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

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.

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.

Final Analysis of a Randomized, Phase III, Trial Using Etoposide and G-CSF with or without Rituximab (R) for Peripheral Stem Cell Mobilization (PSC) in B-Cell Non-Hodgkin Lymphoma (B-NHL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 300-300 ◽  
Author(s):  
Brad Pohlman ◽  
Lisa Rybicki ◽  
Elizabeth Kuczkowski ◽  
Stacey Brown ◽  
Matt Kalaycio ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Critical Issue ◽  
Phase Iii ◽  
High Dose ◽  
Significant Difference

Abstract R is commonly combined with chemotherapy and has been shown to improve the outcome of patients (pts) with both indolent and aggressive B-NHL. R is increasingly administered prior to PSC mobilization to in vivo purge the PSC product. Some non-randomized, primarily retrospective, studies have suggested that R administration prior to PSC mobilization has no impact on CD34 cell collection but might have other short-term detrimental effects. We conducted a prospective, randomized trial of chemotherapy-based PSC mobilization with or without R. All pts had B-NHL and were eligible for autologous stem cell transplantation (ASCT). Pts were excluded if they had received R within 8 weeks prior to registration. Pts were randomized to receive one of two mobilization regimens (MR): etoposide (VP16) 2 gm/m2 and G-CSF 10 mcg/kg/day alone (VPG) or 3 doses of R 375 mg/m2 at 2 weeks, 1 week, and 1–2 days prior to VP16 2 gm/m2 and G-CSF 10 mcg/kg/day (VPG-R). PSC collection was begun when WBC &gt;1000 and continued in an attempt to collect at least 7 x 106 CD34/kg. The primary endpoint was CD34/kg yield. 76 pts were enrolled. 11 VPG and 10 VPG-R pts were not evaluable: 7 VPG and 4 VPG-R pts never received any MR; 4 VPG and 6 VPG-R dropped out or were removed from the study prior to initiation of the assigned MR. 27 VPG and 28 VPG-R pts received the assigned MR and were evaluable for CD34 collection. The two groups were well balanced for pt and disease characteristics. Five pts [4/27 (14.8%) VPG and 1/28 (3.6%) VPG-R] failed to collect ≥2.0 x 106 CD34/kg (p=.15). There was no statistically significant difference in the number of pheresis days or total CD34 yield between the two MR groups. Compared to the VPG pts, the VPG-R pts tended to collect more CD34/kg during the first two days of pheresis. 50 B-NHL pts (15 follicular, 34 diffuse large B-cell, and 1 other) received the assigned MR (23 VPG and 27 VPG-R), collected ≥2 x 106 CD34/kg, and subsequently received high dose busulfan, VP16, cyclophosphamide and ASCT. There was no significant difference in the number of CD34/kg infused, days until ANC &gt;500 or platelets &gt;20K, length of hospitalization, decrease in 6 week post-ASCT pulmonary diffusion capacity, or 6 week or 6 month (mo) post-ASCT hypogammaglobulinemia. One VPG-R pt developed transient neutropenia 3 mo post-ASCT. During the first 6 mo post-ASCT, fatal pneumonitis occurred in 1 VPG and 2 VPG-R pts, and fatal infections occurred in 1 VPG and 1 VPG-R pts. With a median follow-up among surviving pts of 39 (1–59) mo, there is no significant difference in freedom from progression (FFP), progression-free survival (PFS), or overall survival (OS). We conclude that the administration of R immediately prior to PSC mobilization has no adverse effect on CD34 yield. The two week delay from the last salvage chemotherapy regimen to the administration of VP16 in the VPG-R group has no detrimental impact on disease outcome and may actually enhance PSC collection during the first two days of pheresis. Furthermore, our data suggests that R immediately prior to PSC mobilization has no clinically significant effect on short- or long-term complications. Whether R administration prior to PSC mobilization improves FFP, PFS, or OS awaits longer follow-up and larger studies powered to address this critical issue.

scholarly journals Efficacy and safety of high-dose chemotherapy with in vivo purged auto-SCT in relapsed follicular lymphoma: long-term follow-up

2009 ◽  
Vol 45 (6) ◽  
pp. 1119-1120 ◽  
Author(s):  
M Magni ◽  
M Di Nicola ◽  
C Carlo-Stella ◽  
L Devizzi ◽  
A Guidetti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Efficacy And Safety ◽  
Long Term Follow Up

Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.

1995 ◽  
Vol 13 (5) ◽  
pp. 1089-1095 ◽  
Author(s):  
W P Vaughan ◽  
E Kris ◽  
J Vose ◽  
P J Bierman ◽  
P Gwilt ◽  
...  
Keyword(s):  
Phase I ◽  
Continuous Infusion ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Rank Test ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Stem Cell Rescue

PURPOSE A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.

In Vivo Purging Followed by AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) in PATIENTS with MULTIPLE MYELOMA (MM): Preliminary RESULTS of a Pilot STUDY

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4458-4458
Author(s):  
Imma Attolico ◽  
Domenico Vertone ◽  
Nunzio Filardi ◽  
Michele Pizzuti ◽  
Monica Poggiaspalla ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Pilot Study ◽  
Conditioning Regimen ◽  
Optimal Schedule ◽  
High Dose ◽  
Phase Ii Trials ◽  
Pbsc Mobilization

Abstract In the past decade, thalidomide, bortezomib, and lenalidomide have emerged as highly active agents in the treatment of MM. However, the optimal schedule and association of these drugs is still under investigation. Thalidomide has shown to be highly thrombogenic in induction therapy, especially in patients with high tumor burden, while Bortezomib (BOR) is not; moreover BOR does not affect peripheral blood stem cell (PBSC) collection and it has also been used in combination with Melphalan (MEL) before ASCT. Both in vitro laboratory data and preliminary phase II trials suggest synergistic effects when BOR is combined with Cyclophosphamide (CY); this drug is effective in treatment of MM and is not stem cell toxic. We started a pilot study in high risk MM patients, fit for ASCT, combining BOR, CY and dexamethasone (DEX) as induction and mobilizing therapy (CY-BOR), followed by supplemented BOR-ASCT, to determine: 1-feasibility and Response Rate (RR): percentage of complete remission (CR) and near CR (nCR) at day + 90 after ASCT; 2- clearance of Minimal Residual Disease (MRD) both in PBSC harvest and in bone marrow at day +90 after SCT; the percentage of plasma cells (PC) in PBSC harvested has been assessed by flow cytometry (FC), by using CD38, CD45, CD56, CD138, CD19, kappa and lambda staining. Patients receive three 3-weeks treatment cycles with BOR 1.3 milligrams/squared-meter/dose on days 1,4,8,11, in combination with DEX 40 milligrams/day i.v. on days 1,4,8,11 and CY i.v. 300 milligrams/squared-meter/dose on days 1,8,15. After the third course, patients achieving at least PR, undergo PBSC mobilization with BOR 1.3 milligrams/squared-meter/dose on days 1,4,8,11 in combination with DEX 40 milligrams/day i.v. on days 1,4,8,11 and CY i.v. 3000 milligrams/squared-meter/dose on day 8; Granulocyte-Colony Stimulating Factor (5 micrograms/kilogram) is given starting on day 9. Patients who successfully mobilize an adequate PBSC amount are planned to receive conditioning regimen, combining high-dose MEL(on day -1) with BOR (1.3 milligrams/squared-meter/dose on days -8 and -4). At present 10 patients (6 female and 4 male; median age: 71) have been enrolled and 8 are evaluable for response before PBSC harvest; 4 patients have been mobilized: in all of them we were able to collect a sufficient PBSC amount (median 11.1; range 3–11.2 CD34+ cells/kilograms) and to perform ASCT. Conditioning was well tolerated and was followed by quick engraftment: the median time to neutrophils&gt;500/mcl was 9 days and 12 days for unsupported platelets count&gt;20,000/mcl, without major extrahematological toxicity. With a minimum follow-up of 90 days after ASCT, 3 evaluable patients are alive, two in VGPR and one in CR; with a median follow up of 108 days (range 95–201) all 10 patients are alive and 100% of the evaluable patients achieved at least PR after only 2–3 courses of CY-BOR (table 1). The hematological toxicity was negligible and we did not observe neither thromboembolic events nor grade 3–4 neurotoxicity. Only one patient experienced a transient increase of liver enzymes during the first two courses of therapy. The study of MRD by flow cytometry in PBSC harvest of two evaluable patients shows complete clearance of plasmacells; in the others the MRD study is still ongoing and complete data will be further presented. This preliminary experience shows that this schedule is well tolerated and very effective also in elderly patients, allowing to collect a clonal plasmacells free harvest. Whether this will translate in an “in vivo” MRD clearance after ASCT, it should be confirmed by a longer follow up and by a PCR monitoring with patients specific probes (which is still ongoing). Pts UPN Age Sex Stage ISS Previous lines of treatment Response before PBSC mobilization Harvest: CD34+ cell amount SCT Status at last Follow-up 1 59 F III A III 1 nCR 3,99×106/kg Yes A&W (CR) 2 68 M III B III 2 nCR 11×106/kg Yes A&W (nCR) 3 73 F III A III 0 VGPR 11,2×106/kg Yes A&W (VGPR) 4 72 F III A II 1 VGPR 3×106/kg Yes A&W (VGPR) 5 69 M II A I 0 PR NE NE A&W 6 77 F III A II 1 PR NE NE A&W 7 52 M III A III 0 PR NE NE A&W 8 74 F III B II 2 VGPR. NE NE A&W 9 64 F II B II 3 N.E. NE NE A&W 10 73 M III A II 0 N.E. NE NE A&W Table 1: Baseline characteristics of patients and outcome Legenda: ISS: International Staging System; NE: not evaluable; A&W: alive and well; VGPR: very good partial remission

Radioimmunotherapy (RIT) with 90yttrium Zevalin Followed by BEAM Conditioning Regimen (Z-BEAM) and Autologous Stem Cell Transplantation (ASCT) for the Treatment of High Risk Relapsed/Resistant Non Hodgkin's Lymphoma (NHL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3107-3107
Author(s):  
Barbara Botto ◽  
Chiara Ciochetto ◽  
Marilena Bellò ◽  
Roberto Passera ◽  
Giulia Benevolo ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Standard Dose ◽  
Bone Marrow Involvement ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Matched Pair ◽  
High Dose ◽  
Bulky Disease ◽  
Response Status

Abstract Abstract 3107 High dose chemotherapy (HDC) and ASCT is actually considered an effective treatment for relapsed NHL. Standard dose Zevalin (0.4 mCi/kg) combined with conventional BEAM (Z-BEAM) is a promising conditioning regimen for the treatment of high risk relapsed/resistant NHL. We evaluated the feasibility and the efficacy of Z-BEAM in a group of relapsed/refractory patients treated in a single institution. Between October 2006 and December 2010 twenty nine pts were treated with Zevalin (day –14) followed by standard dose BEAM (day –7 to –1) and ASCT. Patients were included into the study and considered at high risk of failure if showed: progression or early relapse (<1 year) from previous therapy or multiple relapses. Rituximab followed by standard dose DHAP or ICE were used as debulking and mobilizing schedule. Clinical characteristics were as follows: 14 refractory and 15 early or multiple relapse; 8 grade I-II follicular, 16 PML/DLBCL, 3 MCL, 2 indolent non follicular; 6 stage II and 23 stage III-IV; 10 patients had bulky disease and 15 bone marrow involvement; 9 LDH level above normal. 13 patients received only one previous line of treatment and 16 were treated with 2 or more lines before Z-BEAM, all containing Rituximab. Only 5/29 patinets received a reducted dose of 0.3 mCi/kg Zevalin because of low platelets counts. Response status before RIT was: 14 CR (49%), 9 PR (33%), 3 SD (9%) and 3 PD (9%). At the end of treatment response status is actually available in 26/29 pts: CR 18(69%), PR 5(19%) and PD 3 (12%). Overall response rate was converted from 81% before Z-BEAM and ASCT to 88% at the end of the entire program. Median CD34+ cells infused was 7.26 106/kilograms (range 4.43–8.9). All pts engrafted with median time to platelet and neuthrophils count higher than 20×109/l and 0.5×109/L of 11 and 10 days respectively. Febrile neutropenia occurred in 12/29 pts. One pulmonary Aspergillosis and 8 bacteriemia were documented. One patient experienced an intestinal perforation during aplasia and one cardiac failure was documented in a woman previously treated with cumulative antraciclines doses and mediastinal radiotherapy. With a median follow up of 15 months progression free survival (PFS) is 79% and overall survival is 83%. 4/14 pts before Z-BEAM showed a subsequent progression and 2/15 relapsed: five pts died of lymphoma. No toxic deaths were recorded. In this group of pts with high risk relapsed/resistant NHL Z-BEAM+ASCT is able to achieve a good response with engraftment and toxicity not different from standard BEAM. This approach needs to be tested in a larger multicenter study. A matched pair analysis to compare this group with a similar group treated with standard BEAM without Zevalin is actually planned in our institution Disclosures: No relevant conflicts of interest to declare.

Paclitaxel-based high-dose chemotherapy (HDCT) for relapsed or refractory germ cell tumors (GCTs): Clinical outcome and quality of life (QOL) in long-term survivors.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 325-325
Author(s):  
Sumanta Kumar Pal ◽  
Virginia Sun ◽  
Courtney Carmichael ◽  
Betty R. Ferrell ◽  
Paul Henry Frankel ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Life Questionnaire ◽  
Long Term Survivors

325 Background: HDCT is a viable and potentially curative approach for patients with relapsed or refractory GCTs. However, no comparative data exist to define the optimal chemotherapeutic strategy. Herein, long-term follow-up data and QOL assessments are provided for an expanded cohort of patients treated with high-dose paclitaxel, etoposide, carboplatin, and ifosfamide (TECTIC). Methods: Details of the TECTIC regimen and clinical follow-up data for an initial 33 patients have been previously reported (Margolin Biol Blood Marrow Trans 2005). Surviving patients were surveyed using a modified EORTC Quality of Life Questionnaire-30 (QLQ-C30) and the Functional Assessment of Cancer Therapy-Taxane (FACT-T) questionnaire; results were compared to relevant historical cohorts using a 2-sample t-test. Cardiovascular morbidity (CM) was ascertained through queries regarding use of antihypertensive (AH) or cholesterol-lowering (CL) agents, and presence/absence of diabetes mellitus (DM). Results: Forty-six patients received protocol-based therapy. Of these, 17 patients were progression-free at a median of 112.7 mos (49.5-170.2), and 6 patients remain alive following progression with a median overall survival (OS) of 64.4 mos (43.6-147.1). Median progression-free survival (PFS) and OS were 11.8 mos (95%CI 5.8-NR) and 21.7 months (95%CI 12.7-NR), respectively. Of the 23 patients still alive, 18 patients were accessible and consented to telephonic interview. As compared to historical cohorts (Rossen J Clin Oncol 2009), survivors had a higher global health scale score (87.04 v 75.62; P=0.02) but a lower physical functioning score (68.89 v 92.66; P=0.0001) by the QLQ-C30 scale. No difference in FACT-T scores were observed as compared to historical cohorts (Cella Cancer 2003). Four patients (22%) had DM. Three patients (17%) and 4 patients (22%) reported use of AH and CL agents, respectively. Conclusions: HDCT with the TECTIC regimen produces durable remissions in patients with relapsed or refractory GCTs, with acceptable QOL and CM in long-term survivors.

Dose Intensity of Chemotherapy in Patients With Relapsed Hodgkin's Lymphoma

2010 ◽  
Vol 28 (34) ◽  
pp. 5074-5080 ◽  
Author(s):  
Andreas Josting ◽  
Horst Müller ◽  
Peter Borchmann ◽  
Joke W. Baars ◽  
Bernd Metzner ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Stage Iv ◽  
Dose Intensity ◽  
High Dose Chemotherapy ◽  
Observation Time ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Significant Difference ◽  
Multiple Relapse ◽  
The Impact

Purpose High-dose chemotherapy (HDCT) followed by autologous stem-cell transplantation (PBSCT) has become the standard treatment for patients with relapsed Hodgkin's lymphoma (HL). The intensity of treatment needed is unclear. This European intergroup study evaluated the impact of sequential high-dose chemotherapy (SHDCT) before myeloablative therapy. Patients and Methods Patients with histologically confirmed, relapsed HL were treated with two cycles of dexamethasone, cytarabine, and cisplatin, and those without disease progression were randomly assigned. In the standard arm (A), patients received myeloablative therapy with carmustine, BEAM (carmustine, etoposide, cytarabine, and melphalan) followed by PBSCT. Patients in the experimental arm (B) also received sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM. Freedom from treatment failure (FFTF) was the primary end point. Remission rates, overall survival (OS), and toxicity of treatment were secondary end points. Results From a total of 284 patients included, 241 responding patients were randomly assigned after two cycles of dexamethasone, cytarabine, and cisplatinum. Patients treated in arm B had longer treatment duration and experienced more toxicity and protocol violations (P < .05). Mortality was similar in both arms (20% and 18%). With a median observation time of 42 months, there was no significant difference in terms of FFTF (P = .56) and OS (P = .82) between arms. FFTF at 3 years was 62% (95% CI, 56% to 68%) and OS was 80% (95% CI, 75% to 85%). Patients with stage IV, early relapse, multiple relapse, anemia, or B symptoms had a higher risk of recurrence (P < .001). Conclusion Compared with conventional high-dose chemotherapy, additional SHDCT is associated with more adverse effects and does not improve the prognosis of patients with relapsed HL.

scholarly journals Comparison of Two Post-Transplant Predictive Indexes: Day 100 is a Better Time-Point for Response Evaluation after Autologous Stem Cell Transplantation in Multiple Myeloma: Ass Retrospective Study

2020 ◽  
Vol 7 (8) ◽  
Author(s):  
Ma’koseh M ◽  
◽  
Sa’deh S ◽  
Halahleh K ◽  
Abu-Jazar H ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Response Evaluation ◽  
Therapeutic Implications ◽  
Significant Difference

In Multiple Myeloma (MM), response to High-Dose Chemotherapy (HDC) and Autologous Stem Cell Transplant (ASCT) has important prognostic and therapeutic implications. Best timing for response evaluation after ASCT is not well studied. Our study evaluated the correlation between response on day 30 and day 100 after ASCT with Progression Free Survival (PFS) and Overall Survival (OS) in 119 MM patients. Median follow-up was 39.8 months. Complete Response (CR) was achieved in 53.8% and 55.5% of patients on D 30 and D 100, respectively. On D30, there was no significant difference in PFS or OS in CR vs. no CR group (35.4 vs. 22.1 months, p: 0.058) and (92.6 months vs. not reached p: 0.96) respectively nor in responders (R) vs. Non-Responders (NR) group (97.8 vs. 47.1 months p: 0.08) and (30.2 vs. 18.9 months, p: 0.09) respectively. While on D100, PFS was significantly better in CR vs. no CR group (33.8 vs. 18.1 months, p: 0.0047) as well as in R vs. NR (30.6 vs. 16.9 months p: 0.015). However, OS was not better in either (92.6 vs. 52.1 months p: 0.46) and (92.6 months vs. not reached p: 0, 88) respectively. In conclusion, after HDC and ASCT for MM, we recommend doing response evaluation on D100 rather than D30 as it better correlates with PFS. Further studies are required to confirm this finding in the era of consolidation and maintenance treatment.

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