Relapsed ALL

Relapse is the recurrence of leukemic cells at any site after remission has been achieved. Relapse is a major complication for 15% to 20% of patients with ALL.

Current research suggests that this is the result of residual leukemic cells at diagnosis.

Thus the importance ofMRD. Bone marrow relapse is the principal form of treatment failure in patients with ALL. Extramedullary sites of relapse include the CNS

and the testicles. Extramedullary relapse while once common, has decreased to 5% or less because of effective prophylaxis. Site of relapse and the length of the first remission are important predictors of second remission and OS. Marrow relapses occurring less than 18 to 24 months into first remission are associated with a poor survival, while longer periods of remission, greater than 36 months, have a much higher chance

of survival. Treatment strategies for relapsed ALL include chemotherapy or allogeneic hematopoietic stem cell transplant (allo-HSCT). Even though patients undergoing allo-HSCT are less likely to relapse, treatment-related toxicity leads to a higher incidence of morbidity and mortality as compared to chemotherapy alone.6 Clofarabine, a next-generation deoxyadenosine analog, has shown considerable activity in children and adults with refractory acute leukemias. Of interest, this is the only anticancer drug

to receive primary indication for use in pediatrics in the last 10 years.

Table 95-9 Representative Chemotherapy Regimens for Pediatric ALL

Induction (1 month)

Intrathecal cytarabine on day 0

Prednisone 40 mg/m /day or dexamethasone 6 mg/m /day orally for 28 days 2

Vincristine 1.5 mg/m /dose (max 2 mg) IV weekly for 4 doses

22 Pegaspargase 2,500 units/m /dose IM for 1 dose or asparaginase 6,000 units/m /dose IM Mon, Wed, and

Fri for 6 doses Intrathecal methotrexate weekly for 2-4 doses Consolidation (1 month)

Mercaptopurine 50-75 mg/m /dose orally at bedtime for 28 days Vincristine 1.5 mg/m /dose (max 2 mg) IV on day 0 Intrathecal methotrexate weekly for 1-3 doses

Patients with CNS or testicular disease may receive radiation Interim Maintenance (1 or 2 cycles) (2 months)

Methotrexate 20 mg/m /dose orally at bedtime weekly 2

Mercaptopurine 75 mg/m /dose orally daily on days 0-49 2

Vincristine 1.5 mg/m /dose (max 2 mg) IV on days 0 and 28 2

Dexamethasone 6 mg/m /day orally on days 0-4 and 28-32

Delayed Intensification (1 or 2 cycles) (2 months) 2

Dexamethasone 10 mg/m /day orally on days 0-6 and 14-20 2

Vincristine 1.5 mg/m /dose (max 2 mg) IV weekly for 3 doses 2

Pegaspargase 2,500 units/m /dose IM for 1 dose 2

Doxorubicin 25 mg/m /dose IV on days 0, 7, and 14

Cyclophosphamide 1,000 mg/m /dose IV on day 28 2

Thioguanine 60 mg/m /dose orally at bedtime on days 28-41 Cytarabine 75 mg/m /dose SC or IV on days 28-31 and 35-38 Intrathecal methotrexate on days 0 and 28

Consolidation Option (2-3-week intervals for 6 courses on weeks 5-24)

Mercaptopurine 50 mg/m /dose orally at bedtime 2

Prednisone 40 mg/m /day for 7 days on weeks 8 and 17 2

Vincristine 1.5 mg/m /dose (max 2 mg) IV on the first day of weeks 8, 9, 17, and 18 22

Methotrexate 200 mg/m /dose IV + 800 mg/m /dose over 24 hours on day 1 of weeks 7, 10, 13, 16, 19, and 22

Intrathecal methotrexate on weeks 5, 6, 9, 12, 15, and 18

Late Intensification (weeks 25-52)

22 Methotrexate 20 mg/m /dose IM weekly or 25 mg/m /dose orally every 6 hours for 4 doses every other week

Mercaptopurine 75 mg/m /dose orally at bedtime 2

Prednisone 40 mg/m /day orally for 7 days on weeks 25 and 41 2

Vincristine 1.4 mg/m w/dose (max 2 mg) IV on the first day of weeks 25, 26, 41, and 42 Intrathecal methotrexate on day 1 of weeks 25, 33, 41, and 49 Maintenance (12-week cycles)

Methotrexate 20 mg/m /dose orally at bedtime or IM weekly with dose escalation as tolerated

Mercaptopurine 75 mg/m /dose orally at bedtime on days 0-83 2

Vincristine 1.5 mg/m /dose (max 2 mg) IV on days 0, 28, and 56 2

Dexamethasone 6 mg/m /day orally on days 0-4, 28-32, and 56-60 Intrathecal methotrexate on day 0

IM, intramuscular; SC, subcutaneous.

Adapted from Leather HL, Bickert B. Acute Leukemias. In: DiPiro JT, Talbert RL, Yee GC, et al., (eds.) Pharmacotherapy: A Pathophysiologic Approach, 6th ed. New York: McGraw-Hill; 2005: 2458-2511.

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