High-Dose Chemotherapy Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Lymphocyte Predominant Hodgkin’s Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3061-3061 ◽  
Author(s):  
Philip Bierman ◽  
Hina Naushad ◽  
Fausto Loberiza ◽  
R. Gregory Bociek ◽  
Julie M. Vose ◽  
...  

Abstract Lymphocyte Predominant Hodgkin’s Disease (LPHD) is a B-cell lymphoma that may require different treatment and may have a different natural history than classical Hodgkin’s disease. Although AHSCT is accepted therapy for patients with relapsed and refractory classical Hodgkin’s disease, there is little information regarding transplantation for LPHD. We performed a retrospective analysis of 19 patients who were treated with AHSCT for relapsed or refractory LPHD at the University of Nebraska Medical Center between April, 1987 and October, 2002. Biopsies of all LPHD patients were reviewed to confirm the diagnosis according to the WHO classification. Patients with a prior or concurrent diagnosis of classical Hodgkin’s disease or non-Hodgkin’s lymphoma were excluded. There were 18 men and 1 woman. Median age was 33 years (range 19–52). Thirteen patients (68%) received 1–2 chemotherapy regimens prior to AHSCT, and 6 patients (32%) received 3 or more regimens. Nine patients (47%) received radiation therapy prior to AHSCT. Five patients (26%) had extranodal disease at the time of AHSCT. Five patients (26%) were transplanted with autologous bone marrow, and 14 patients (74%) received peripheral blood stem cells. Six patients (32%) were transplanted with BEAM (carmustine, etoposide, cytarabine, melphalan), and 13 patients (68%) were treated with CBV (cyclophosphamide, carmustine, etoposide). The results of AHSCT for the 19 patients with LPHD were compared with 229 patients in our database who received AHSCT for relapsed and refractory nodular sclerosis Hodgkin’s disease during the same time period. The characteristics of the groups were similar with respect to age, disease status at the time of AHSCT, stage at AHSCT, amount of treatment prior to AHSCT, and interval between diagnosis and AHSCT. Patients with LPHD were more likely to be males (p<0.001), less likely to have received radiation prior to AHSCT (p=0.06), and more likely to have been transplanted with peripheral blood stem cells (p=0.05). The actuarial 5-year progression-free survival following AHSCT for patients with LPHD and nodular sclerosis Hodgkin’s disease was 40% (95% CI 18% to 61%) and 39% (95% CI 33% to 45%), respectively (p=0.30). The actuarial 5-year overall survival following AHSCT for patients with LPHD and classical Hodgkin’s disease was 56% (95% CI 30% to 75%) and 53% (95% CI 46% to 59%), respectively (p=0.36). A multivariate analysis comparing patients with LPHD and those with nodular sclerosis Hodgkin’s disease was performed. The relative risk of treatment failure following AHSCT for patients with nodular sclerosis histology was 1.14 (95% CI 0.62 to 2.12; p=0.67), and the relative risk of death was 1.22 (95% CI 0.62 to 2.41; p=0.56). These results demonstrate that long-term progression-free survival and overall survival can be achieved following high-dose therapy and AHSCT for patients with LPHD. Furthermore, no significant differences in progression-free survival and overall survival were identified when results of AHSCT for LPHD and nodular sclerosis Hodgkin’s disease were compared. Although none of the LPHD patients were treated with newer agents such as gemcitabine or rituximab prior to AHSCT, this analysis suggests that high-dose therapy followed by AHSCT may be used for patients with relapsed and refractory LPHD as well as classical Hodgkin’s disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3400-3400
Author(s):  
Hartmut Goldschmidt ◽  
Gerlinde Egerer ◽  
Ute Hegenbart ◽  
Markus Munder ◽  
Thomas Hielscher ◽  
...  

Abstract Abstract 3400 Poster Board III-288 To analyse the impact of complete response (CR), near CR (nCR) and very good partial response (VGPR) before and after first high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) on overall survival (OS) and progression-free survival (PFS), we evaluated all patients with multiple myeloma (MM) who underwent an ASCT in frontline treatment at our centre. The transplantations were performed between June 1992 and February 2009 giving a minimum follow up of 5 months after ASCT. The retrospective analysis included a total of 994 patients (579 males and 415 females) with a median age of 58 years at time of first ASCT (range 25 - 76 years). Median follow-up after first ASCT was 5.8 years. All patients suffered from symptomatic MM. Before induction treatment 48%, 31% and 21% of patients were in ISS-stage I, II and III, respectively. The following induction regimes were applied prior to HDT: VAD (n=683), TAD (n=74), PAD (n=64), and other regimes (n= 173). The patients were treated with HDT once (n= 460), twice (n=437) or thrice (n=97). 91 patients received an allogeneic SCT, 30 of these before first progression after ASCT. These were censored for PFS at time of allogeneic SCT. Maintenance therapy (interferon n=332, thalidomide n=203, bortezomib n=48 or others n=13) was administered in 596 patients. Overall survival and progression-free survival were calculated from the time of first ASCT. The median OS time was 5.7 years and the median PFS was 2.2 years. Log-rank test, univariate and multivariate Cox PH regression as well as landmark analyses were utilized to assess the prognostic impact of response. We analysed the effect of achievement of CR, of nCR or CR and of VGPR or CR or nCR before and after HDT, respectively. Achieving CR or nCR is a highly significant prognostic factor for PFS and OS before (p<0.001 and p=0.01, respectively) and after first HDT (both p<0.001). The group including VGPR showed superior outcome when assessed after HDT, driven by the effect of CR/nCR. When adjusting for the effect of age, beta-2 microglobulin before ASCT, albumin before ASCT, new drugs before ASCT (thalidomide and bortezomib; yes/no), second ASCT within 9 months (yes/no), maintenance therapy (yes/no), and date of first ASCT, achieving CR or nCR remained a significant prognostic factor (PFS after ASCT: HR=0.66 [0.54;0.80], p<0.001; OS after ASCT: HR=0.65 [0.51;0.83], p=0.001). In addition, we analyzed the effect of duration of response compared to response achievement per se. Patients who sustained their remission (overall response = PR and better) at 3 yrs after first ASCT had a favourable prognosis with respect to OS compared to patients losing remission. Conclusion: In our single-center cohort achieving CR or nCR before and after first HDT is highly prognostic for PFS and OS in MM. Sustained duration of response is also associated with an improved prognosis (3 years landmark analysis). At our centre we recommend that patients not achieving at least an nCR should be treated with a second cycle of HDT. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1137-1145 ◽  
Author(s):  
R Chopra ◽  
AK McMillan ◽  
DC Linch ◽  
S Yuklea ◽  
G Taghipour ◽  
...  

Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5468-5468
Author(s):  
Kenneth A. Ault ◽  
Delvyn C. Case ◽  
Marjorie A. Boyd ◽  
Ervin J. Thomas ◽  
Frederick R. Aronson ◽  
...  

Abstract 29 patients with Stage III multiple myeloma have undergone transplantation at our institution over the past 10 years. Patient selection criteria included age less than 70 years, creatinine less than 2mg/ml, no active infection, cardiac ejection fraction &gt;40%, DLCO &gt; 50% of predicted and no other co-morbid conditions that would jeopardize sur-vival. In addition, there was demonstrated chemo-sensitivity of the disease with at least a 50% decrease in M-component and a decrease in marrow plasmacytosis to less than 10%. After treatment to maximal effect with VAD (3–6 cycles), peripheral blood stem cells were collected. The dose of CD34 positive cells ranged from 1.8 to 17.4 x106/kg. (median 11.4 x 106/kg). 8 patients treated prior to September 2000 received high dose therapy with Melphalan 140mg/m2 and fractionated TBI, 150cGy bid for 5 doses. Patients treated after September 2000 received Melphalan 200mg/m2 without radiation. The median age at transplantation was 52 years (range 29 to 71). There were no treatment related deaths. Days to achieve AGC&gt;500/ul ranged from 5 to 13 (average 6.8). The median length of follow up is 2.7 years. Currently 23 patients are alive, and 18 are free from progression. Overall survival at 5 years is 79%. Progression-free survival at 5 years is 43%. Figure Figure Our experience suggests that carefully selected patients with chemo-responsive multiple myeloma have relatively high rates of overall and progression free survival when compared to results reported for a broader population of patients.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5432-5432
Author(s):  
Ambuj Kumar ◽  
Benjamin Djulbegovic ◽  
Heloisa P. Soares

Abstract Background: Hodgkin disease (HD) is a potentially curable lymphoma with overall survival exceeding 60% at 10 years. However, patients with relapsed Hodgkin’s disease have a dismal prognosis when treated with conventional salvage chemotherapy. The primary objective of our systematic review/meta-analysis was to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with relapsed Hodgkin’s disease which has not been done before. Methods: Data search of published studies included Medline (1966–2006), Cochrane library and hand search of references. Studies were included if they were randomized controlled trials of HSCT versus conventional chemotherapy only. Data were extracted on benefits as well as harms (overall survival, event-free survival, and treatment related mortality). All data extraction was done in duplicate independently. Results: Out of 47 identified studies only 2 met the inclusion criteria of the current systematic review. Overall survival was similar for HSCT and conventional chemotherapy arms (see figure 1) with a pooled hazard ratio (HR) of 0.69 (95%CI 0.40, 1.18, p=0.2). However, the event-free survival was better in the HSCT arm than the conventional chemotherapy alone group (HR = 0.59, 95%CI 0.41, 0.85, p=0.005). Treatment related mortality was similar in both groups. (HR = 0.40, 95%CI 0.11, 1.44, p=0.2). Conclusion: Results from our meta-analysis indicate that treatment with HSCT compared with conventional chemotherapy only improves event free survival without excessive toxicity. However, overall survival was not affected by the HSCT therapy. In summary patients with relapsed Hodgkin’s disease should be offered HSCT therapy. Role of transplant in relapsed or resistant hodgkin’s disease Role of transplant in relapsed or resistant hodgkin’s disease


Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1137-1145 ◽  
Author(s):  
R Chopra ◽  
AK McMillan ◽  
DC Linch ◽  
S Yuklea ◽  
G Taghipour ◽  
...  

Abstract Although high-dose chemotherapy and autologous bone marrow transplantation (ABMT) are increasingly being used for the treatment of relapsed and resistant Hodgkin's disease, there have been few large, single-center studies reported with adequate follow-up to allow full evaluation of this therapeutic modality. We present 155 poor-risk Hodgkin's disease patients who received high-dose BEAM (BCNU, etoposide, cytosine arabinoside, and melphalan) chemotherapy and ABMT who have been studied over a period of 8 years. All patients had either not attained a remission on mechlorethamine, vincristine, procarbazine, prednisone-type therapy and had poor prognostic features at presentation, not attained a complete remission or relapsed within 1 year of an initial alternating regimen, or not attained remission with two or more lines of treatment. At the time of ABMT the relapse status of the patients was as follows: 46 patients were primarily refractory to induction therapy, 7 were good partial responders, 52 were in first relapse, 37 in second relapse, and 13 in third relapse. Seventy-eight patients had chemoresistant disease, 33 had chemosensitive disease at the time of ABMT, and 44 were untested for chemosensitivity at latest relapse. The procedure related mortality in the first 90 days post-ABMT of 10% overall. At 3 months 43 patients (28%) were assessed as complete responders, 72 patients had a partial response (46%), and 24 patients (16%) had no response or progression of disease. However, by 6 months, 53 (24%) patients were assessed as complete responders and 51 (33%) patients had nonprogressive disease. Forty-five patients had received radiotherapy post-ABMT to residual masses (41 patients) or to previous sites of bulk disease (4 patients). The actuarialoverall and progression-free survival at 5 years was 55% and 50%, respectively. On multivariate analysis patients with bulk (masses >10 cm), heavily pretreated patients (those receiving three or more lines of treatment) and females had a significantly poorer prognosis. Relapse status was also significant for progression-free survival in that patients in second (60%) and third relapse (70%) had a better prognosis than those in first relapse (44%) or with primary refractory disease (33%). Response to prior chemotherapy did not predict for progression-free survival. These results enable comparisons to be made between high-dose chemotherapy with ABMT and conventional dose salvage therapy. Furthermore, although the results as a whole are highly encouraging, certain groups carry an unfavorable prognosis.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2293-2293
Author(s):  
Christof Scheid ◽  
Peter Dreger ◽  
Dietrich W. Beelen ◽  
Martin Bornhäuser ◽  
Matthias Stelljes ◽  
...  

Abstract Abstract 2293 Poster Board II-270 Introduction: Although modern chemotherapy regimens achieve a high cure rate in primary Hodgkin's disease and relapsed patients can be salvaged by high dose chemotherapy with autologous stem cell transplantation there remains a subgroup of patients with early relapse despite high dose chemotherapy. The prognosis of these patients is dismal with further chemotherapy. Allogeneic transplantation has the potential to exert an alloimmune response against lymphoma cells and has therefor been offered to patients with relapsed or refractory Hodgkin's disease, in particular when a matched sibling donor was available. However only limited information on the feasability of allogeneic transplantion from an unrelated donor is available. Methods: We performed a retrospective analysis of allogeneic transplants for Hodgkins disease within the German Cooperative Transplantation Study Group. 18 centres have provided data on patient and donor characteristics, transplant procedure and outcome. Survival data were analysed by Kaplan-Meier and tested for differences by log rank test. Cumulative incidences for relapse, non-relapse mortality and graft-versus-host-disease were calculated in a competing risk model. Results: 79 patients with a median age of 30 years (range 14-59) were included. 65 (82%) patients had failed a previous autologous transplantation 582 days (median) before allotransplantation. Disease status at transplantation was CR in 17.6%, PR in 54.0%, stable disease in 9.5%, PD in 12.2%, and untreated relapse in 6.8%. Donors were matched related in 33%, mismatched related in 5%, matched unrelated in 42% and mismatched unrelated in 20%. With a median follow up of 19 months for surviving patients the median overall survival (OS) after allotransplant was 42 months with a 2 year survival of 51%. Non-relapse mortality was 21.1% after 12 and 24 months. The median progression-free survival was 14.6 months with a 2 year PFS of 42.0%. Patients relapsing after an autologous transplantation had a significantly better OS (median 53.7 vs 8.4 months, p=0.029) and PFS (22.0 vs 7.5 months, p=0.039) than patients without a prior autograft. No significant difference was seen for OS or PFS regarding the use of related or unrelated donors or disease status at transplant. Conclusions: Allogenic transplantation is a feasible option for high-risk patients with relapsed or refractory Hodgkins disease in particular after failing an autograft. Non-relapse mortality appears to be acceptable in view of the intensive prior treatment. Probabilities for overall survival and progression-free survival were similar after transplantation from a related or unrelated donor. Further optimisation strategies have to focus on on efforts to reduce the high relapse-rate after transplantation, thereby potentially increasing overall and progression free survival. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2010 ◽  
Vol 115 (12) ◽  
pp. 2348-2353 ◽  
Author(s):  
Morie A. Gertz ◽  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
David Dingli ◽  
...  

Autologous stem cell transplantation as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplantation. Previous medical literature has shown that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplantation. With the introduction of novel agents—immunomodulatory drugs and proteasome inhibitors—response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response (never responded or progressed during continuous therapy) after induction therapy with a regimen that contains thalidomide or lenalidomide. Unlike patients in reports published previously—before immunomodulatory drugs—patients who do not achieve partial remission have a significantly shorter overall survival from transplantation (73.5 vs 30.4 months) and a shorter progression-free survival (22.1 vs 13.1 months; P < .001). Absence of a response to induction therapy with thalidomide or lenalidomide predicts a poorer outcome after high-dose therapy.


1986 ◽  
Vol 4 (6) ◽  
pp. 838-846 ◽  
Author(s):  
V Vinciguerra ◽  
K J Propert ◽  
M Coleman ◽  
J R Anderson ◽  
L Stutzman ◽  
...  

A randomized clinical trial of combination chemotherapy for patients who relapsed following primary radiation therapy for Hodgkin's disease was conducted from 1975 to 1981 by the Cancer and Leukemia Group B (CALGB). One hundred thirteen patients were prospectively randomized to receive 12 cycles of either CVPP (CCNU, vinblastine, procarbazine, and prednisone), ABOS (bleomycin, vincristine [Oncovin; Lilly, Indianapolis], doxorubicin [Adriamycin, Adria Laboratories, Columbus, Ohio], and streptozotocin), or alternating cycles of CVPP and ABOS. The median length of observation for patients in this report is 4 years. Toxicities of the three treatment programs were primarily hematologic. Frequencies of complete response were 72% for CVPP, 70% for ABOS, and 82% for CVPP/ABOS (P = .37). Females and patients who had nodular sclerosing disease at initial diagnosis had significantly higher complete response rates. The 5-year disease-free survival for the complete responders was 55%; the 5-year overall survival was 60%. There were no significant differences among the treatments on disease-free survival (P = .78) or overall survival (P = .18). Age under 40 years was the only significant positive prognostic factor for disease-free survival (P = .095) and overall survival (P = .003). This study demonstrates no statistically significant advantage for alternating cycles of combination chemotherapy in affecting complete response frequency, disease-free survival, or overall survival as compared with therapy with CVPP or ABOS alone. However, the power to detect differences in these outcome parameters is somewhat limited by the sample sizes.(ABSTRACT TRUNCATED AT 250 WORDS)


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1318-1318
Author(s):  
William G. Martin ◽  
Kay M. Ristow ◽  
Joseph P. Colgan ◽  
Thomas M. Habermann ◽  
Stephen M. Ansell

Abstract Background: Bleomycin-containing chemotherapy regimens have become the mainstay of treatment in Hodgkin’s Disease (HD). The risk of bleomycin pulmonary toxicity (BPT) ranges from 0–46% and mortality rates range from 0–27%. Although there is no excepted standard treatment for BPT, corticosteroid treatment, withholding bleomycin from subsequent chemotherapy, and proceeding with a non-bleomycin containing regimen is the most common approach. We reviewed our experience to better delineate outcome and appropriate treatment in these patients. Methods: We reviewed all patients managed for HD at Mayo Clinic, Rochester, from January 1986 to February 2003. BPT was defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates, and no evidence for an infectious etiology. Results: A retrospective review identified 141 patients with HD treated with a bleomycin-containing regimen. The mean age of patients at diagnosis was 34 years. Fifty four percent were males. The histology was nodular sclerosing in 85%. The Hasenclever index was 0 in 15%, 1 in 35%, 2 in 24%, 3 in 16%, 4 in 9%, and &gt;5 in 1%. Frontline chemotherapy included ABVD in 57%, MOPP-ABV(D) in 33%, COPP-ABV in 8%, BEACOPP in 3%, and Stanford V in 2%. Forty one percent of patients received radiation. The 5-year overall survival (OS) and progression free survival (PFS) for all patients were 87% and 79% respectively. BPT was observed in 18% of patients (25/141). There was a significant decrease in OS, 63% in patients with BPT versus 90% in non-BPT patients at 5 years (p=0.0013). The mortality from BPT was 4.2% (6/141) in all patients and 24% (6/25) in patients who developed the pulmonary syndrome. These 6 patients all died within 9 months of their HD diagnosis from BPT. The Hasenclever index was 3 or less in 5 of these 6 patients. CR rates were equal at 91% and 93% in BPT and non-BPT patients respectively (p=0.299). Twenty two percent (31/141) of patients, either symptomatic or asymptomatic, had bleomycin omitted at any time from their regimen with no difference in OS or PFS, 83% versus 88% (p=0.369) and 82% versus 78% (p=0.853) respectively. The mean bleomycin dose was 84 mg/m2 (range of 20–180 mg/m2). Bleomycin dose had no impact on OS or PFS. In BPT patients subsequent non-bleomycin therapy included AVD 44%, MOPP-AV 31%, or no further chemotherapy 25%. The five-year OS was equal between the AVD and MOPP-AV groups at 91%. However in patients who received no further chemotherapy 5-year OS was 30% (p=0.0001). Conclusion: Bleomycin pulmonary toxicity (BPT) results in a significant decrease in OS survival at 5 years in patients being treated for Hodgkin’s Disease. In patients who do not die acutely from pulmonary toxicity both OS and PFS appear equal despite the omission of bleomycin.


Sign in / Sign up

Export Citation Format

Share Document