Efficacy of Low Dose Clofarabine in Refractory Precursor T- Acute Lymphoblastic Leukemia
JK is a 35-year-old male with precursor T-lymphoblastic leukemia diagnosed in 2001 with a bone marrow blast immunophenotype of CD2+CD7+CD3+ cells with aberrant expression of CD13 and negative staining for TdT and myeloperoxidase. His karyotypic analysis was indicative of a 4;11 translocation involving the MLL gene at 11q23. He was induced and underwent allogeneic stem cell transplantation (SCT) from his HLA-identical fraternal twin brother in April 2002. He was in remission with limited skin chronic graft-vs.-host disease until January 2003, when he relapsed and was treated with ICE chemotherapy followed by a donor lymphocyte infusion. He remained in remission until February 2005, when he developed nodular violacious skin lesions which on biopsy revealed T-cells consistent with his original leukemia. Full restaging including bone marrow biopsy and cerebrospinal fluid analysis were negative, indicating an isolated skin recurrence. Re-induction therapy was initiated with cyclophosphamide and gemcitabine but was complicated by significant myelosuppression and renal insufficiency. He received a brief course of systemic retinoid therapy with bexarotene and spot electron beam irradiation for symptomatic improvement of nodular disease on his face with rapid recurrence at the completion of radiation. He then was treated with nelarabine in February 2006 and responded but developed worsening renal insufficiency.\nHe quickly developed recurrent nodular tumors over his brow, around his right ear, on his chest, and on his back and chest []. On restaging in October 2006, the patient had no evidence of lymphadenopathy or involvement of liver or spleen by CT scan. A bone marrow biopsy revealed relapse of known precursor-T lymphoblastic leukemia involving 40 percent of the marrow. The cells were CD2+ CD7+ CD34+ HLA-DR+ CD3-. Flow cytometry of the blood was negative for blasts with only occasional reactive lymphocytes. At that time, his leukocyte count was 2.0 with 64 percent neutrophils and 35 percent lymphocytes, the hematocrit was 24.5 and platelets were 52 x 10³/dl. He initiated therapy with clofarabine at 10 mg/m2 weekly for three consecutive weeks every 28 days. Treatment schedule and toxicities are shown in Table 1. There was no hepatic toxicity, and only mild fluctuations of the creatinine were noted. Treatment was held on the third week of the first two cycles due to neutropenia.\nAfter two cycles of clofarabine, the patient’s lesions regressed significantly as shown in . Cycle 3 was delayed due to a hospitalization for herpetic esophagitis, which resolved with acyclovir therapy. He remains on weekly low-dose clofarabine with ongoing response after three months. His platelet count has been stable at 99,000/mm³. An unrelated donor has been identified, and the patient will undergo a second allogeneic stem cell transplant.