High-dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin lymphoma: Prognostic features and outcomes

Meharry Medical College, Nashville, Tennessee, United States
Leukemia and Lymphoma (Impact Factor: 2.89). 09/2007; 48(9):1728-35. DOI: 10.1080/10428190701534374
Source: PubMed


Between January 1990 and April 2001, 115 patients received high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) for relapsed or refractory Hodgkin lymphoma (HL). With a median follow-up of 58 months (range, 1 - 175 months), 5-year progression-free survival (PFS) and overall survival (OS) were 46% and 58%, respectively. Twelve patients with primary refractory disease had a 5-year PFS of 41% and OS of 58%, not significantly different from those of the remaining cohort. Early and overall regimen related mortality were 7% and 16%, respectively. Male gender (P = 0.04) and a time to relapse (TTR) < 12 months (P = 0.03) were associated with decreased OS by univariate analysis. In multivariate analysis, TTR < 12 months remained statistically significant (P = 0.04). We have confirmed that HDT and ASCT result in long-term survival for a proportion of patients with relapsed or refractory HL. All patients, including those with primary refractory disease, benefited from HDT and ASCT.

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    ABSTRACT: Many patients with Hodgkin lymphoma are cured with initial therapy, although a portion of patients will experience primary induction failure or disease relapse. Pathologic confirmation of refractory or relapsed Hodgkin lymphoma is important. Following two to four cycles of non-cross-resistant salvage chemotherapy, the standard of care is high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT), which is associated with long-term event-free survival rates of 45-68%. Of note, survival rates for studies integrating total lymphoid irradiation into the autologous HSCT-conditioning regimen are among the highest reported for relapsed/refractory Hodgkin lymphoma. Further treatment options are available for patients not fit to proceed to HSCT, for relapsed disease after autologous HSCT, and for 'high-risk' Hodgkin lymphoma including chemotherapy-resistant disease. Allogeneic HSCT is a valid treatment option, as a graft-vs.-Hodgkin-lymphoma effect has been demonstrated. In addition, novel targeted treatments are being investigated such as receptor-specific antibodies, radiolabeled antibodies, antiapoptotic agents including inhibitors of the nuclear factor-kappaB complex or X-linked inhibitor of apoptosis proteins, transcription pathway modulators such as histone deacetylase and mTOR inhibitors, and Epstein-Barr virus-directed therapy. Continued translational and collaborative prospective clinical research efforts are needed in order to continue to increase the survival rates for Hodgkin lymphoma and to lessen the toxicities associated with lymphoma-related therapy.
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    ABSTRACT: Patients with relapsed or refractory Hodgkin's disease (HD) are routinely treated with intensive chemotherapy followed by autologous stem cell transplantation (ASCT). The objectives of the study were to evaluate ASCT in this subset of patients by assessing its toxicity in terms of transplant related mortality (TRM), hematopoietic recovery and need for transfusion support, and efficacy in terms of complete remission (CR) achieved as well as long-term efficacy expressed in patient overall survival (OS). From February 1995 until October 2006, a total of 53 patients with active HD (28 male and 25 female, aged 18-60, median 29) received BEAM myeloablative treatment followed by ASCT. All patients received heavy prior treatment with a median of 2 different lines of chemotherapy (range 1-6) and a median of 8 chemotherapeutic cycles (range 2-15). A mean of 9.12 (range 1.03-32.6, SD 9.5) x 10(6)/kg CD34+ cells was reinfused, followed by filgrastim (median 8 days, range 4-22 days). The median time to WBC recovery (> 1 x 10(9)/L) was 10 (range 2-26) days, while platelets recovered (> 20 x 10(9)/L) in a median of 10 (range 4-30) days. During the post-transplant period, a mean of 16.3 platelet doses (range 0-77, SD 15.5) and 345.6 mL of RBC concentrate (range 0-1990, SD 478.4) was administered. A median of 3 febrile days (range 0-20) was observed. Of all patients, 43 (81.1%) achieved CR and 9 (17.0%) achieved partial remission. One patient died during the pancytopenic period (TRM 1.9%). The projected overall survival is 66.3% at 3948 days. Accordingly, in this group of patients with active disease at the time of transplantation, ASCT toxicity could be considered acceptable. A very high remission rate was achieved (CR+PR 98.1%). We conclude that BEAM myeloablative chemotherapy followed by ASCT is a very efficacious treatment for patients with relapsed or refractory HD.
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    ABSTRACT: High Dose Therapy (HDT) and Autologous hematopoietic stem-cell transplantation (ASCT) represents the best available treatment option for patients with primary refractory or relapsed Hodgkin's Lymphoma (HL). HDT and ASCT has also been used as part of the front-line treatment in patients with very unfavorable baseline prognostic features, such as high IPS, bulky and/or extranodal disease not responding to standard treatment, or with a positive PET scan after 2-4 cycles of first-line treatment. The procedure usually follows an effective cytoreduction with 2-4 cycles of a second-line or salvage chemotherapy, the last cycle of which can also be used as a mobilization regimen. There is no agreement on which is the best preparatory regimen. TBI-or TLI-containing regimens tend to be abandoned, because they have been associated with increased early post-ASCT morbidity and mortality. The most commonly used conditionning regimens are BEAM, CBV and BEAC. Efforts to intensify these regimens have produced substantial lung toxicity, mainly attributed to BCNU. Chemosensitive disease, longer than 12 months duration of previous remission, female sex, age <50 or 60 years, an IPS lower than 4 at diagnosis and at SCT, good Karnovsky performance status, disease status at ASCT, normal serum LDH, absence of anemia, B symptoms, advanced stage, extranodal or bulky disease and mediastinal involvement at SCT and use of less than 3 different regimens have been recognized as factors predicting for a favourable outcome of ASCT. For patients sharing adverse prognostic factors, the application of tandem autotransplants has been suggested that may be more beneficial. It has clearly been recognized that long-term survivors of HL, either Correspondence/Reprint request: Dr. Argiris S. Symeonidis, Ass.
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