Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia.

Abstract

One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD-CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches.

Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period

“…The WBC count at diagnosis has consistently been found to be associated with outcome. 29 WBC is simply a reflection of tumor burden suggesting that with greater tumor burden there is an increased chance for the emergence of a drug-resistant clone. It is also just as possible that the link between a high WBC and chemotherapy resistance reflects an inability of the leukemic cell to arrest and undergo apoptosis in response to chemotherapy, or any of a number of other abnormalities.…”

“…According to most reports, 68 to 88% of adult ALL patients achieve CR after intensive chemotherapy. 2,3,7,[27][28][29] Median CR duration ranged from 20 to 32 months with longterm survival at about 30%. However, effects of selection on treatment results have been highlighted by most studies.…”

Alpha-interferon improves survival and remission duration in P-190BCR-ABL positive adult acute lymphoblastic leukemia

“…[34][35][36][37][38][39] Since CR rates over 60% can be achieved with intensified as well as standard induction regimens, the problem is not so much how to obtain CR but how to maintain remission. Intensified consolidation regimens based on chemotherapy or on chemotherapy and autologous stem cell transplantation are probably useful in reducing the tumor load, although the long-term results still appear unsatisfactory with high percentages of early relapses.…”

A phase I trial of a single high dose of idarubicin combined with high-dose cytarabine as induction therapy in relapsed or refractory adult patients with acute lymphoblastic leukemia

“…[1][2][3][4][5][6][7][8][9][10][11] There is a significant relapse rate, however, and only 20-30% of all patients will be cured of their disease. [1][2][3][4][5][6][7][8][9][10][11] Therefore the majority of adults with ALL will require therapy for relapsed or refractory disease.…”