Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia

2000 ◽  
Vol 18 (3) ◽  
pp. 547-547 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Susan O’Brien ◽  
Terry L. Smith ◽  
Jorge Cortes ◽  
Francis J. Giles ◽  
...  
Keyword(s):  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Disease ◽  
Adult Acute Lymphocytic Leukemia ◽  
Intensive Regimen

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 × 109/L was found in 26%, Philadelphia chromosome–positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

Outcome with Hyper-CVAD/MTX-Ara-C, a Dose-Intensive Regimen, in Acute Lymphocytic Leukemia and Highly Aggressive Lymphoma: A Preliminary Study in a Single Center in China.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4529-4529
Author(s):  
Ting Niu ◽  
Ting Liu ◽  
Bing Xiang ◽  
Hong Chang ◽  
Yong-qian Jia ◽  
...  
Keyword(s):  
Side Effects ◽  
Acute Lymphocytic Leukemia ◽  
Burkitt’S Lymphoma ◽  
Lymphocytic Leukemia ◽  
Burkitt's Lymphoma ◽  
Aggressive Lymphoma ◽  
Single Center ◽  
Cell Disease ◽  
Relapsed Disease ◽  
Intensive Regimen

Abstract BACKGROUND: Although the safety and efficacy of the Hyper-CVAD/MTX-Ara-C regimen in hematologic malignancies has been well established by the large clinical trials developed at the University of Texas M. D. Anderson Cancer Center, the outcome with this regimen in patients in China has not been determined. The objective of this study was to evaluate the efficacy and potential toxicity of this regimen in acute lymphocytic leukemia (ALL) and highly aggressive non-Hodgkin lymphoma (NHL) in a single center in China. PATIENTS AND METHODS: Between September 2004 and July 2006,36 patients with ALL or highly aggressive lymphoma were treated with the Hyper-CVAD/MTX-Ara-C regimen at our institution. Median age was 35 years (range 14 to 60 years), and 23 patients (64%) were male. All patients are comprised of 19 previously untreated cases and 17 refractory/relapsed ones. Among the 28 patients with ALL, B-cell disease was present in 82%, T-cell disease in 18%, and Ph-positive ALL was present in 18%, refractory/relapsed disease in 46%. Among the 8 patients with highly aggressive NHL, lymphoblastic lymphoma was present in 63%, Burkitt’s lymphoma was in 37% and refractory/relapsed disease in 50%. CNS involvement was present in 8% at diagnosis. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and aggressive supportive care with granulocyte colony-stimulating factor, transfusion and antibiotic prophylaxis therapy. Maintenance therapy according to cytogenetics and immunophenotype in partial patients included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: The median follow-up was 7 months (range 1+ to 23+ months). Of the previously untreated 19 patients, seventeen patients (89.47%) achieved complete remission (CR) and no patients died during induction therapy. Of the refractory/relapsed 17 patients, seven cases (41.48%) achieved CR. Remarkably, the CR rate of the patients with Ph-positive ALL was 60.00%(3/5), and Burkitt’s lymphoma 66.67%(2/3). The median finished courses during the dose-intensive phase were 5 (range 1 to 8), and the median time to delivery of all eight courses was 10 months. The estimated 5-year survival and 5-year CR rates were not concluded so far. The incidence of CNS relapse was low (5%). Myelosuppression-associated complications including documented infections, fever of unknown origin, hemorrhage were the more frequent side effects. Other significant side effects included neurotoxicity, renal and hepatic toxicities, fatigue, mucositis, nausea, vomiting, diarrhea, skin rashes, and G-CSF therapy-associated bone aches. CONCLUSION: The preliminary experience from our single center in China demonstrated that Hyper-CVAD/MTX-Ara-C, a dose-intensive regimen with much higher CR is superior to our previous regimens, even in poor-risk Ph-positive ALL, and highly aggressive lymphomas such as lymphoblastic and Burkitt’s lymphoma, and refractory/relapsed ALL/lymphoma. Our data also showed that this regimen is less toxic and well tolerated in patients. Due to the aggressive supportive care, the expense with this regimen is more expensive than conventional chemotherapy. Long-term treatment benefits, such as disease-free survival rates and severe side effects need further investigation in a well-designed, multiple-center study in China with more eligible patients entering onto the study.

scholarly journals Analysis of the BCR-ABL protein in Philadelphia chromosome-positive adult acute lymphocytic leukemia

Leukemia ◽  
1997 ◽  
Vol 11 (9) ◽  
pp. 1583-1587 ◽  
Author(s):  
AW Bseiso ◽  
HM Kantarjian ◽  
JQ Guo ◽  
J Cortes ◽  
M Talpaz ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Adult Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome Positive

Outcome with Hyper-CVAD/MTX-Ara-C, a Dose-Intensive Regimen, in Acute Lymphocytic Leukemia and Highly Aggressive Lymphoma in China.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4328-4328
Author(s):  
Ting Niu ◽  
Ting Liu ◽  
Bing Xiang ◽  
Hong Chang ◽  
Yong-qian Jia ◽  
...  
Keyword(s):  
Side Effects ◽  
Acute Lymphocytic Leukemia ◽  
Burkitt’S Lymphoma ◽  
Lymphocytic Leukemia ◽  
Burkitt's Lymphoma ◽  
Aggressive Lymphoma ◽  
Cell Disease ◽  
Long Term Treatment ◽  
Relapsed Disease ◽  
Intensive Regimen

Abstract Purpose: The objective of this study was to evaluate the efficacy and potential toxicity of the Hyper-CVAD/MTX-Ara-C regimen,a dose-intensive regimen, in the patients with acute lymphocytic leukemia (ALL) and highly aggressive non-Hodgkin lymphoma (NHL) in China. PATIENTS AND METHODS: Between June 2004 and June 2007, fifty-six patients with ALL or highly aggressive lymphoma were treated with the Hyper-CVAD/MTX-Ara-C regimen at our institution. Median age was 26 years (range 13 to 60 years), and 35 patients (62.50%) were male. All patients were comprised of 32 previously untreated cases and 24 refractory/relapsed ones. Among the 41 patients with ALL, B-cell disease was present in 82.93%, T-cell disease in 17.07%, and Ph-positive ALL was present in 14.63%, refractory/relapsed disease in 43.90%. Among the 15 patients with highly aggressive NHL, lymphoblastic lymphoma was present in 46.67%, Burkitt’s lymphoma was in 53.33% and refractory/relapsed disease in 40.00%. CNS involvement was present in 8% at diagnosis. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and aggressive supportive care with granulocyte colony-stimulating factor (G-CSF), transfusion and antibiotic prophylaxis therapy. Maintenance therapy based on cytogenetics and immunophenotypes in most of patients contained 2-year treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: The median follow-up time was 7 months (range 1+ to 37+ months). Of the previously untreated 31 patients, twenty-nine patients (93.55%) achieved complete remission (CR) and no patients died during induction therapy. Of the refractory /relapsed 24 patients, fourteen cases (58.33%) achieved CR. Remarkably, the CR rate of the patients with Burkitt’s lymphoma was 75.00% (6/8). The median courses finished during the dose-intensive phase were 4 (range 1 to 8), and the median time to delivery of all eight courses was 10 months. The estimated 3-year overall survival (OS) for the untreated and refractory/relapsed patients with ALL was 46.80% and 28.60%, respectively. Meanwhile, the estimated 2-year OS for the aggressive NHL patients was 84.00%. Compared with the patients with ALL who did not receive CR and get less than four courses of this regimen, the patients who did receive CR and get more than four courses of this dose-intensive regimen showed much better OS (p<0.05). The incidence of CNS relapse was low (5%). Myelosuppression-associated complications including documented infections, fever of unknown origin, hemorrhage were the more frequent side effects. Other significant side effects included neurotoxicity, renal and hepatic toxicities, fatigue, mucositis, nausea, vomiting, diarrhea, skin rashes, and G-CSF therapy-associated bone aches. CONCLUSION: The present outcome from our single center in China demonstrated that Hyper-CVAD/MTX-Ara-C, a dose-intensive regimen with much higher CR was superior to our previous regimens, even in patients with highly aggressive lymphoma such as lymphoblastic and Burkitt’s lymphoma, and in refractory/relapsed ALL/lymphoma ones. Our study also showed that this regimen was less toxic and well tolerated in most of treated patients in China. Long-term treatment benefits and severe side effects needed further investigation in a well-designed, multiple-center study in China with more eligible patients entering onto the study.

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

1990 ◽  
Vol 8 (6) ◽  
pp. 994-1004 ◽  
Author(s):  
H M Kantarjian ◽  
R S Walters ◽  
M J Keating ◽  
T L Smith ◽  
S O'Brien ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Lymphocytic Leukemia ◽  
Autologous Bone Marrow Transplantation ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Older Age ◽  
Leukemic Cells ◽  
High Dose ◽  
Long Term Outcome

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.

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