Allogeneic, syngeneic, and autologous marrow transplantation for Hodgkin's disease: the 21-year Seattle experience.

1993 ◽  
Vol 11 (12) ◽  
pp. 2342-2350 ◽  
Author(s):  
J E Anderson ◽  
M R Litzow ◽  
F R Appelbaum ◽  
G Schoch ◽  
L D Fisher ◽  
...  

PURPOSE To analyze results of 127 patients undergoing myeloablative therapy followed by marrow transplantation for relapsed or refractory Hodgkin's disease. PATIENTS AND METHODS Twenty-three patients had primary refractory disease, 34 were in early first relapse or second complete remission (CR), and 70 had refractory first relapse or disease beyond second CR. Preparative regimens included total-body irradiation (TBI) and chemotherapy (n = 61) or chemotherapy only (n = 66). Sixty-eight patients received autologous marrow, six syngeneic marrow, and 53 allogeneic marrow. RESULTS The 5-year actuarial probabilities of survival, event-free survival (EFS), relapse, and nonrelapse mortality for the entire group were 21%, 18%, 65%, and 49%, respectively. HLA-identical allogeneic marrow recipients had a statistically lower relapse rate compared with recipients of autologous marrow, but survival, EFS, and nonrelapse mortality rates were not significantly different. In the multivariate analysis, higher performance status and absence of bulky disease predicted for improved EFS and lower relapse rates, while fewer prior treatment regimens predicted for improved EFS and lower nonrelapse mortality rates. Additionally, the univariate analysis showed that patients who underwent transplantation with disease refractory to chemotherapy or beyond second CR had a worse outcome compared with those who had less advanced disease. CONCLUSION Outcome with transplantation for patients with Hodgkin's disease is improved if transplantation is performed early after relapse when disease burden is less, tumor chemosensitivity is greater, and the patient is likely to have a better performance status. The use of HLA-matched sibling marrow results in a lower relapse rate and, thus, for some individuals, may be preferable to the use of autologous marrow.

1989 ◽  
Vol 7 (8) ◽  
pp. 1039-1045 ◽  
Author(s):  
G L Phillips ◽  
D E Reece ◽  
M J Barnett ◽  
J M Connors ◽  
J W Fay ◽  
...  

Eight patients with refractory Hodgkin's disease received intensive combination chemotherapy conditioning with cyclophosphamide, carmustine (BCNU), and etoposide (VP 16-213), and allogeneic marrow transplants. All patients achieved complete responses. Three patients relapsed; two died of Hodgkin's disease and one of chronic graft-v-host disease (GVHD) and infection. In all, four patients died due to transplant-related toxicity. One patient developed a fatal B-cell lymphoproliferative disorder soon after transplantation, and died without evidence of Hodgkin's disease. One patient is alive and free of progression 29 months after transplantation. These data indicate that allogeneic marrow transplantation may be considered as therapy for selected patients with advanced Hodgkin's disease and, despite substantial toxicity, will occasionally result in long-term responses. Better patient selection would likely improve results.


1985 ◽  
Vol 3 (11) ◽  
pp. 1490-1494 ◽  
Author(s):  
F R Appelbaum ◽  
K M Sullivan ◽  
E D Thomas ◽  
C D Buckner ◽  
R A Clift ◽  
...  

Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.


1994 ◽  
Vol 80 (6) ◽  
pp. 438-442 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Enza Barbieri ◽  
Maurizio Bendandi ◽  
Francesco Perini ◽  
Filippo Gherlinzoni ◽  
...  

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.


1986 ◽  
Vol 4 (4) ◽  
pp. 472-479 ◽  
Author(s):  
M J Crnkovich ◽  
R T Hoppe ◽  
S A Rosenberg

Between 1968 and 1982, 126 patients with pathologic stage (PS) IIB Hodgkin's disease were treated at Stanford University with either irradiation alone or irradiation combined with chemotherapy. Actuarial survival and freedom from relapse rates at 10 years for the overall group were 81% and 74% respectively, with no statistically significant difference between the treatment approaches. The impact of the severity and number of constitutional (B) symptoms, as defined by the Ann Arbor Conference, was analyzed. Patients who presented with all three B symptoms had significantly poorer survival and freedom from relapse compared with those patients with only one or two B symptoms (for survival differences, P = .005 and .007; for freedom from relapse differences, P = .002 and .04). Male sex was the only other prognostic factor that correlated with a poor outcome. At 10 years, the survival rate was 66% for males v 84% for females (P = .01), and the freedom from relapse rate was 75% for males v 89% for females (P = .02). The presence of extralymphatic sites of involvement, age greater than 40, or involvement of greater than three lymphoid sites had no significant adverse effect on either freedom from relapse or survival. Patients with large mediastinal masses treated with irradiation alone had a 10-year freedom from relapse rate of 54% v 81% for those treated with combined-modality therapy (P = .15), but there was no significant difference in survival rates (85% for irradiation alone v 71% for combined modality therapy). Treatment recommendations for stage IIB Hodgkin's disease are discussed.


1998 ◽  
Vol 16 (1) ◽  
pp. 19-26 ◽  
Author(s):  
J H Glick ◽  
M L Young ◽  
D Harrington ◽  
R L Schilsky ◽  
T Beck ◽  
...  

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.


2002 ◽  
Vol 20 (3) ◽  
pp. 630-637 ◽  
Author(s):  
Sandra J. Horning ◽  
Richard T. Hoppe ◽  
Sheila Breslin ◽  
Nancy L. Bartlett ◽  
B. William Brown ◽  
...  

PURPOSE: To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin’s disease. PATIENTS AND METHODS: One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin’s disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (≥ 5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up. RESULTS: With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P < .0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years. CONCLUSION: These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin’s disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.


1991 ◽  
Vol 9 (10) ◽  
pp. 1871-1879 ◽  
Author(s):  
D E Reece ◽  
M J Barnett ◽  
J M Connors ◽  
R N Fairey ◽  
J W Fay ◽  
...  

Fifty-six consecutive patients with advanced Hodgkin's disease considered incurable with further conventional chemotherapy were entered into a protocol that included high-dose cyclophosphamide (7.2 g/m2), carmustine (BCNU; 0.6 g/m2), and etoposide (VP16-213; 2.4 g/m2) (CBV) followed by autologous bone marrow transplantation (BMT). Prior combination chemotherapy had failed in all the patients, and all but five had been previously treated with both mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, and vinblastine with or without dacarbazine (ABV[D]). Thirty-four eligible patients received short-course conventional chemotherapy and/or involved-field radiotherapy before CBV. However, formal restaging was not performed after these conventional therapies; ie, the therapies were not used to select responding patients for transplantation, and all who received such therapy subsequently received CBV and autologous marrow grafts. Forty-four patients (80%; 95% confidence interval [CI], 69% to 91%) achieved a complete response after CBV and BMT. Performance status at protocol entry and the use of conventional cytoreduction therapy before CBV correlated with response. Median follow-up is now 3.5 years (range, 2.5 to 5.0 years). Kaplan-Meier estimates for overall and event-free survival 5 years after transplant are 53% (95% CI, 37% to 67%) and 47% (95% CI, 33% to 60%), respectively. In a univariate analysis, patients with a normal performance status and those without constitutional ("B") symptoms at protocol entry had an improved overall and event-free survival. In a multivariate analysis, only a normal performance status remained significant. Disease progression occurred in 17 patients at an actuarial rate of 39% (95% CI; 26% to 56%) and occurred at previous sites of active disease in all but one patient; our analysis did not identify prognostic factors for progression. Toxic deaths, caused by either neutropenic sepsis or interstitial pneumonitis (IP), occurred in 12 patients (21%; 95% CI, 10% to 32%). CBV with autologous marrow support can produce durable remissions in a substantial number of patients with Hodgkin's disease considered incurable with conventional measures. Regimen refinements may even further improve the therapeutic index of BMT in this malignancy.


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