Treatment for Recurrent Adult ALL

Standard Treatment Options for Recurrent Adult ALL

Standard treatment options for recurrent adult ALL include the following:

1. Reinduction chemotherapy followed by allogeneic bone marrow transplantation (alloBMT).
2. Palliative radiation therapy (for patients with symptomatic recurrence).
3. Dasatinib (for patients with Philadelphia chromosome [Ph1]-positive ALL).

Reinduction chemotherapy

Patients with ALL who experience a relapse following chemotherapy and maintenance therapy are unlikely to be cured by further chemotherapy alone. These patients should be considered for reinduction chemotherapy followed by alloBMT.

Palliative radiation therapy

Low-dose palliative radiation therapy may be considered in patients with symptomatic recurrence either within or outside the central nervous system.[1]

Dasatinib

Patients with Ph1-positive ALL will often be taking imatinib at the time of relapse and thus will have imatinib-resistant disease. Dasatinib, a novel tyrosine kinase inhibitor with efficacy against several different imatinib-resistant BCR-ABL mutations, has been approved for use in Ph1-positive ALL patients who are resistant to or intolerant of imatinib. The approval was based on a series of trials involving patients with chronic myelogenous leukemia, one of which included small numbers of patients with lymphoid blast crisis or Ph1-positive ALL.

Evidence (Dasatinib):

1. In one study, ten patients were treated with dose-escalated dasatinib.[2] Seven of these patients had a complete hematologic response (<5% marrow blasts with normal peripheral blood cell counts), three of whom had a complete cytogenetic response.
   • The common toxicities were reversible myelosuppression (89%) and pleural effusions (21%).
   • Virtually all of these patients relapsed within 6 months of the start of treatment with dasatinib.

Treatment Options Under Clinical Evaluation for Recurrent Adult ALL

Patients for whom an HLA-matched donor is not available are excellent candidates for enrollment in clinical trials that are studying the following:[3,4,5,6,7,8,9]

1. Autologous transplantation.
2. Immunomodulation.
3. Novel chemotherapeutic or biological agents.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult acute lymphoblastic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

1. Gray JR, Wallner KE: Reversal of cranial nerve dysfunction with radiation therapy in adults with lymphoma and leukemia. Int J Radiat Oncol Biol Phys 19 (2): 439-44, 1990.
2. Talpaz M, Shah NP, Kantarjian H, et al.: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354 (24): 2531-41, 2006.
3. Herzig RH, Bortin MM, Barrett AJ, et al.: Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission. Lancet 1 (8536): 786-9, 1987.
4. Thomas ED, Sanders JE, Flournoy N, et al.: Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up. Blood 62 (5): 1139-41, 1983.
5. Barrett AJ, Horowitz MM, Gale RP, et al.: Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival. Blood 74 (2): 862-71, 1989.
6. Dinsmore R, Kirkpatrick D, Flomenberg N, et al.: Allogeneic bone marrow transplantation for patients with acute lymphoblastic leukemia. Blood 62 (2): 381-8, 1983.
7. Sallan SE, Niemeyer CM, Billett AL, et al.: Autologous bone marrow transplantation for acute lymphoblastic leukemia. J Clin Oncol 7 (11): 1594-601, 1989.
8. Paciucci PA, Keaveney C, Cuttner J, et al.: Mitoxantrone, vincristine, and prednisone in adults with relapsed or primarily refractory acute lymphocytic leukemia and terminal deoxynucleotidyl transferase positive blastic phase chronic myelocytic leukemia. Cancer Res 47 (19): 5234-7, 1987.
9. Biggs JC, Horowitz MM, Gale RP, et al.: Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 80 (4): 1090-3, 1992.