Current Clinical Trials

Standard treatment options for remission induction therapy:

Most current induction regimens for patients with adult acute lymphoblastic leukemia (ALL) include prednisone, vincristine, and an anthracycline. Some regimens, including a Cancer and Leukemia Group B study (CALGB-8811), also add other drugs, such as asparaginase or cyclophosphamide. Current multiagent induction regimens result in complete response rates that range from 60% to 90%.[1-3]

Imatinib mesylate is often incorporated into the therapeutic plan for patients with Ph1-positive ALL. Several studies have suggested that the addition of imatinib results in complete response rates, event-free survival rates, and overall survival rates that are higher than those in historical controls. In each of these studies, common toxicities were nausea and liver enzyme abnormalities necessitating interruption and/or dose reduction of imatinib. (For more information on nausea, refer to the PDQ summary on Nausea and Vomiting.) Subsequent allogeneic transplant does not appear to be adversely affected by the addition of imatinib to the treatment regimen. At the present time, no conclusions can be drawn from these studies regarding which imatinib dose or schedule should be used.[4-6]

Two additional subtypes of adult ALL require special consideration. B-cell ALL [which expresses surface immunoglobulin and cytogenetic abnormalities such as t(8;14), t(2;8), and t(8;22)] is not usually cured with typical ALL regimens. Aggressive brief duration high-intensity regimens, as evidenced in the Cancer and Leukemia Group B study (CALGB-9251), similar to those used in aggressive non-Hodgkin lymphoma have shown high response rates and cure rates (75% complete remission; 40% failure-free survival).[7,8] T-cell ALL, including lymphoblastic lymphoma, similarly has shown high cure rates when treated with cyclophosphamide-containing regimens.[3] Whenever possible, such patients should be entered in clinical trials designed to improve the outcomes in these subsets. (Refer to the B cell (Burkitt) lymphoma and T cell (lymphoblastic) lymphoma sections in the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.)

Since myelosuppression is an anticipated consequence of both the leukemia and its treatment with chemotherapy, patients must be closely monitored during remission induction treatment. Facilities must be available for hematological support as well as for the treatment of infectious complications.

Supportive care during remission induction treatment should routinely include red blood cell and platelet transfusions when appropriate.[9,10] Randomized trials have shown similar outcomes for patients who received prophylactic platelet transfusions at a level of 10,000/mm³ rather than 20,000/mm³.[11] The incidence of platelet alloimmunization was similar among groups randomly assigned to receive pooled platelet concentrates from random donors; filtered, pooled platelet concentrates from random donors; ultraviolet B-irradiated, pooled platelet concentrates from random donors; or filtered platelets obtained by apheresis from single random donors.[12] Empiric broad spectrum antimicrobial therapy is an absolute necessity for febrile patients who are profoundly neutropenic.[13,14] Careful instruction in personal hygiene, dental care, and recognition of early signs of infection are appropriate in all patients. Elaborate isolation facilities, including filtered air, sterile food, and gut flora sterilization are not routinely indicated but may benefit transplant patients.[15,16] Rapid marrow ablation with consequent earlier marrow regeneration decreases morbidity and mortality. White blood cell transfusions can be beneficial in selected patients with aplastic marrow and serious infections that are not responding to antibiotics.[17] Prophylactic oral antibiotics may be appropriate in patients with expected prolonged, profound granulocytopenia (<100/mm³ for 2 weeks), though further studies are necessary.[18] To detect the presence or acquisition of resistant organisms, serial surveillance cultures may be helpful in such patients. As evidenced in a Cancer and Leukemia Group B study (CALGB-9111), the use of myeloid growth factors during remission induction therapy appears to decrease the time to hematopoietic reconstitution.[19,20]

Treatment options for remission induction therapy under clinical evaluation:

• Clinical trials are ongoing, and patients should be considered for these studies.

Standard treatment options for central nervous system (CNS) prophylaxis:

The early institution of CNS prophylaxis is critical to achieve control of sanctuary disease.

1. Cranial radiation therapy plus intrathecal (IT) methotrexate.
2. High-dose systemic methotrexate and IT methotrexate without cranial therapy radiation.
3. IT chemotherapy alone.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with untreated 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. Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988.  [PUBMED Abstract]
   
   
2. Linker CA, Levitt LJ, O'Donnell M, et al.: Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 78 (11): 2814-22, 1991.  [PUBMED Abstract]
   
   
3. Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85 (8): 2025-37, 1995.  [PUBMED Abstract]
   
   
4. Thomas DA, Faderl S, Cortes J, et al.: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103 (12): 4396-407, 2004.  [PUBMED Abstract]
   
   
5. Yanada M, Takeuchi J, Sugiura I, et al.: High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 24 (3): 460-6, 2006.  [PUBMED Abstract]
   
   
6. Wassmann B, Pfeifer H, Goekbuget N, et al.: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 108 (5): 1469-77, 2006.  [PUBMED Abstract]
   
   
7. Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996.  [PUBMED Abstract]
   
   
8. Lee EJ, Petroni GR, Schiffer CA, et al.: Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 19 (20): 4014-22, 2001.  [PUBMED Abstract]
   
   
9. Slichter SJ: Controversies in platelet transfusion therapy. Annu Rev Med 31: 509-40, 1980.  [PUBMED Abstract]
   
   
10. Murphy MF, Metcalfe P, Thomas H, et al.: Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62 (3): 529-34, 1986.  [PUBMED Abstract]
    
    
11. Rebulla P, Finazzi G, Marangoni F, et al.: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. N Engl J Med 337 (26): 1870-5, 1997.  [PUBMED Abstract]
    
    
12. Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 337 (26): 1861-9, 1997.  [PUBMED Abstract]
    
    
13. Hughes WT, Armstrong D, Bodey GP, et al.: From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 161 (3): 381-96, 1990.  [PUBMED Abstract]
    
    
14. Rubin M, Hathorn JW, Pizzo PA: Controversies in the management of febrile neutropenic cancer patients. Cancer Invest 6 (2): 167-84, 1988.  [PUBMED Abstract]
    
    
15. Armstrong D: Symposium on infectious complications of neoplastic disease (Part II). Protected environments are discomforting and expensive and do not offer meaningful protection. Am J Med 76 (4): 685-9, 1984.  [PUBMED Abstract]
    
    
16. Sherertz RJ, Belani A, Kramer BS, et al.: Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients. Am J Med 83 (4): 709-18, 1987.  [PUBMED Abstract]
    
    
17. Schiffer CA: Granulocyte transfusions: an overlooked therapeutic modality. Transfus Med Rev 4 (1): 2-7, 1990.  [PUBMED Abstract]
    
    
18. Wade JC, Schimpff SC, Hargadon MT, et al.: A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia. N Engl J Med 304 (18): 1057-62, 1981.  [PUBMED Abstract]
    
    
19. Scherrer R, Geissler K, Kyrle PA, et al.: Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL). Ann Hematol 66 (6): 283-9, 1993.  [PUBMED Abstract]
    
    
20. Larson RA, Dodge RK, Linker CA, et al.: A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood 92 (5): 1556-64, 1998.  [PUBMED Abstract]
    
    

Back to Top

< Previous Section  |  Next Section >