In each of these studies, common toxicities were nausea and liver enzyme abnormalities, which necessitated interruption and/or dose reduction of imatinib.[13,14] (Refer to the PDQ summary on Nausea and Vomiting for more information.) Subsequent allogeneic transplant does not appear to be adversely affected by the addition of imatinib to the treatment regimen.
Imatinib is generally incorporated into the treatment of patients with Ph1-positive ALL because of the responses observed in monotherapy trials. If a suitable donor is available, allogeneic bone marrow transplantation should be considered because remissions are generally short with conventional ALL chemotherapy clinical trials.
Since myelosuppression is an anticipated consequence of both leukemia and its treatment with chemotherapy, patients must be closely monitored during remission induction treatment. Facilities must be available for hematological support and for the treatment of infectious complications.
Supportive care during remission induction treatment should routinely include red blood cell and platelet transfusions, when appropriate.[19,20]
Evidence (Supportive care):
- Randomized clinical trials have shown similar outcomes for patients who received prophylactic platelet transfusions at a level of 10,000/mm3 rather than at a level of 20,000/mm3.
- The incidence of platelet alloimmunization was similar among groups randomly assigned to receive one of the following from random donors:
- Pooled platelet concentrates.
- Filtered, pooled platelet concentrates.
- Ultraviolet B-irradiated, pooled platelet concentrates.
- Filtered platelets obtained by apheresis.
Empiric broad-spectrum antimicrobial therapy is an absolute necessity for febrile patients who are profoundly neutropenic.[23,24] Careful instruction in personal hygiene and dental care and in recognizing early signs of infection are appropriate for all patients. Elaborate isolation facilities, including filtered air, sterile food, and gut flora sterilization, are not routinely indicated but may benefit transplant patients.[25,26]
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. Prophylactic oral antibiotics may be appropriate in patients with expected prolonged, profound granulocytopenia (<100/mm3 for 2 weeks), though further studies are necessary. Serial surveillance cultures may be helpful in detecting the presence or acquisition of resistant organisms in these patients.
As suggested in a CALGB study (CLB-9111), the use of myeloid growth factors during remission-induction therapy appears to decrease the time to hematopoietic reconstitution.[29,30]
CNS prophylaxis therapy
The early institution of CNS prophylaxis is critical to achieve control of sanctuary disease.
Special Considerations for B-Cell and T-Cell Adult ALL
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, including those previously used in CLB-9251 (NCT00002494), that are similar to those used in aggressive non-Hodgkin lymphoma have shown high response rates and cure rates (75% CR; 40% failure-free survival).[31,32,33] Similarly, T-cell ALL, including lymphoblastic lymphoma, has shown high cure rates when treated with cyclophosphamide-containing regimens.