A phase II study of sequential combination chemotherapy with cyclophosphamide (ctx), prednisone, and 2-chlorodeoxyadenosine (2-CDA) in previously untreated patients with chronic lymphocytic leukemia (CLL)

Ayalew Tefferi, Craig B. Reeder, Susan M. Geyer, Crisitine Allmer, Chin Y. Li, Ralph Levitt, John C. Michalak, Ferdinand Addo, James E. Krook, Thomas E. Witzig, Paul L. Schaefer, James A. Maillard

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Abstract

Background: In an earlier study of previously untreated patients with CLL, we had used a concomitant combination of chlorambucil (CLB) and 2-CdA and reported overall (OR) and complete (CR) remission rates of 80 and 20%, respectively. After a median followup period of 5 years, more than 80% of the responders (including all of those with CR) have now relapsed. Methods: In the current phase II study of previously untreated patients with CLL, we used a sequential combination of 6 cycles of intravenous (IV) CTX (1 gm/m2) + oral prednisone (100 mg/m2/day x 5 days) followed by 2-6 cycles of 2-CdA (5 mg/m2/day x 5 days). Response designations were according to currently established criteria. Results: Twenty-seven eligible patients (median age, 64 years) were enrolled into the study (Rai high-risk, 45%; CD38+, 40%). The OR and CR rates were 96 and 33%, respectively. Best response was achieved only after the institution of 2-CdA in 52% of the patients. Despite the phenotypic detection of minimal residual disease (MRD) in 4 of 9 CR cases, progression-free survival (PFS) was significantly better in CR than in partial remission (PR). After a median follow-up time of 29 months, 35% of the responders have relapsed. Neither CR achievement nor PFS was affected by the status of CD38 expression by CLL cells. Severe neutropenia or thrombocytopenia occurred in 37% and 0% of the patients, respectively. Conclusion: Sequential combination chemotherapy with standard doses of 2-CdA and CTX is well-tolerated in previously untreated patients with CLL. The OR and CR rates observed were superior to those seen in a historical cohort treated with a concomitant schedule and similar to reported rates associated with CTX and fludarabine combinations. However, the high early relapse rate and frequent phenotypic detection of MRD in patients with CR make it unlikely that the particular combination schedule will be effectively better. Our experience from 2 consecutive treatment trials does not suggest that a combination of PNA and alkylator-based chemotherapy will substantially alter the natural history of CLL.

Original languageEnglish (US)
Pages (from-to)295b
JournalBlood
Volume96
Issue number11 PART II
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Tefferi, A., Reeder, C. B., Geyer, S. M., Allmer, C., Li, C. Y., Levitt, R., Michalak, J. C., Addo, F., Krook, J. E., Witzig, T. E., Schaefer, P. L., & Maillard, J. A. (2000). A phase II study of sequential combination chemotherapy with cyclophosphamide (ctx), prednisone, and 2-chlorodeoxyadenosine (2-CDA) in previously untreated patients with chronic lymphocytic leukemia (CLL). Blood, 96(11 PART II), 295b.