Treating Acute Lymphocytic Leukemia in the Older Adult: the Moffitt Cancer Center Experience

Acute Lymphocytic Leukemia (ALL) is a heterogeneous and devastating disease in patients of all ages. However, there are prognostic indicators which are associated with worse outcomes including the presence of the Philadelphia (Ph) chromosome and age greater than 60. The percentage of ALL patients with Ph-positive disease increases with age. Relapse rates are much higher in Ph-positive ALL and five year survival rates are <10% in adults. Allogeneic hematopoetic stem cell transplant is necessary for a durable remission in this population, but this intervention introduces treatment related risks, especially in the senior population. Tyrosine kinase inhibitors (TKI) used in combination with standard chemotherapy or as single agents have demonstrated improved remission durations and disease-free survivals in adults. TKIs are well tolerated when used with intensive chemotherapy. HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine) has been shown to be an effective regimen in the treatment of adults with ALL, but in patients ≥60 years old, induction mortality has been reported to be 15%. Due to the lack of many efficacious induction regimens for ALL, this regimen is used in older adults with good performance status and vital organ status. Here we present our experience at Moffitt Cancer Center (MCC) in treating older adults with ALL.

Using the MCC Total Cancer Care database, patients were identified who were diagnosed and treated with ALL at MCC. Patient charts were reviewed individually, and all patients who were age 60 and above were included in this analysis. Hyper-CVAD was administered as originally described at M.D. Anderson Cancer Center (Kantarjian 2000). The remaining patients were treated with regimens including the Larson protocol, CALGB study 8801 regimen, ECOG 2993 and vincristine/glucocorticoid combinations. Ph-positive patients were treated with the addition of a TKI. Descriptive data were reported, t-test was used to compare continuous variables while chi square test was used for categorical variables. Kaplan Meier curves were used for OS and relapse free survival (RFS). Long rank test was used to compare survival times between groups. Cox regression analysis was used for multivariable analysis. All analyses were conducted using SPSS version 19.0 and Microsoft Excel 2010.

Between 1/1/2004 and 6/30/2011, a total of 41 patients (age 60 or greater) were treated at MCC for ALL. Fifty-six percent of these patients were male, 44% were female. The majority of patients were Caucasian (81%), 2% were African American and 17% were classified as other. Thirty-nine were diagnosed with precursor B-cell ALL (excluding Burkitts Leukemia) and 2 had the T-cell subtype. Nine of the patients were found to have Ph-positive disease and 30 had Ph-negative disease. Two patients had an unknown Ph chromosome status. ECOG performance status was 0–1 in 78% of the treated patients. Other leukemia prognostic indicators were evaluated demonstrating five percent with known CNS involvement, 10% with lymphadenopathy and 15% of patients with splenomegaly at the time of diagnosis. There were no differences in observed outcomes based on these demographics.

Sixty-three percent of patients were treated with HyperCVAD based chemotherapy frontline. All 9 patients with Ph-positive disease received a tyrosine kinase inhibitor. Seven of these patients were treated with imatinib and 2 received dasatinib.

Our review demonstrated a median OS for all patients over the age of 60 treated with any therapy was 24 months (95% CI 15–33). The OS for patients treated with HyperCVAD was 23 months (95% CI 14.9–31.1) as compared to 24 (95% CI 14.8–33.2) in those treated with other regimens (p=0.299)(fig 1). OS was 24 months (95% CI 14.8–33.2) in Ph-positive patients who were treated with a TKI as compared to 23 months (95% CI 12.7–33.3) in Ph-negative patients who were treated with standard chemotherapy (p=0.95). Two patients were able to proceed to allogeneic hematopoetic stem cell transplant.

Figure 1

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Figure 1

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In our experience prognosis remains poor in older adults with ALL. There was no statistical significant difference observed in median OS based on the type of chemotherapy regimen used in this population. Outcomes do appear improved in older adults with Ph-positive ALL with the use of TKIs.

No relevant conflicts of interest to declare.