelosuppression that required regular platelet and PRBC transfusions. He was treated with non-myelosuppressive post-induction chemotherapy for 6 months prior to stem cell transplantation (SCT). His therapy consisted of two doses of Peg-asparaginase and two courses of oral dexamethasone for 5 days each. During this period, serial bone marrow biopsies showed that the patient remained in remission. Moreover, cytogenetic analysis showed a disappearance of monosomy 7. Because the patient had no matched donor, he was given T-cell depleted haploidentical SCT from his mother. The patient’s lymphoid and myeloid donor cell chimerism was 100 % on day +47 of SCT. The patient’s condition was complicated by a severe adenovirus infection to which he succumbed on day +60 post SCT. In conclusion, there is no standard chemotherapy treatment for patients with FA and ALL. Our patient’s high-risk ALL appeared to respond to low-risk induction and minimal non-myelosuppressive post-induction chemotherapy. These observations suggest that minimal chemotherapy may be effective in these patients while awaiting SCT.