MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: the 8-year results of the intergroup trial.

1998 ◽  
Vol 16 (1) ◽  
pp. 19-26 ◽  
Author(s):  
J H Glick ◽  
M L Young ◽  
D Harrington ◽  
R L Schilsky ◽  
T Beck ◽  
...  
Keyword(s):  
Overall Survival ◽  
Relative Risk ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Myelogenous Leukemia ◽  
Life Threatening ◽  
Acute Myelogenous ◽  
First Relapse ◽  
Sequential Regimen

PURPOSE To compare the efficacy of sequential mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) followed by doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus the MOPP/ABV hybrid regimen in advanced-stage Hodgkin's disease. PATIENTS AND METHODS A total of 737 patients with previously untreated stages III2A, IIIB, IVA, or IVB Hodgkin's disease and patients in first relapse after radiotherapy were prospectively randomized to sequential MOPP-ABV or MOPP/ABV hybrid. Of 691 eligible patients, 344 received the sequential regimen and 347 received the hybrid. RESULTS The overall response rate was 95%, with complete responses (CRs) in 79%: 83% on the MOPP/ABV hybrid and 75% on the sequential MOPP-ABVD arm (P = .02). With a median follow-up time of 7.3 years, the 8-year failure-free survival (FFS) rates were 64% for MOPP/ABV hybrid and 54% far sequential MOPP-ABVD (P = .01; 0.69 relative risk of failure, comparing MOPP/ABV hybrid v MOPP-ABVD). The 8-year overall survival rate was significantly better for the MOPP/ABV hybrid (79%) as compared with sequential MOPP-ABVD (71%) (P = .02; relative risk, 0.65). MOPP/ABV hybrid had significantly more life-threatening or fatal neutropenia and pulmonary toxicity than the sequential MOPP-ABVD arm, which was associated with significantly greater thrombocytopenia. Nine cases of acute myelogenous leukemia or myelodysplasia were reported on the sequential regimen as compared with only one on the hybrid (P = .01). CONCLUSION MOPP/ABV hybrid chemotherapy was significantly more effective than sequential MOPP-ABVD. FFS and overall survival were significantly improved on the hybrid arm, which was also associated with a lower incidence of acute leukemia or myelodysplasia.

Randomized Comparison of ABVD and MOPP/ABV Hybrid for the Treatment of Advanced Hodgkin’s Disease: Report of an Intergroup Trial

2003 ◽  
Vol 21 (4) ◽  
pp. 607-614 ◽  
Author(s):  
David B. Duggan ◽  
Gina R. Petroni ◽  
Jeffrey L. Johnson ◽  
John H. Glick ◽  
Richard I. Fisher ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Hematologic Toxicity ◽  
Standard Regimen ◽  
Life Threatening ◽  
P 16 ◽  
Clinically Significant ◽  
Advanced Hodgkin’S Disease

Purpose: In a series of trials, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) have been identified as effective treatments for Hodgkin’s disease. We compared these regimens as initial chemotherapy for Hodgkin’s disease. Patients and Methods: Adult patients (N = 856) with advanced Hodgkin’s disease were randomly assigned to treatment with ABVD or MOPP/ABV. The major end points were failure-free and overall survival, life-threatening acute toxicities, and serious long-term toxicities, including cardiomyopathy, pulmonary toxicity, myelodysplastic syndromes (MDS), and secondary malignancies. Results: The rates of complete remission (76% v 80%, P = .16), failure-free survival at 5 years (63% v 66%, P = .42), and overall survival at 5 years (82% v 81%, P = .82) were similar for ABVD and MOPP/ABV, respectively. Clinically significant acute pulmonary and hematologic toxicity were more common with MOPP/ABV (P = .060 and .001, respectively). There was no difference in cardiac toxicity. There were 24 deaths attributed to initial treatment: nine with ABVD and 15 with MOPP/ABV (P = .057). There have been 18 second malignancies associated with ABVD and 28 associated with MOPP/ABV (P = .13). Thirteen patients have developed MDS or acute leukemia: 11 were initially treated with MOPP/ABV, and two were initially treated with ABVD but subsequently received MOPP-containing regimens and radiotherapy before developing leukemia (P = .011). Conclusion: ABVD and the MOPP/ABV hybrid are effective therapies for Hodgkin’s disease. MOPP/ABV is associated with a greater incidence of acute toxicity, MDS, and leukemia. ABVD should be considered the standard regimen for treatment of advanced Hodgkin’s disease.

Secondary acute myelogenous leukemia following safe exposure to etoposide.

1997 ◽  
Vol 15 (4) ◽  
pp. 1583-1586 ◽  
Author(s):  
K C Stine ◽  
R L Saylors ◽  
J R Sawyer ◽  
D L Becton
Keyword(s):  
Acute Myelogenous Leukemia ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Disease Patient ◽  
Myelogenous Leukemia ◽  
Chromosome 11 ◽  
Acute Myelogenous ◽  
Involved Field ◽  
Involved Field Radiotherapy ◽  
French American British

PURPOSE To present two patients as illustrations of the risk of developing secondary acute myelogenous leukemia (sAML) when theoretically safe doses of etoposide (VP-16) are used. PATIENTS AND METHODS Patient no. 1 was a 15-year-old white girl diagnosed with stage IIa Hodgkin's disease. She was treated with a combination of vincristine, doxorubicin, bleomycin, and VP-16 (2 g/m2 total) over 4 months, followed by 25.5 Gy of involved-field radiotherapy. Patient no. 2 was an 11-year-old white boy diagnosed with virus-associated hemophagocytic syndrome (VAHS). He was treated with VP-16 intravenously (IV) and orally (0.3 g and 2.8 g/m2, respectively). RESULTS Patient no. 1 developed AML 16 months from the diagnosis of Hodgkin's disease. Patient no. 2 developed AML 26 months from diagnosis. Both bone marrows were consistent with French-American-British (FAB) M4 disease. Both patients had abnormalities of the long arm of chromosome 11. CONCLUSION The use of low-dose or oral VP-16 can be associated with the development of sAML. Clinicians should be cautious in the use of VP-16 in low-risk diseases.

Replacing Gemtuzumab Ozogamicin With Idarubicin In Frontline Fludarabine, Cytarabine and G-CSF Based Regimen Does Not Compromise Outcome In Core Binding Factor Acute Myelogenous Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3971-3971 ◽  
Author(s):  
Gautam Borthakur ◽  
Jorge E. Cortes ◽  
Farhad Ravandi ◽  
Graciela Nogueras Gonzalez ◽  
Rajyalakshmi Luthra ◽  
...  
Keyword(s):  
Overall Survival ◽  
Low Dose ◽  
Gemtuzumab Ozogamicin ◽  
Myelogenous Leukemia ◽  
Core Binding Factor ◽  
Free Survival ◽  
Log Reduction ◽  
Binding Factor ◽  
Acute Myelogenous

Abstract A regimen comprising of fludarabine, cytarabine, G-CSF and gemtuzumab ozogamicin (FLAG-GO) has been our frontline treatment regimen for patients with core binding factor acute myelogenous leukemia (CBF-AML) and among 50 patients with median follow up of over 3 years, this regimen resulted in overall survival (OS) and relapse free survival (RFS) of 78% and 85% respectively. This is clearly better than our historical data with idarubicin and cytarabine based regimens (Borthakur et al. JCO. Vol 28, No 15 suppl; 2010:6552). After withdrawal of GO from the market, it has been substituted by low dose idarubicin at 6 mg/m2 on days 3 and 4 in induction and in one post remission cycle during cycles 3-6 (FLAG-Ida). So far 38 patients have been treated with FLAG-Ida (median follow up 1 year) with all patients achieving complete remission. The current report is part of the planned analysis to ensure that patient outcomes have not been compromised by the change in regimen. Univariate and multivariate (MVA) Cox proportional hazards regression was used to identify association of the clinical variables with overall survival (OS), event free survival (EFS) and time to relapse (TTR). Event is defined as death from any cause or relapse. Treatment regimen (FLAG-GO or FLAG-Ida) were included as variables in the analysis. Apart from relevant clinical variables, reduction in fusion transcript ratio (in reference to ABL gene transcript compared to that at diagnosis) at time points 1 month (≥3 log reduction yes/no) and 3 month (≥3 log reduction yes/no) and presence of any mutation (RAS, KIT, FLT3 yes/no) were also added as variables. Stepwise backwards selection method was used to remove variables that did not remain significant in the multivariate model (p ≥ 0.15). T(8;21) is the cytogenetic abnormality in 52% of all 88 patients. Median age of all patients is 51 (range, 19-78 years) and 48% are female. Median time to 3 log reduction in transcript ratio was 1 month (range, 1-22 months). Complete remission rate with or without platelet recovery has been 98% with 2 induction deaths. Kaplan-Meier analysis showed OS (Fig.1), EFS and TTR were not significantly different FLAG-GO and FLAG-Ida regimens. By MVA, OS, EFS and TTR are not different among these regimens (p > 0.5). Three log or more reduction in transcript ration at 1 month was associated with better OS (p=.03) and EFS (p=.008) (not TTR) in MVA. Presence of KIT, RAS or FLT3 gene mutation did not impact outcomes studied. In conclusion, replacing GO with low dose idarubicin in a front-line FLAG regimen does not seem to compromise the excellent outcomes with such a regimen in CBF AML. Disclosures: No relevant conflicts of interest to declare.

Cep Regimen (Ccnu, Etoposide, Prednimustine) for Relapsed/Refractory Hodgkin's Disease

1994 ◽  
Vol 80 (6) ◽  
pp. 438-442 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Enza Barbieri ◽  
Maurizio Bendandi ◽  
Francesco Perini ◽  
Filippo Gherlinzoni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Tumor Burden ◽  
Bulky Disease ◽  
First Relapse

Aims and background Although initial treatment of Hodgkin's disease induces a complete remission in most patients, approximately 50% of patients with advanced disease will not achieve a complete remission or will relapse following the first complete remission. Patients and methods Twenty-three patients with relapsed/resistant Hodgkin's disease, observed between January 1991 and October 1993, underwent CEP combination chemotherapy (CCNU, etoposide, prednimustine). All patients had previously received MOPP and ABVD regimens, in combination at diagnosis or sequentially (at diagnosis and at the first relapse). Results Thirteen (56%) patients achieved complete responses and 4 (18%) had partial responses. Two partial responders obtained a complete remission after a successive autologous bone marrow transplantation. The complete remission was not influenced by the timing of MOPP and ABVD treatments, presence of extranodal involvement or presence of bulky disease, but was affected by the presence of a primary disease refractory to the first standard programs. All the complete responders but 2 were alive and relapse-free at a median follow-up of 15 months; no major toxic effects were recorded. Conclusions These data suggest, as did those of other studies, that CEP is an effective regimen in patients with Hodgkin's disease in first or second relapse, also to reduce the tumor burden and to determine chemosensitivity before contingent bone marrow or peripheral blood stem cell support.

Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP.

1991 ◽  
Vol 9 (8) ◽  
pp. 1409-1420 ◽  
Author(s):  
D L Longo ◽  
P L Duffey ◽  
V T DeVita ◽  
P H Wiernik ◽  
S M Hubbard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Advanced Stage ◽  
Free Survival ◽  
Disease Free

One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival.

The CXCR4 Score: A New Prognostic Marker in Acute Myelogenous Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1072-1072 ◽  
Author(s):  
Anke C. Spoo ◽  
William G. Wierda ◽  
Jan A. Burger
Keyword(s):  
Overall Survival ◽  
Relapse Rate ◽  
Acute Myelogenous Leukemia ◽  
Prognostic Significance ◽  
Surface Expression ◽  
Cxcr4 Expression ◽  
Myelogenous Leukemia ◽  
Fluorescence Intensity Ratio ◽  
Acute Myelogenous

Abstract Despite major improvements in the understanding and treatment of certain leukemias during the past years, the overall survival of patients with acute myelogenous leukemia (AML) remains poor and new prognostic markers and therapeutic strategies are urgently needed. The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 play key roles in retention of hematopoietic cells in the marrow microenvironment and release into the circulation. Rambouts and colleagues recently reported that CXCR4 expression on AML cells correlates with Flt3 mutations and prognosis (Blood 104: 550-57, July 2004). The aim of our study is to evaluate the prognostic significance of CXCR4 surface expression by AML blasts. Ninty newly diagnosed patients with AML were were divided into three groups based on expression of CXCR4 by AML blasts (CXCR4 score A–C). Group A contains patients with a mean fluorescence intensity ratio (MFIR) for CXCR4 <5 (n=32), group B: MFIR 5–10 (n=26), and group C: MFIR >10 (n=32). MFIR was calculated by divding the mean flourescence intensity for CXCR4 by that for the non-specific isotype control of the respective sample and indicates the level of CXCR4 expression. The characteristics for each group are summarized in Table 1. Previously, we demonstrated that CXCR4 receptors on AML cells mediate adesion and induce migration beneath marrow stromal cells (Burger JA,et al., Br J Haematol. 122: 579–89, August 2003). Because adhesion to stromal elements can affect survival and induce adhesion-mediated drug resistance, antagonists of the CXCR4/SDF-1 axis may increase the efficacy of current treatments. We conclude that CXCR4 expression at time of diagnosis correlates with leukocytosis, LDH, blast persistence after first therapy, relapse rate, and survival. Therfore, CXCR4 expression in AML may be an important progostic factor for complete remission and survival. As such, CXCR4/SDF-1 interaction may provide the basis for a novel therapeutic approach in AML. Characteristic Score A (N=32) Score B (N=26) Score C (N=32) Median CXCR4 MFIR (range) 2.8 (1.0–4.9) 6.9 (5.1–9.4) 17.2 (10.3–73.4) Median Age (range) 62.0 (21–89) 59.5 (18–80) 65.0 (32–93) Median WBC (range) 2.3 (1.0–14.0) 10.2 (10.2–17) 30.0 (2.7–240) Median PLT (range) 56.0 (8–211) 86.0 (13.6–265) 82.5 (4–218) Median LDH (range) 251.5 (140–2637) 368.0 (187–1489) 357.0 (144–2760) Unfavorable Cytogenetics 4/28 10/24 7/27 blast persistence after first therapy N=6, 22.2% N=13, 65% N=14, 73.7% Relapse Rate 13.8% 52.4% 40% Total Deaths N=7, 21.9% N=13, 50% N=17, 53.1% Mean overall survival (months) 12.4±11.9 10.3±9.8 8.3±7.4 Mean follow-up (months) 12.0±19.7 Median Overall Survival (months) 9.0 (2–52) 6.5 (0–42) 7.0 (0–25) Median follow-up (months) 7.0 (0–52) Table

Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial.

1995 ◽  
Vol 13 (1) ◽  
pp. 11-18 ◽  
Author(s):  
E Archimbaud ◽  
X Thomas ◽  
V Leblond ◽  
M Michallet ◽  
P Fenaux ◽  
...  
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Disease Free Survival ◽  
Autologous Bone Marrow ◽  
Myelogenous Leukemia ◽  
Sequential Chemotherapy ◽  
Long Term Follow Up ◽  
Acute Myelogenous ◽  
First Relapse ◽  
Previously Treated

PURPOSE To confirm and extend encouraging preliminary results of timed sequential chemotherapy (TSC) in patients with previously treated acute myelogenous leukemia (AML). PATIENTS AND METHODS We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months. RESULTS Sixty percent of patients, with a 95% confidence interval (CI) ranging from 51% to 68%, achieved complete remission (CR), including 44% (CI, 32% to 57%) of refractory patients and 76% (CI, 64% to 86%) of late first-relapse patients (P = .0002). Twenty-nine percent of patients did not respond to therapy, and 11% died from toxicity. Median duration of neutropenia and thrombocytopenia was 31 days and 29 days, respectively. Severe nonhematologic toxicity included sepsis in 54% of patients and mucositis in 23%. Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13. Median survival of patients who did not have transplantation performed is 7 months, with 11% (CI, 4% to 18%) survival at 5 years. Median disease-free survival (DFS) is 8 months with 20% (CI, 8% to 32%) DFS at 5 years. Twenty-eight percent (CI, 15% to 44%) of nontransplanted patients who achieved CR had an inversion of CR duration. Previous refractoriness was the main factor associated with poor prognosis for CR achievement, DFS, and survival. CONCLUSION These results confirm initial reports on TSC and show that approximately 20% of patients with first relapse after therapy can enjoy prolonged DFS using chemotherapy only.

Mantle irradiation alone for selected patients with laparotomy-staged IA to IIA Hodgkin's disease: preliminary results of a prospective trial.

1995 ◽  
Vol 13 (4) ◽  
pp. 947-952 ◽  
Author(s):  
P M Mauch ◽  
G P Canellos ◽  
L N Shulman ◽  
B Silver ◽  
N J Tarbell ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Prospective Trial ◽  
Results Of Treatment ◽  
Early Results ◽  
Negative Laparotomy

PURPOSE To determine the feasibility of omitting prophylactic paraaortic irradiation in selected patients with laparotomy-staged (pathologically staged [PS]) IA to IIA Hodgkin's disease. PATIENTS AND METHODS We initiated a prospective single-arm trial in October 1988 to study the role of mantle irradiation alone in selected PS IA to IIA patients with Hodgkin's disease. A total of 37 patients have been entered onto this trial. Entrance criteria included nodular sclerosis (NS) or lymphocyte predominance (LP) histology, absence of B symptoms, disease limited above the carina, and a negative laparotomy. Results of treatment of 23 patients in the prospective trial, monitored off treatment for > or = 1 year, are presented. Twenty-three additional PS IA to IIA patients, treated with mantle irradiation alone from 1970 to 1987, were analyzed as a comparison group. The median follow-up durations were 32 and 113 months, respectively, for the two groups. RESULTS The 4-year actuarial rates of freedom from relapse and overall survival are 83% and 100%, respectively, for the prospective trial. The 10-year actuarial rates of freedom from relapse and overall survival are 83% and 89%, respectively, for retrospectively studied patients. There have been five recurrences among 46 patients who received mantle irradiation alone, all with a component of relapse below the diaphragm. CONCLUSION These early results support the use of mantle irradiation alone in selected PS IA to IIA patients with NS or LP histology. Relapses, although rare, have occurred predominantly below the diaphragm. This suggests the need for continued long-term surveillance of abdominal and pelvic nodes in this group of treated patients.

Stage IA and IIA supradiaphragmatic Hodgkin's disease: prognostic factors in surgically staged patients treated with mantle and paraaortic irradiation.

1988 ◽  
Vol 6 (10) ◽  
pp. 1576-1583 ◽  
Author(s):  
P Mauch ◽  
N Tarbell ◽  
H Weinstein ◽  
B Silver ◽  
T Goffman ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Hodgkin's Disease ◽  
Early Stage ◽  
Hodgkin’S Disease ◽  
Stage Ia ◽  
First Relapse ◽  
Therapeutic Recommendations ◽  
Actuarial Risk

A total of 315 pathologically staged (PS) patients with IA and IIA Hodgkin's disease (HD) were treated with mantle and paraaortic irradiation, and evaluated for freedom-from-first relapse (FFR), survival, prognostic factors, and long-term complications. The 14-year actuarial FFR and survival were 82% and 93%, respectively, with a median follow-up time of 9 years. Mediastinal size was the only factor that predicted for a lower FFR, P less than .001. Forty-nine patients have developed recurrent HD. Thirty-six patients are disease-free following retreatment and only 13 patients have died of HD. Patients with mixed cellularity (MC) histology were more likely to relapse below the diaphragm (11%) as compared with patients with nodular sclerosis (NS) (5.1%) or lymphocyte predominant (LP) (3.6%) histology. These relapses were often associated with bulky pelvic nodal adenopathy and salvage treatment with chemotherapy alone often failed to control recurrent disease. Alternative diagnostic and therapeutic recommendations are presented for these patients. Thyroid abnormalities represented the most common long-term complication with an actuarial risk at 16 years of 37%. Major complications were rare. Mantle and paraaortic irradiation is associated with a high FFR and a low risk of complications and should remain standard treatment for early-stage HD.

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