Therapy-Related Acute Lymphoblastic Leukemia (t-ALL).

Introduction: Myelodysplasia and Acute Myeloid Leukemia are recognized and well characterized complications of cancer therapy. Much less is known about t-ALL, but an increasing number of cases are being reported.

Materials and Methods: We conducted a MEDLINE search to identify patients with ALL diagnosed after exposure to chemotherapy and/or radiotherapy. Data extracted included: latency period, radiation and type of chemotherapy drug exposure, phenotype, cytogenetics and survival.

Results: 74 patients were identified with a median age at the time of t-ALL of 33 years, (range 2 to 90; 16 cases age ≤ 10 and 9 cases age ≥60). History of a prior malignancy, including solid tumors in 45 (sarcomas 12, breast cancer 11, others 22) and hematological malignancies in 25 (Hodgkin’s lymphoma 17, others 8), was documeted in all patients with the exception of 4, who received chemotherapy or radiation for a non-malignant disorder. Exposure to radiotherapy was documented in 65% of patients (4 cases had exposure only to radiotherapy), 64% had recieved topoisomerase II inhibitors and 84% other chemotherapy drugs. Median time to t-ALL was 38 months. Follow up data was available in 56/74 (75.6%), 20 were reported alive (27%), 3 to 132 months from t-ALL diagnosis. Twelve patients received stem cell transplants, 7 of them were survivors (8 to 79 months). Based on phenotype and/or cytogenetics, 5 subsets of patients were identified. Group A: 32 patients (43%) with 11q23 translocations and/or MLL rearrangements: 23 of these patients (72%) presented with pro-B cell phenotype (CD19+, CD10−)(2 pre-B cell, 2 T cell, 5 unknown); 90% had history of exposure to topoisomerase II inhibitors; median time to t-ALL was 21 months in Group A, significanlty shorter (p<.0001) when compared to all other patients (median 60 months). Median overall survival was 8 months, 5 year survival 27%. Group B: 11 patients (14.8%), with L3/Burkitt’s leukemia; all with t(8;14), t(8;22) or t(2;8) abnormalities. None of them are long term survivors. Group C: 4 patients with t(9;22) (5.4%). Group D: 4 patients with T cell phenotype (5.4%). Group E: the remaining 23 patients (31%) with primarily a pre-B cell phenotype (CD19+, CD10+) with normal (21.7%), complex (21.7%) or unknown cytogenetics (56%). Of the 18 patients who received induction therapy in Group E, 9 (50%) are survivors (median 60 months from diagnosis).

Conclusions: Various subsets of t-ALL can be recognized, resembling the pattern seen in patients with de novo ALL. However, high-risk subtypes such as 11q23/MLL + cases are overrepresented. Patients with t-ALL not identified by 11q23 or t(9;22) abnormalities, L3/Burkitt’s or T cell phenotype (Group E) appear to have a better prognosis: survival at 5 years 45% compared to 24% for all other patients.