Is There a Role for Autologous Stem-Cell Transplantation (ASCT) in Peripheral T-Cell Lymphoma (PTCL)? Final Results of a Prospective Phase II Study from the GELCAB.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3070-3070 ◽  
Author(s):  
Santiago Mercadal ◽  
Armando Lopez-Guillermo ◽  
Javier Briones ◽  
Blanca Xicoy ◽  
Carme Pedro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Stage Iv ◽  
Severe Infection ◽  
High Dose Chemotherapy ◽  
Hematological Toxicity ◽  
High Dose ◽  
Cell Mobilization

Abstract The outcome of patients (pts) with PTCL receiving conventional therapy is dismal. Because of this, there is an increasing interest to investigate intensive treatments in these patients. The aim of this study was to analyze the toxicity, response and outcome of a phase II trial that includes high-dose chemotherapy (CT) plus ASCT as first-line treatment for pts with PTCL. Forty-one pts (30M/11F; median age: 47 yrs.) diagnosed with PTCL (excluding cutaneous and anaplastic ALK+), in stages II-IV and <65 years were the subject of this analysis. Twelve pts (29%) presented with primary extranodal disease, 29 (71%) were in stage IV, and 14 (35%) had bone marrow involvement. Forty-six percent of the pts had high/intermediate or high-risk IPI, whereas 49% were in the groups 3 or 4 according to the Italian Index for PTCL. Pts received intensive CT (3 courses of high-dose CHOP [cyclophosphamide 2000 mg/m2 day 1, adriamycin 90 mg/m2 day 1, vincristine 2 mg day 1, prednisone 60 mg/m2/day, days 1 to 5, mesnum 150% of cyclophosphamide dose, G-CSF 300 mg/day days 7 to 14], alternating with 3 courses of standard ESHAP). Responders (CR or PR) were submitted to ASCT. Median follow-up of surviving pts was 3.2 years (range, 0.6–8.1). Twenty-eight pts (68%) received the planned 6 courses of CT. Response rate after CT was as follows: CR, 20 cases (49%); PR, 4 (10%); failure, 17 (41%), including one pt who died because of sepsis. Hematological toxicity of CT mainly consisted of neutropenia (median nadir after high-dose CHOP and ESHAP: 0.01 and 0.4x109/L, respectively) and thrombocytopenia (23 and 29x109/L, respectively). Severe infection requiring hospitalization was observed in 38 and 15% of courses of high-dose CHOP or ESHAP, respectively. Only 17 of the 24 candidates (41% of all pts) received ASCT due to the lack of stem-cell mobilization (3 cases), severe previous toxicity (2), early relapse of the lymphoma (1) and pt decision (1). No major toxicity was observed after ASCT. The overall response after the whole treatment was: CR, 21 cases (51%), PR, 3 (7%), failure, 17 (42%). Four-year failure-free survival (FFS) was 30% (95%CI: 14–46%), whereas 4-year EFS was 51% (95%CI: 29–73%). Twenty-two pts have died during follow-up, with a 4-yr OS of 39% (95%CI: 22–56%). Notably, no significant differences in the outcome were seen among the 24 pts candidates for ASCT according to whether or not they eventually underwent this procedure. Four of 17 transplanted and 4 of 7 nontransplanted pts eventually relapsed. In addition, 2 pts died in CR after ASCT due to the development of a Burkitt-like lymphoma and lung cancer at 18 and 5 months from the procedure. Thus, 4-year EFS was 59% (95%CI: 33–85%) and 29% (95%CI 0–73%) for transplanted and nontransplanted pts, respectively (p>0.1). Four-year OS was 57% (95%CI: 31–83%) and 71% (95%CI: 37–100%), respectively (p>0.1). In summary, in this series of patients with PTCL a relatively high CR rate was obtained with high-dose CHOP/ESHAP followed by ASCT. Toxicity was manageable. The contribution of ASCT to pts outcome is debatable because of the absence of significant differences in OS and EFS of patients in CR transplanted vs. those not transplanted. Novel strategies aimed at increasing the CR rate in these patients warrant investigation.

Intensive Chemotherapy (High-Dose CHOP/ESHAP Regimen) Followed by Autologous Stem-Cell Transplantation (ASCT) in Previously Untreated Patients with Peripheral T-Cell Lymphoma (PTCL). Results of a Prospective Phase II Study from the GELCAB.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2077-2077 ◽  
Author(s):  
Armando Lopez-Guillermo ◽  
Santiago Mercadal ◽  
Javier Briones ◽  
Blanca Xicoy ◽  
Carme Pedro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Disease Free Survival ◽  
Severe Infection ◽  
Hematological Toxicity ◽  
High Dose ◽  
Free Survival

Abstract The outcome of patients (pts) with PTCL receiving conventional therapy is dismal. Because of this, there is an increasing interest to investigate intensive treatments in these pts. The aim of the study is to analyze the interim results, in terms of toxicity, response and outcome, of a phase II trial that includes high-dose chemotherapy (CT) plus ASCT as 1st-line treatment for pts with PTCL. Thirty-four pts (23M/11F; median age: 47 yrs.) diagnosed with PTCL (excluding cutaneous and anaplastic ALK+), in stages II–IV and ≤65 yrs, who have already finished planned therapy, are the subject of this analysis. Nine pts (26%) presented with primary extranodal disease, 24 (71%) were in stage IV, and 13 (38%) had bone marrow involvement. Fifty percent of the pts had high/intermediate or high-risk IPI, whereas 53% were in the groups 3 or 4 according to the Italian Index for PTCL. Pts received intensive CT (3 courses of high-dose CHOP [cyclophosphamide 2000 mg/m2 day 1, adriamycin 90 mg/m2 day 1, vincristine 2 mg day 1, prednisone 60 mg/m2/day, days 1 to 5, with mesnum and G-CSF], alternating with 3 courses of standard ESHAP). Responders (CR or PR) were submitted to ASCT. Median follow-up of surviving pts was 3.9 yrs (range, 0.5–7.6). Twenty four pts (71%) received the planned 6 courses of CT. Response rate after CT was: CR, 12 cases (35%); PR, 8 (23%); failure, 14 (42%), including one pt who died because of sepsis. Hematological toxicity of CT mainly consisted of neutropenia (grades 3–4 in 87 and 62% after high-dose CHOP and ESHAP, respectively) and thrombocytopenia (grades 3–4 in 63 and 68%, respectively). Severe infection requiring hospitalization was observed in 38 and 15% of courses of high-dose CHOP or ESHAP, respectively. Only 14 of the 20 candidates (70% of all candidates and 41% of all pts) received ASCT due to lack of stem-cell mobilization (3 cases), previous toxicity (2) and pt decision (1). No differences in the outcome were seen among these 20 pts according to whether or not they could eventually receive ASCT. No major toxicity was observed after ASCT. The overall response after the whole treatment was: CR, 14 cases (41%), PR, 5 (15%), failure, 15 (44%). Two of 14 pts in CR and the 5 pts in PR eventually progressed. Four-year failure-free survival (FFS) was 30%, whereas 4-year disease-free survival for pts achieving CR was 63%. Nineteen pts have died during follow-up, with a 4-yr overall survival (OS) of 38% (95%CI: 21–55%). Most patients died because of PTCL progression, but 2 pts died in CR due to a secondary acute lymphoblastic leukemia and to a lung cancer, respectively. IPI and Italian Index for PTCL were able to predict FFS and OS. In summary, in this series of patients with PTCL a relatively high CR rate was obtained with high-dose CHOP/ESHAP followed by ASCT. Toxicity was manageable. However, the prognosis of patients with PTCL, particularly of those not achieving CR, is still very unfavorable. Figure Figure

The Utility of Consolidative Upfront High Dose Chemoradiotherapy and ASCT in Patients with Mantle Cell Lymphoma (MCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2072-2072
Author(s):  
Daniel Persky ◽  
Carol S. Portlock ◽  
Simone Lessac-Chenen ◽  
Alexia Iasonos ◽  
Andrew D. Zelenetz ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Significant Difference ◽  
Dose Dense

Abstract Introduction: Two approaches to improve progression-free survival (PFS) in MCL are intensifying induction, as with hyperCVAD/M-A regimen, or intensifying consolidation with high dose chemoradiotherapy (HDT) and ASCT as in the prospective European MCL Network Trial. At MSKCC the strategy is to incorporate both approaches by administering an anthracycline-containing regimen in a dose dense fashion (CHOP- or R-CHOP-14) followed by consolidation with ICE (ifosfamide, carboplatin, etoposide) and HDT/ASCT. Patients: Forty six patients with newly diagnosed MCL underwent HDT/ASCT between 11/96 and 2/05. The median age was 55 years; 74% were male; 72% had bone marrow involvement, 39% had GI involvement, 7% were in leukemic phase, and 91% presented with stage IV disease. Splenomegaly was seen in 35%, B symptoms in 9%, KPS>70 in 93%, elevated LDH in 23%, and blastoid histology in 9%. Results: Induction was 4 to 6 cycles of CHOP-14 (43%), R-CHOP-14 (37%), or other doxorubicin-containing regimen (20%). Consolidation was performed with 2–3 cycles of ICE in 53% or R-ICE in 39%. Upfront treatment was well tolerated and permitted adequate stem cell collection and prompt transition to HDT/ASCT. Conditioning regimens were TBI/CY/VP-16 (59%) and BEAM (41%). Involved field radiation therapy was administered to 65%. Post-ASCT rituximab maintenance was given to 39%, with 57% of patients receiving rituximab as part of their treatment. Anthracycline-based induction led to CRu of 44% and ORR of 98%. Seventy two percent of patients were transplanted in CR, while the remaining 28% were in PR. At a median follow-up of 2.5 years (range 0.4–8.0 years) 17% of the patients have died and 24% have had progressive disease. The median OS and PFS have not been reached (lower 95% CI, 5.7 years and 4.4 years, respectively). The 5-year PFS and OS are 58% and 83%, respectively. The use of rituximab at any point during treatment prolonged PFS - only 1 of 26 patients receiving rituximab relapsed, as compared to 10 of 20 patients who were rituximab naive (p=0.03); thus far there is no significant difference in OS. There was no day 100 treatment related mortality. One patient developed bronchiolitis obliterans after ASCT and died of pulmonary fibrosis 6.5 years later; 3 patients have died of secondary cancers - one case each of MDS (1.6 years after ASCT), melanoma and lung cancer. Conclusion: These data provide evidence that dose-dense induction with CHOP-14 or R-CHOP-14 and consolidation with ICE/HDT/ASCT appears to be safe and effective, with minimal acute toxicity. Although the median follow-up is short, the use of rituximab appears to improve PFS. This contrasts with the findings of German LGLSG and may be a consequence of in vivo rituximab purging. Future therapy could incorporate all the successful elements of prior treatment programs, including R-CHOP-14, R-ICE, and radioimmunotherapy with high dose chemotherapy conditioning regimen, followed by ASCT and rituximab-based maintenance. PFS stratified by Rituximab PFS stratified by Rituximab

High-Dose Chemotherapy and Autologous Stem-Cell Transplantation for Primary CNS Lymphoma: Updated Results from a Pilot and Phase II Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3594-3594
Author(s):  
Gerald Illerhaus ◽  
Fabian Müller ◽  
Friedrich Feuerhake ◽  
J.ürgen Finke
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Pilot Trial ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose

Abstract Introduction: High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in younger patients (pts.). A 5-year overall survival probability (OS) of 69% could be demonstrated in 30 pts within a phase-II trial on HDT and ASCT with consolidating whole-brain-irradiation (WBRT) (Illerhaus et al. JCO 2006). A subsequent pilot trial on HDT and ASCT without WBRT showed a 5-year OS of 77% (Illerhaus et al. Haematologica 2008). Here we give an update of our two different treatment regimens and future perspectives. Patients and Methods: Thirty pts. ≤65 years were treated within the phase II trial, chemotherapy (CHT) consisted of 3 cycles of high-dose methotrexate (MTX, 8 g/m2), 1 cycle of AraC (2× 3 g/m2) plus thiotepa (TT, 40 mg/m2) followed by rG-CSF and stem-cell-mobilization. Conditioning regimen included BCNU (400 mg/m2) and TT (2×5 mg/kgBW) followed by ASCT. Hyperfractionated WBRT (45 Gy, 2×1Gy/d) was administered as consolidation. In our subsequent pilot trial 13 pts. (age 38–67 years) were treated without consolidating WBRT; CHT was intensified with 4 cycles MTX 8g/m2, 2 cycles AraC (2× 3 g/m2) and TT (40 mg/m2). Dose escalated HDT included BCNU (400 mg/m2) and TT (4×5 mg/kgBW) followed by ASCT. WBRT was reserved for pts. not responding to CHT. Results: Median follow-up of the 30 pts. treated within our phase II trial was extended to 95 months (mo), the updated 5-year OS of all pts. is 66.6% and 82,3% of the subgroup of pts. who underwent HDT and ASCT (n=23), respectively. Three additional deaths occurred due to relapse (n=2) after 45 and 71 mo and due to comorbidity (n=1) after 103 mo. Five of 30 pts. developed severe leukoencephalopathy during follow-up. With a median follow-up of 35 mo in the 13 pts. treated within the pilot-phase without consolidating WBRT 3-year OS of all pts. is 77%. No further relapse or non-relapse mortality occurred in this pilot-group during. Most recent follow-up data will be presented in detail. Conclusion: Sequential systemic application of high-dose cytostatic agents followed by HDT+ASCT is highly effective as initial therapy for pts. with PCNSL. The restriction of WBRT to refractory disease shows similar OS rates and a decrease in neurotoxicity. In an ongoing multicenter phase-II trial immunotherapy with rituximab is combined with HDT and ASCT to further increase remission rates. A future randomized trial should be focused on the efficacy of consolidation with HDT supported by ASCT.

Zevalin®/BEAM/Rituximab vs BEAM/Rituximab and Autologous Stem Cell Transplantation (ASCT) for Relapsed Chemosensitive Diffuse Large B-Cell Lymphoma (DLBCL): Impact of the IPI and PET Status.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 620-620 ◽  
Author(s):  
Amin M. Alousi ◽  
Chitra Hosing ◽  
Rima M. Saliba ◽  
Rosamar B. Valverde ◽  
Farzaneh Maadani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Early Death ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
Fixed Dose ◽  
High Dose ◽  
Conditioning Regimens ◽  
Cell Mobilization ◽  
Related Mortality

Abstract Background: The addition of rituximab (R) has improved results for pts with relapsed DLBCL who undergo high-dose chemotherapy followed by ASCT (Khouri, JCO, 2005). Recently, the incorporation of radio-labeled antibodies such as Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) to conditioning regimens has been evaluated. Herein, we compare the outcome in pts treated with these 2 regimens. Methods: Pts with relapsed chemosensitive DLBCL were treated on 2 consecutive trials. Between 1999 and 2003, 53 pts were enrolled on a protocol with BEAM combined with R at 1000 mg/m2 and on days +1 and +8 after ASCT (R-BEAM). Between 2004 and 2006, 25 pts were entered onto a trial of Zevalin given at the fixed dose of 0.4 mCi/Kg on day -14 followed by BEAM (days −7 to −1) with R on days +1 and +8 after ASCT (Z-BEAM). Both groups received R during stem cell collection at a dose of 375 mg/m2 the day before chemotherapy for stem cell mobilization and at 1000 mg/m2 7 days later. There was no statistical difference in age, sex distribution, # of prior therapies between the 2 groups. LDH, PET and remission status at transplant were comparable. However, serum b2- microglobulin level was higher in R-BEAM pts [median 2.2 vs 1.9, (p=.02)] and they were also more likely to have an IPI ≥ 1: 39% vs 8% (p=0.005). Results: Median follow-up: 18 mos (range, 6–35) in Z-BEAM and 52 mos (range, 21–74) for R-BEAM. Both groups were staged with CT, PET scan and marrow biopsies, every 3 mos for a year, and then every 6 mos. OS and DFS @ 2 yrs were 92% (95% CI, 72–98) and 84% (95% CI, 62–93) for Z-BEAM vs. 83% (95%CI, 70–91) and 72% (95% CI, 57–82) for R-BEAM (P = 0.5 for both OS/DFS). Within the R-BEAM group, PET status and IPI at transplant were important prognostic factors for OS {91% vs 50% for PET (−) and (+), P = 0.004; 94% vs 67% for IPI 0 vs. ≥1, P = 0.02} and DFS. DFS of pts with IPI 0 were 86% vs 81% for Z-BEAM and R-BEAM, respectively (P = 0.9). A comparison for high IPI pts could not be done due to the small number of such pts in the Z-BEAM group. DFS for pts who were PET (+) were 75% vs 44% within the Z-BEAM and R-BEAM groups, respectively: a difference that did not reach significance due to the small number of pts (4 vs 10). Treatment-related mortality was comparable with only one early death within the Z-BEAM group due to sepsis. Results suggest a faster WBC recovery with Zevalin {ANC > 500, day +9 vs. day +11 (p<0.001)}. However, results may be confounded by the use of different cytokines. Platelet engraftment was similar in both groups. Conclusions: Fixed dose Zevalin of 0.4 mCi/kg can be added to BEAM without increasing toxicity. Z-BEAM and R-BEAM have comparable results in relapsed chemosensitive DLBCL pts with IPI 0 and PET (−) at transplant. Pts with IPI ≥ 1 and PET (+) have suboptimal results with R-BEAM. Randomized trials are needed to address whether the addition of Zevalin for these pts may improve their outcome.

scholarly journals A phase II study of high-dose cisplatin and VP-16 in neuroblastoma: a report from the Société Française d'Oncologie Pédiatrique.

1987 ◽  
Vol 5 (6) ◽  
pp. 941-950 ◽  
Author(s):  
T Philip ◽  
R Ghalie ◽  
R Pinkerton ◽  
J M Zucker ◽  
J L Bernard ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Bone Marrow Involvement ◽  
Stage Iv ◽  
Observation Time ◽  
Phase Iii ◽  
High Dose ◽  
Initial Stage ◽  
Duration Of Response

Forty-seven children or adolescents with initial stage IV (42 patients) or stage III (five) advanced neuroblastoma (12 were progressing after relapse and 35 had never reached complete remission [CR] after conventional therapy) were included in a phase II study of the combination of high-dose VP-16 (100 mg/m2/d X 5) and high-dose cisplatin (CDDP) (40 mg/m2/d X 5). Twenty patients had received prior CDDP therapy (total dose, 100 to 640 mg/m2; median, 320 mg/m2) and 38 of 47 had bone marrow involvement when included in the study. The overall response rate was 55%, with 22% CR. Duration of response was 5 to 18 months, with a median of 10 months. Eight patients are still disease free, with a median observation time of 13 months, but all had received additional therapy after two courses of this regimen. Gastrointestinal toxicity was frequent but tolerable. Myelosuppression was severe but of brief duration, ie, nadir of neutrophils was observed at day 15 with 95% of the patients recovering a normal count before day 28, and nadir of platelet count was at day 17 with only two severe and reversible episodes of bleeding. The overall incidence of sepsis was 8% (seven of 92 courses), with no death related to infection. No acute renal failure was observed after two courses, and only three of 47 children experienced a clear reduction of renal function. After two courses, only two children showed a hearing loss in the 1,000 to 2,000 Hz range, although hearing loss above the 2,000 Hz level was frequently encountered. It is concluded that high-dose VP-16 and CDDP is an effective regimen in advanced neuroblastoma with acceptable toxicity. Phase III studies are needed in previously untreated patients. J Clin Oncol 5:941-950.

High-dose chemotherapy and peripheral hematopoietic stem cell transplantation in relapsed/refractory Hodgkin’s lymphoma

2018 ◽  
Vol 104 (6) ◽  
pp. 471-475 ◽  
Author(s):  
Mouhammed Kelta ◽  
Jamal Zekri ◽  
Ehab Abdelghany ◽  
Jalil Ur Rehman ◽  
Zahid Amin Khan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
High Dose

Purpose: High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin’s lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. Methods: All patients ≥15 years old with relapsed/refractory Hodgkin’s lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. Results: Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. Conclusions: HDCT and ASCT for relapsed/refractory Hodgkin’s lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Long-Term Follow-Up of a Randomized Phase III Multicenter Study Comparing a Standard Versus an Intensified Conditioning Regimen for High-Dose Chemotherapy in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 945-945
Author(s):  
Roland Fenk ◽  
Peter Schneider ◽  
Martin Kropff ◽  
Ali-Nuri Huenerlituerkoglu ◽  
Ulrich Steidl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
High Dose ◽  
Significant Difference

Abstract High-dose chemotherapy (HDT) improves the outcome of patients with multiple myeloma (MM) in comparison to conventional chemotherapy. Dose-escalating strategies including tandem HDT are currently evaluated to further improve remission rates and survival of patients. Therefore we conducted a randomized multicenter trial to compare an intensified conditioning regimen with the current standard high-dose melphalan. The primary study endpoint was response rate, with overall survival (OS), event-free survival (EFS) and toxicity analysed as secondary endpoints. Between 1997 and 1999 a total of 56 patients with stage II and III disease, who were matched for age (median 56 years), number of previous therapies (median time from diagnosis to transplant 7 months) and different risk factors (beta2-microglobulin, LDH, CRP, cytogentic abnormalities, chemoresistant disease, IgA-subtype, renal impairment), were randomized. All patients received 2 courses of oral idarubicine/dexamethasone and 2 courses of intravenous cyclophosphamide/adriamycine in combination with G-CSF followed by peripheral stem cell collection. Thirty patients were treated with melphalan 200mg/m2 (HD-M) whereas 26 patients received idarubicine 42mg/m2, melphalan 200mg/m2 and cyclophosphamide 120mg/kg (HD-IMC) followed by autologous blood stem cell transplantation. Acute toxicity was higher with HD-IMC, including 5 (20%) treatment-related deaths due to infections versus none (0%) in the HD-M group. This lead to early termination of the study. Severity of mucositis (grade III-IV 19 vs. 8 pts., p=0.001), CRP (20 vs. 7 mg/dl, p<0.001), days of fever (11 vs. 3, p<0.001), days with iv-antibiotics (13 vs. 4, p<0.001), number of erythrocyte-transfusions (6 vs. 2, p<0.001), number of platelet-transfusions (16 vs. 4, p<0.001) and days to granulocyte engraftment (18 vs. 11, p=0.007) were significantly higher after HD-IMC. After a follow-up of 5 years analysis restricted to patients surviving the first 30 days after HDT showed a trend to higher response rates (CR+vgPR: 47% (95%CI 24–72%) vs. 35% (95%CI 18–56%), PR 37% (95%CI 17–63%) vs. 48% (95%CI 29–68%) and time-to-progression (median 31 vs. 15 months, p=0.1) in the HD-IMC treatment arm in comparison to HD-M, but there was no significant difference in EFS and OS (median 22 vs. 30, p= 0.31 and 66 vs. 66 months, p=0.8, respectively). Univariate analysis demonstrated that LDH levels > 200 U/L (p=0.04) and chemoresistant disease (p=0.05) were a bad prognostic factor for EFS. Beta2-Microglobulin levels > 5mg/dl (p=0.01), abnormal conventional cytogenetics (p=0.02) and LDH levels > 200 U/L (p=0.03) were predictive for an inferior OS. In conclusion intensified conditioning for HDT had an intolerable high treatment-related mortality and did not improve EFS and OS in patients with multiple myeloma.

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