A Comparison of Two Induction Regimens for Older Patients with Acute Lymphoblastic Leukemia: Daunorubicin, Vincristine and Prednisone (DVP) is Worth Considering

The prognosis for older patients with newly-diagnosed acute lymphoblastic leukemia (ALL) is generally poor, although a limited number of studies suggest that these patients can experience favorable outcomes when treated with standard intensive chemotherapy. However, a comparative analysis of curative regimens has not been performed to date. Here, we describe outcomes in patients diagnosed with ALL at age ≥60 who received induction at our institution with either hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine (hyperCVAD) or daunorubicin, vincristine and prednisone (DVP).

Of the 44 patients diagnosed with ALL at age ≥60 who were treated at the University of Pennsylvania between July 2003 and June 2009, 38 received either hyperCVAD (n=24) or DVP (n=14). Induction regimens were chosen at the discretion of the treating physician. Patients in the hyperCVAD group received a median of 6 (range 1–8) cycles. Patients in the DVP group received a full course of induction therapy following the regimen used in the ECOG 2993/UKALL XII protocol with a majority receiving second induction, intensification and consolidation therapy. L-asparaginase was omitted from DVP therapy for all but 2 patients. Assessment for response or relapse was performed primarily via bone marrow biopsy as clinically indicated. If lost to follow-up, patients with previously documented remission were considered to remain in remission through the time of their last normal complete blood count. All deaths were confirmed through the Social Security Death Index. Categorical data was analyzed via the Fisher's exact test and survival times were calculated via Kaplan-Meier plots.

Table 1 reports baseline characteristics at diagnosis for patients in the hyperCVAD and DVP groups. Tables 2 and 3 report the rates of complete response (CR) and relapse as well as median progression free survival (PFS) and median overall survival (OS) for the two treatment groups. The median length of follow-up was 12.5 months for the hyperCVAD group (range 3–70) and 24 months for the DVP group (range 4–136). Five-year survival was 4% for hyperCVAD patients and 36% for DVP patients (p=0.019). No deaths occurred within the initial 2 months of treatment in either group. Maintenance chemotherapy was received by 50% of hyperCVAD patients and 70% of DVP patients. Of the Ph(+) patients in who received hyperCVAD, 75% received a tyrosine kinase inhibitor (TKI) with induction therapy and 50% with maintenance therapy. Of the Ph(+) patients in who received DVP, 29% received a TKI with induction therapy and 83% with maintenance therapy. All Ph(+) patients who experienced OS greater than the median OS for Ph(+) patients within their respective treatment groups received a TKI. These results did not achieve statistical significance unless otherwise noted.

Older patients diagnosed with ALL can enjoy prolonged survival when treated with intensive induction regimens. While this has been previously described in patients receiving hyperCVAD, our analysis indicates that patients diagnosed with ALL at age ≥60 treated with DVP may experience longer OS compared to those treated with hyperCVAD despite an apparent lower rate of complete response and similar rate of relapse. Additionally, Ph(+) patients within this population may experience similar or better outcomes than Ph(-) patients when treated with either regimen, possibly related to the use of TKIs. Prospective trials are warranted to more rigorously evaluate these induction therapies in the older ALL population.

No relevant conflicts of interest to declare.