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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
From the First Department of Internal Medicine,
University Hospital Cologne, and the German Hodgkin Lymphoma Study
Group.
To determine prognostic factors and treatment outcome, patients
with primary progressive Hodgkin lymphoma (HD) registered in the
database of the German Hodgkin Lymphoma Study Group (GHSG) were
analyzed retrospectively. Detailed records from randomized prospective
multicenter trials performed between 1988 and 1998 of 3807 patients
recruited in these trials were reviewed. The median age of the 206 patients available was 34 years (range, 16-71). Fifty-seven patients
(28%) in intermediate stage and 149 patients (72%) in advanced stage
developed progressive disease (PD). One hundred and fifty-three
patients (74%) were treated with salvage chemotherapy, 47 patients
(23%) with salvage radiotherapy, and 6 patients (3%) did not receive
any therapy due to rapid PD. Seventy patients (34%) were treated with
high-dose chemotherapy (HDCT) and autologous stem cell transplantation.
The 5-year freedom from second failure (FF2F) and overall survival (OS)
for all patients were 17% and 26%, respectively. The 5-year FF2F and
OS for patients treated with HDCT were 31% and 43%, respectively. In
multivariate analysis low Karnofsky performance score at the time of
progression (P < .0001), age above 50 years
(P = .019), and failure to attain a temporary remission
on first-line treatment (P = .0003) were significant
adverse prognostic factors for OS. Patients with none of these risk
factors had a 5-year OS of 55% compared with 0% for patients with all
3 of these unfavorable prognostic factors. Although HDCT is a
reasonable option for selected patients with primary progressive HD,
the majority did not receive HDCT. Interestingly, salvage radiotherapy
gave promising results in patients with localized PD.
(Blood. 2000;96:1280-1286) The majority of patients with Hodgkin lymphoma (HD)
can be cured with conventional chemotherapy or radiotherapy or
both.1 However, the outcome of patients with primary
progressive disease (PD) defined as progression during induction
treatment or within 90 days after the end of treatment is dismal.
Treatment results with second-line chemotherapy produces low
remission rates, with long-term disease-free survival (DFS) in 0% to
10% of patients with primary progressive HD.2,3 Salvage
radiotherapy is an effective treatment for localized relapsed HD, but
little is known about radiotherapy in patients with PD. Experiences
with high-dose chemotherapy (HDCT) followed by autologous stem cell
transplantation (ASCT) from selected series in primary progressive HD
indicate a DFS rate of 31% to 42%.4-7 However, patients
receiving HDCT undergo a considerable selection. A high proportion of
patients are not treated with HDCT because of rapid disease
progression, insufficient stem cell harvest, poor performance status,
or older age.
We thus retrospectively analyzed patients with primary progressive HD
after first-line polychemotherapy who are registered in the database of
the German Hodgkin Lymphoma Study Group (GHSG). Patient
characteristics, salvage treatment, and prognostic factors were
evaluated at the time of progression. The purpose of the present
analysis is to assess whether and to which extent long-term DFS can be
achieved in patients with primary progressive HD and to determine
patient-, disease-, and treatment-related factors correlated with outcome.
Patient selection
Salvage therapy
Staging procedures after salvage treatment Before salvage therapy, the extent of disease was assessed by chest x-ray, abdominal sonography, computed tomography, and bone marrow biopsy. Restaging was performed after salvage chemotherapy or radiotherapy. After the end of the salvage therapy and prior to ASCT, all sites of initial disease were reassessed by adequate methods including bone marrow biopsy for patients who had bone marrow involvement before salvage therapy.Response definition A CR was defined as the disappearance of all clinical and radiographic evidence of disease for at least 1 month. PR was defined as a greater than 50% reduction in the product of the largest diameter and its perpendicular of measurable disease lasting more than 1 month. Any response less than PR was considered a treatment failure.Statistics Freedom from second treatment failure (FF2F) was measured from the date of entry into the salvage protocol until progression, relapse, or death from any cause. Overall survival (OS) was measured from the date of entry into the salvage protocol until death from any cause. Demographics and disease characteristics were summarized using descriptive statistics. OS and FF2F rates were estimated according to the method of Kaplan and Meier.11 The prognostic significance of various factors was tested by multivariate Cox regression analysis for each of the outcome variables (FF2F and OS).12 All patients who received salvage therapy with curative intent were included.The factors tested were as follows:
In the main analysis, only factors available at (or before) progression were included. Sensitivity to conventional salvage chemotherapy was included only after assessing the significance of the above factors. Candidate factors were examined by stepwise procedures: removal
and entry levels of significance were 0.1 and 0.05, respectively. All
P values are 2-sided. Due to the presence of multiple
comparisons (10 factors were tested), significance should be finally
assessed, following Bonferroni,13 using the more stringent
threshold P value of .05/10 = .005. Once the selection of
factors had been made, each selected factor was simplified into 2 categories (age
Patient characteristics A total of 239 patients with primary progressive HD were identified. Patients were excluded from the final analysis due to non-Hodgkin lymphoma (NHL) histology at PD (n = 12), insufficient first-line therapy (n = 6), refusal of salvage therapy (n = 8), palliative radiotherapy (defined as radiation not delivered to all involved sites; n = 6), and lack of data on salvage therapy (n = 1). Thus, 206 patients were available for the final analysis. Patient characteristics are listed in Table 2.
The median age of the patients at progression was 34 years (range, 16-71 years). There were 112 males (54%) and 94 females (46%) with the following histologies at first diagnosis: nodular sclerosis, 140 (68%); mixed cellularity, 46 (22%); lymphocyte depleted, 11 (5%); lymphocyte predominant, 5 (3%); and unclassified, 4 patients (2%). Progression was proven by biopsy in 118 patients (57%) or demonstrated unequivocally on radiographic studies. Fifty-seven patients (28%) had intermediate stage and 149 patients (72%) advanced stage at first diagnosis. In 148 patients (72%), a remission (PR or CR) had been documented during staging examinations after 4 or 8 cycles of first-line chemotherapy. Stage at progression by Ann Arbor criteria was stage I in 24 patients (11%), stage II in 64 (31%), stage III in 37 (18%), and stage IV in 81 patients (40%). Twenty-one patients (10%) had extranodal disease, 21 (10%) had bone involvement, 28 (14%) had liver involvement, 45 (22%) had lung involvement, and 7 (3%) had bone marrow involvement. Twenty-three patients (11%) had more than one organ involvement. Forty-eight patients (23%) had Karnofsky performance scores less than 90, and 97 patients (47%) had B symptoms at the time of progression. Initially, 111 patients (54%) had been treated with COPP/ABVD at initial diagnosis, 57 patients (28%) with COPP/ABV/IMEP, and 38 patients (18%) with BEACOPP (15% BEACOPP baseline; 3% BEACOPP escalated). Eighty-one patients (37%) had received both chemotherapy and radiotherapy during first-line treatment. Time until progression and localization of disease progression Disease progression occurred after a median of 7 months after first diagnosis; 143 (70%) patients had disease progression during first-line treatment. Twenty patients (9%) had progressive disease within the first month, 27 patients (13%) within the second month, and 16 patients (8%) within the third month after the end of first-line treatment. PD occurred in initial areas in 91 patients (44%), in initial areas and new areas in 97 patients (47%), and only in new areas in 15 patients (7%). Data on disease localization were missing in 3 patients (2%).Salvage treatment After documented progress, 153 patients (72%) received second-line chemotherapy. Forty-seven patients (22%) were treated with salvage radiotherapy with intent to cure, defined as radiation delivered to all involved sites. Another 6 patients (3%) did not receive any therapy due to rapid progressive disease and died 1 to 8 months after first diagnosis. Seventy-eight patients (51%) received Dexa-BEAM as salvage chemotherapy (dexamethasone, carmustine, etoposide, cytarabine, melphalan), 15 patients (10%) CEVD (cyclophosphamide, etoposide, vindesine, dexamethasone). Several other second-line salvage chemotherapy regimens were used, mostly based on etoposide, ifosfamide, ciplatin, or high-dose Ara-C such as IMVP-16 (ifosfamide, methotrexate, etoposide), IEV (ifosfamide, epirubicin, etoposide), and DHAP (dexamethasone, cytarabine, cisplatin). Fifty patients (33%) treated with salvage chemotherapy had stage I/II and 103 (67%) had stage III/IV at the time of disease progression. The overall response rate after salvage chemotherapy was 43% (37% CR and 6% PR). Salvage radiotherapy as second-line treatment with curative intention included TNI in 9 patients, EF radiotherapy in 15 patients, MF radiotherapy in 14 patients, and IF radiotherapy in 9 patients. The median dose of radiotherapy delivered was 40 Gy (range, 30.6-50 Gy). Thirty-eight patients (81%) treated with salvage radiotherapy had stage I/II, 8 patients (17%) stage III, and 1 patient stage IV at the time of disease progression. Eleven patients (23%) had B symptoms, 7 (15%) had a Karnofsky status below 80, and 7 (15%) were over 50 years old. The overall response rate after salvage radiotherapy was 66% (62% CR and 4% PR).High-dose chemotherapy and stem cell transplantation Seventy patients (33%) were treated with HDCT and ASCT. Of those, 62 patients received HDCT after CR or PR on conventional salvage therapy and 8 patients were treated with HDCT in chemoresistant progression. Twelve of these 70 patients had relapsed after radiotherapy as initial salvage treatment and 58 patients had initially been treated with salvage chemotherapy. The source of stem cells was bone marrow in 21% and peripheral blood in 79% of the cases. Nine patients received radiotherapy to residual lymphoma after HDCT. The HDCT regimens used were BEAM in 38 patients (54%) (carmustine [BCNU], etoposide, cytarabine, and melphalan) and CVB in 22 patients (31%) (cyclophosphamide, etoposide, and carmustine [BCNU]). Two patients (3%) received a total body irradiation-containing regimen, and 8 patients (12%) were treated with other regimens (Table 2).The majority of patients receiving salvage chemotherapy were excluded from high-dose programs because of progressive disease on salvage chemotherapy (60%), life-threatening severe toxicity on salvage treatment (11%), insufficient stem cell harvest (1%), or age above 60 years (1%). Survival With a median observation time of 52 months, the actuarial 5-years FF2F and OS for all patients after initiation of salvage therapy were 17% and 26%, respectively (Figure 1). Currently, 77 patients are alive with a follow-up between 3 and 110 months. Among those who did not survive, 112 patients (53%) died as a result of disease progression, 19 patients (9%) died due to life-threatening severe toxicity on salvage treatment; 3 patients (1%) died from secondary acute myelogenous leukemia or myelodysplastic syndrome, and 1 patient (< 1%) died after myocardial infarction.
The actuarial FF2F and OS for 70 patients treated with HDCT and ASCT
were 31% and 43%, respectively (Figure
2). Sixty-two patients (89%) treated
with HDCT had reached a remission (PR/CR) with conventional salvage
therapy before HDCT. Of 8 patients treated with HDCT in chemoresistant
disease, 3 are alive and in continuous CR 6 to 61 months after HDCT.
Although the use of HDCT for patients with primary progressive HD
increased from 1988 to 1998, less than 50% of all cases underwent
transplantation even in the late 1990s (Figure
3).
For patients treated with salvage radiotherapy, FF2F and OS after 4 years were 22% and 52%, respectively (Figure
4). Currently, 11 patients (23%) are
alive and in continuous CR after salvage radiotherapy with a median of
34 months follow-up (range, 6-79 months). Twenty-five patients (54%)
who relapsed (18 patients) or who were refractory (7 patients) to
salvage radiotherapy were treated with a salvage chemotherapy regimen.
Of those, 12 patients received HDCT and ASCT. Among these patients, 7 are alive and in continuous CR.
Prognostic factors The results from the univariate analysis are listed in Table 3. In multivariate analysis, chemosensitive disease on salvage chemotherapy (P < .0001), Karnofsky performance score at the time of progression (P < .0001), age (P = .0026), and attainment of a temporary remission before progression (P = .0034) were significant prognostic factors for OS (Table 4). Backward and forward selection procedures both identified identical significant factors. As shown in Figure 5, the most predictive factor was the Karnofsky performance score. Patients with Karnofsky performance scores of 90 or above had an OS of 34%, whereas patients with Karnofsky scores less than 90 had an OS of 6%. Age was also an important prognostic factor, with 4-year survival of 35% for patients under 30 years but virtually no chance of even 2-year survival for patients older than 50 years (Figure 6). Patients achieving remission before first progression had an 18% higher survival probability than the remainder (Figure 7). For FF2F, only the Karnofsky performance score was consistently significant (P = .0046). OS for patients progressing after intermediate or advanced stage at first diagnosis did not show any difference (P = .15).
The factors Karnofsky performance score, age, and previous remission
were each dichotomized into 2 categories: Karnofsky performance score
of 90 or above or less than 90, age 50 years or less or more than 50 years, with or without previous remission. Table 5 shows the model predictions for 3-year
OS rates for each combination of factor categories. These predictions
are compared with the Kaplan-Meier estimates for the respective
patients group for all combinations with at least 10 cases. For
patients over 50 years the numbers of cases with each of the 4 combinations was too small; when pooled, these 22 older patients had a
Kaplan-Meier estimate of only 4% OS at 3 years. The results are valid
in the context of the treatment strategies actually chosen for these
progressing patients. Obviously, choice and administration of treatment
may play an important role alongside prognostic factors.
Several important findings emerge from this analysis. (1) The clinical outcome for patients registered in the GHSG database with primary progressive HD is poor. The 5-year FF2F is 17% and the 5-year OS is 26% for a total of 206 patients evaluable. (2) Prognostic factors for OS being predictive at the time of disease progression include Karnofsky performance score, age, and achievement of a temporary remission with first-line treatment. Patients with none of these risk factors had a predicted 3-year OS of 55% compared with 0% for patients with 3 of these unfavorable prognostic factors. (3) Salvage radiotherapy can give promising results in a subset of patients with localized PD. One of the most adverse prognostic factors in HD is primary disease progression to an initial chemotherapy regimen. Patients with primary PD have a particular poor response to second- or third-line induction treatment. Their probability of long-term survival with conventional chemotherapy is low. The 5-year OS ranges between 0% and 10% in small series reported.2,3 In an attempt to improve the outcome for patients with primary progressive HD, HDCT followed by ASCT has been increasingly used.4-7 We retrospectively analyzed Hodgkin lymphoma patients with PD registered in the GHSG database to determine prognostic factors and outcome after salvage treatment. Another aim of this study was to identify patients who are candidates for more aggressive treatment modalities. The collection of data was based on the definition of primary progressive disease as disease progression during induction treatment or within 90 days after the end of treatment.2,6,7,14 Our results show that the long-term outcome of patients with primary progressive HD is disappointing. The 5-year FF2F and OS rates for all patients were 17% and 26%, respectively. This predominantly poor prognosis emphasizes the need for more effective first-line treatments that reduce primary progression rates.10 The 5-year OS of patients progressing after presenting in intermediate or advanced stages at first diagnosis did not differ significantly, indicating that one of the most important determinants of outcome in primary treatment is less important when disease progression occurs. An important predictive factor correlated with OS was the Karnofsky performance score at the time of disease progression. The 5-year probability of OS with Karnofsky performance scores of 90% or higher and less than 90% were 34% and 6%, respectively. The age of the patient was also an important factor for OS. Unfortunately, older age and poor performance status may discourage the use of more aggressive treatment modalities in these patients. Moreover, attainment of a temporary remission with first-line chemotherapy was a significant predictor for OS. Patients never achieving a temporary remission during first-line chemotherapy had an 18% lower survival probability than the remainder, indicating the biologic aggressiveness of the disease in this subgroup. The model predictions for each combination of factor categories show that the predicted 3-year OS for patients with none of these risk factors was 55% compared with 0% for patients with 3 of these unfavorable prognostic factors. Therefore, for patients presenting with reduced Karnofsky performance score, age 50 years or older, and with no temporary remission on first-line therapy, palliative rather than aggressive treatment modalities should be used. The results of HDCT/ASCT in primary progressive HD reported from selected series are promising, with 5-year failure-free and overall survival (progression-free survival [PFS]) of 31% to 42%, respectively.4-7 More recent studies reported improved outcome after HDCT/ASCT for refractory HD when compared with historical controls treated with conventional chemotherapy.15,16 Thus, HDCT is clearly an effective treatment for these patients. However, patients receiving HDCT undergo a selection bias. A proportion of patients are not included in HDCT programs because of rapid disease progression, older age, poor performance status, or insufficient stem cell harvest. Furthermore, the comparison is biased because the administration of HDCT occurred during the follow-up period. The presence of bias in OS is evident when we consider that some patients failed to receive HDCT simply because they died early. To avoid bias, a multivariate analysis was performed using the landmark method.14 Patients receiving HDCT within 6 months of progression were compared with those not receiving HDCT within this period; patients surviving less than 6 months were excluded. Allowing for relevant patient characteristics and for chemosensitivity in salvage therapy, the course of the HDCT group was not significantly better than that of the other group (P = .091). Therefore, the particularly good results of the HCDT patients may be due to patient selection and to the above-mentioned bias; we cannot conclude that treatment with HDCT has improved the results. As noted in several other series, chemosensitivity to conventional salvage chemotherapy was also a significant prognostic factor in our analysis.5,17 Patients who achieve a second PR or CR to conventional salvage chemotherapy are expected to be in a favorable position to proceed to HDCT.17,18 Nevertheless, the role of conventional salvage chemotherapy before HDCT has not been clearly defined. It has been used in the past for chemosensitivity testing and has been given for several cycles to induce tumor regression, often while logistic arrangements are underway for HDCT.19 Chopra and coworkers established the effectiveness of HDCT in producing long-term PFS even in patients failing an aggressive pretransplant salvage treatment.5 Several other studies have confirmed that some patients with disease resistant to conventional therapy may benefit from HDCT, but long-term survival or PFS rates (or both) in such patients are low, ranging from 10% to 30%.5,13,14,20 However, as recently reported by our group, a substantial proportion of chemoresistant patients are not included in HDCT programs.21 In this present analysis, only 34% of all patients received HDCT. The relatively low rate of using HDCT can only in part be explained by the infrequent use of HDCT during the first years of our observation period starting in 1988 or chemoresistance to conventional salvage chemotherapy as an exclusion criteria from HDCT programs. Although the use of HDCT for patients with primary progressive HD increased from 1988 to 1998, less than 50% of all cases were treated with HDCT in the late 1990s. In our analysis, a high proportion of chemoresistant patients rapidly succumb to progressive disease. Thirty-one percent of the patients not receiving HDCT had rapidly progressive disease and died within 1 to 6 months after disease progression. Life-threatening severe toxicity on salvage treatment occurred in 11% of the patients. Insufficient stem cell harvest, poor performance status, and older age had also contributed to ineligibility for HDCT. Moreover, the subgroup of patients never achieving temporary remission with front-line chemotherapy had very often rapid disease progression. Salvage radiotherapy is a valid treatment alternative in patients who have not been given radiation previously or with relapse outside the initial radiation field. In the present analysis, patients treated with salvage radiotherapy were similar regarding age and Karnofsky status to those receiving chemotherapy, but they more often had early stage progressive disease without B symptoms. The potential increase of pulmonary morbidity associated with mediastinal radiotherapy before HDCT limits the use of radiotherapy as a cytoreductive treatment prior to HDCT.22 Salvage radiotherapy offers a potentially curative option with low morbidity for a subset of selected patients. This approach has been reported in several series mostly for relapsed patients.22-25 Wirth and colleagues reported the experience of salvage radiotherapy in 51 patients with relapsed and refractory HD of whom 18 had a PR and only 4 had PD.24 Five-year failure-free survival (FFS) and OS were 26% and 57%, respectively. In view of the surprisingly good results observed in our study, radiotherapy might be used more frequently as salvage therapy for primary progressive HD. Due to the high percentage (70%) of patients who developed disease progression during first-line treatment, only a minority of patients had received prior radiotherapy. In present studies of first-line treatment of HD, radiotherapy is incorporated less frequently and with lower dosages. Therefore, incorporating salvage radiotherapy in salvage treatment programs seems to be feasible in this group of patients in future trials. Moreover, for patients with localized HD radiotherapy might be a curative treatment approach even for patients with poor performance status or older age or both. Our results show that HDCT is an effective treatment for selected patients with primary progressive HD. Prognostic factors evaluated at the time of disease progression might help to identify patients for whom either aggressive or palliative treatment strategies should be used.
Submitted November 3, 1999; accepted April 24, 2000.
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Andreas Josting, First Department of Internal Medicine, University Hospital Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany.
1. Canellos GP, Anderson JR, Propert KJ, et al. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992;327:1478[Abstract]. 2. Longo DL, Duffey PL, Young RC, et al. Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure. J Clin Oncol. 1992;10:210[Abstract].
3.
Bonfante V, Santoro A, Viviani S, et al.
Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD.
J Clin Oncol.
1997;15:528
4.
Horning SJ, Chao NJ, Negrin RS, et al.
High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: analysis of the Stanford University results and prognostic indices.
Blood.
1991;89:801
5.
Chopra R, McMillan AK, Linch DC, et al.
The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease: a single center eight year study of 155 patients.
Blood.
1993;81:1137 6. Sweetenham JW, Taghipou G, Linch DC, Goldstone AH. Thirty percent of adult patients with primary refractory Hodgkin's disease are progressive free at 5 years after high-dose therapy and autologous stem cell transplantation: data from 290 patients reported to the EBMT. Blood. 1996;(suppl 1)88:486a.
7.
Lazarus HM, Rowlings PA, Zhang MJ, et al.
Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.
J Clin Oncol.
1999;17:534 8. Sieber M, Rueffer U, Tesch H, et al. Rapidly alternating COPP + ABV + IMEP (CAI) is equally effective as alternating COPP + ABVD (CA) for Hodgkin's disease: final results of two randomized trials for intermediate (HD5 protocol) and advanced (HD6 protocol) stages. Blood. 1997;90:586a. 9. Rueffer U, Sieber M, Pfistner B, et al. Reduction of radiotherapy volume in intermediate Hodgkin's disease: interim analysis of a randomized trial in patients CS I/II of the GHSG. Blood. 1998;92:2580a.
10.
Diehl V, Franklin J, Hasenclever D, et al.
BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group.
J Clin Oncol.
1998;16:3810 11. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457. 12. Cox DR. Regression models and life tables. Stat Soc. 1972;34:187.
13.
Yuen AR, Rosenberg SA, Hoppe RT, Halpern JD, Horning SJ.
Comparison between conventional salvage chemotherapy and high-dose therapy with autografting for recurrent and refractory Hodgkin's disease.
Blood.
1997;89:814 14. Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol. 1983;1:710[Abstract].
15.
Andrè M, Henry-Amar M, Pico JL, et al.
Comparison of high-dose therapy and autologous stem-cell transplantation with conventional therapy for Hodgkin's disease induction failure: a case-control study.
J Clin Oncol.
1999;17:222
16.
Reece DE, Barnett MJ, Shepherd JD, et al.
High-dose cyclophosphamide, carmustine, and etoposide with or without cisplatin and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy.
Blood.
1995;86:451
17.
Rapoport AP, Rowe JM, Kouides PA, et al.
One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome.
J Clin Oncol.
1993;11:2351
18.
Josting A, Kátay I, Rueffer U, et al.
Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dexa-BEAM).
Ann Oncol.
1998;9:289 19. Crump M, Smith AM, Brandwein J, et al. High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant. J Clin Oncol. 1993;11:704[Abstract]. 20. Brice P, Bouaddallah R, Moreau P, et al. Prognostic factors for survival after high-dose therapy and autologous stem transplantation for patients with relapsing Hodgkin's disease: analysis of 280 patients from the French registry. Bone Marrow Transplant. 1997;20:21[Medline] [Order article via Infotrieve].
21.
Josting A, Reiser M, Rueffer U, Salzberger B, Diehl V, Engert A.
Treatment of primary progressive Hodgkin's and aggressive non-Hodgkin's lymphoma 22. Leigh BR, Fox KA, Mack CF, Baier M, Miller TP, Cassady JR. Radiation therapy salvage of Hodgkin's disease following chemotherapy failure. Int J Radiat Oncol Biol Phys. 1993;27:855[Medline] [Order article via Infotrieve].
23.
Yahalom J, Gulati SC, Toia M, et al.
Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.
J Clin Oncol.
1993;11:1062 24. Wirth A, Corry J, Laidlaw C, Matthews J, Liew KH. Salvage radiotherapy for Hodgkin's disease following chemotherapy failure. Int J Radiat Oncol Biol Phys. 1997;39:599[Medline] [Order article via Infotrieve].
25.
Brada M, Eeles R, Ashley S, Nichols J, Horwich A.
Salvage radiotherapy in recurrent Hodgkin's disease.
Ann Oncol.
1992;3:131
© 2000 by The American Society of Hematology.
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  F. Morschhauser, P. Brice, C. Ferme, M. Divine, G. Salles, R. Bouabdallah, C. Sebban, L. Voillat, O. Casasnovas, A. Stamatoullas, et al. Risk-Adapted Salvage Treatment With Single or Tandem Autologous Stem-Cell Transplantation for First Relapse/Refractory Hodgkin's Lymphoma: Results of the Prospective Multicenter H96 Trial by the GELA/SFGM Study Group J. Clin. Oncol., December 20, 2008; 26(36): 5980 - 5987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sirohi, D. Cunningham, R. Powles, F. Murphy, T. Arkenau, A. Norman, J. Oates, A. Wotherspoon, and A. Horwich Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma Ann. Onc., July 1, 2008; 19(7): 1312 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sureda, S. Robinson, C. Canals, A. M. Carella, M. A. Boogaerts, D. Caballero, A. E. Hunter, L. Kanz, S. Slavin, J. J. Cornelissen, et al. Reduced-Intensity Conditioning Compared With Conventional Allogeneic Stem-Cell Transplantation in Relapsed or Refractory Hodgkin's Lymphoma: An Analysis From the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation J. Clin. Oncol., January 20, 2008; 26(3): 455 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Schmitz, P. Dreger, B. Glass, and A. Sureda Allogeneic transplantation in lymphoma: current status Haematologica, November 1, 2007; 92(11): 1533 - 1548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Santoro, M. Magagnoli, M. Spina, G. Pinotti, L. Siracusano, M. Michieli, A. Nozza, B. Sarina, E. Morenghi, L. Castagna, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma Haematologica, January 1, 2007; 92(1): 35 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Ansell and J. O. Armitage Management of Hodgkin Lymphoma Mayo Clin. Proc., March 1, 2006; 81(3): 419 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Schellong, W. Dorffel, A. Claviez, D. Korholz, G. Mann, H.-G. Scheel-Walter, J. P.M. Bokkerink, M. Riepenhausen, H. Luders, R. Potter, et al. Salvage Therapy of Progressive and Recurrent Hodgkin's Disease: Results From a Multicenter Study of the Pediatric DAL/GPOH-HD Study Group J. Clin. Oncol., September 1, 2005; 23(25): 6181 - 6189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Josting, L. Nogova, J. Franklin, J.-P. Glossmann, H. T. Eich, M. Sieber, T. Schober, H.-D. Boettcher, U. Schulz, R.-P. Muller, et al. Salvage Radiotherapy in Patients With Relapsed and Refractory Hodgkin's Lymphoma: A Retrospective Analysis From the German Hodgkin Lymphoma Study Group J. Clin. Oncol., March 1, 2005; 23(7): 1522 - 1529. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Josting, C. Rudolph, M. Mapara, J.-P. Glossmann, M. Sienawski, M. Sieber, H. H. Kirchner, B. Dorken, D. K. Hossfeld, J. Kisro, et al. Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG) Ann. Onc., January 1, 2005; 16(1): 116 - 123. [Abstract] [Full Text] [PDF]
|
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|
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 N. L. Bartlett Therapies for Relapsed Hodgkin Lymphoma: Transplant and Non-Transplant Approaches Including Immunotherapy Hematology, January 1, 2005; 2005(1): 245 - 251. [Abstract] [Full Text] [PDF]
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J. Czyz, R. Dziadziuszko, W. Knopinska-Postuszuy, A. Hellmann, L. Kachel, J. Holowiecki, J. Gozdzik, J. Hansz, A. Avigdor, A. Nagler, et al. Outcome and prognostic factors in advanced Hodgkin's disease treated with high-dose chemotherapy and autologous stem cell transplantation: a study of 341 patients Ann. Onc., August 1, 2004; 15(8): 1222 - 1230. [Abstract] [Full Text] [PDF]
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M. Bendandi, S. A. Pileri, and P. L. Zinzani Challenging paradigms in lymphoma treatment Ann. Onc., May 1, 2004; 15(5): 703 - 711. [Full Text] [PDF]
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A. Josting, C. Rudolph, M. Reiser, M. Mapara, M. Sieber, H. H. Kirchner, B. Dorken, D. K. Hossfeld, V. Diehl, and A. Engert Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease Ann. Onc., October 1, 2002; 13(10): 1628 - 1635. [Abstract] [Full Text] [PDF]
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C. Ferme, N. Mounier, M. Divine, P. Brice, A. Stamatoullas, O. Reman, L. Voillat, J. Jaubert, P. Lederlin, P. Colin, et al. Intensive Salvage Therapy With High-Dose Chemotherapy for Patients With Advanced Hodgkin's Disease in Relapse or Failure After Initial Chemotherapy: Results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial J. Clin. Oncol., January 15, 2002; 20(2): 467 - 475. [Abstract] [Full Text] [PDF]
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A. Josting, J. Franklin, M. May, P. Koch, M. K. Beykirch, J. Heinz, C. Rudolph, V. Diehl, and A. Engert New Prognostic Score Based on Treatment Outcome of Patients With Relapsed Hodgkin's Lymphoma Registered in the Database of the German Hodgkin's Lymphoma Study Group J. Clin. Oncol., January 1, 2002; 20(1): 221 - 230. [Abstract] [Full Text] [PDF]
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U. Rueffer, A. Josting, J. Franklin, M. May, M. Sieber, K. Breuer, A. Engert, and V. Diehl Non-Hodgkin's Lymphoma After Primary Hodgkin's Disease in the German Hodgkin's Lymphoma Study Group: Incidence, Treatment, and Prognosis J. Clin. Oncol., April 1, 2001; 19(7): 2026 - 2032. [Abstract] [Full Text] [PDF]
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Top
Abstract
Introduction
90 days) after induction
treatment. Criteria for progressive disease were at least one of: (1)
25% or more increase from nadir in the sum of the products of the
greatest diameter of any previously identified abnormal node for
partial responders or nonresponders or (2) appearance of any new lesion during or less than 90 days after the end of therapy. A rebiopsy at the
time of disease progression was recommended. This analysis is based on
data extracted from the database and patient files between February and
April 1999.
50 or < 50 years, Karnofsky performance score
is there a chance for cure?
J Clin Oncol.
2000;18:332