Rituximab + IEV/MINE Second Line Approach in Relapsed/Refractory Non Hodgkin Lymphoma (NHL): Efficacy and Safety

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4954-4954
Author(s):  
Velia Bongarzoni ◽  
Barbara Anaclerico ◽  
Paola Anticoli Borza ◽  
Michele Cedrone ◽  
Anna Chierichini ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Second Line ◽  
High Dose Therapy ◽  
Who Grade ◽  
Dose Therapy ◽  
Cd 34 ◽  
Line Therapy

Abstract Background. Relapsed/refractory high grade NHL is a very aggressive pathology characterised by a poor prognosis. High dose therapy followed by peripheral blood stem cell (PBSC) rescue is to date the gold standard therapy. The results of high dose therapy are influenced by remission status after II line therapy as patients who undergo transplantation in complete response have better progression free survival with respect to those in partial response. While Rituximab+chemotherapy has become the approach of choice in 1st line-therapy, this type of schedule has not yet been largely applied in 2nd line therapy. In the aim of testing the efficacy of 2nd line-combined immuno-chemotherapy we designed a protocol including Rituximab + IEV/MINE. Methods. The planned treatment consists of 3 cycles of IEV or MINE (>65 y patients), plus Rituximab (375 mg/sqm) given on day +1 and on day +14 every cycle. G-CSF was administered from day 7 to ANC recovery and was continued until the CD 34+ collection after the third cycle. From April 2002 to July 2008 30 consecutive patients – 19 males and 11 females, median age 57 y (range 21–73 y) with refractory (12) and relapsed (18) Diffuse Large B Cell Lymphoma (DLBCL) entered the study. According to IPI score 20/30 patients were intermediatehigh risk; 21/30 had extranodal disease. Results. 27 patients completed treatment and are evaluable; 3 pts are not evaluable because of lethal infection after Ist cicle (2pts) and lost to follow up (1pt). 21/27 (78%) were responders: 12 (44%) achieved CR, 9 (33%) PR, while 6 progressive disease (PD) were withdrawn. Hematological toxicity including WHO grade III or IV neutropenia, anemia and thrombocytopenia was recorded in 19, 8 and 14 pts, respectively. Target CD 34 harvest was reached in 19/27 (70%) pts with CD 34+ median value 7,03 × 106/Kg. Among the responders 4 pts failed CD 34 harvest. 17/27 (63%) patients underwent transplantion, 11 autologous stem cell transplantation (ASCT) and 6 (>60 y) reduced intensity allogeneic-SCT. Of transplanted patients 4 (2 in CR post Mini Allo-SCT, 2 in relapse post ASCT) died 6, 2,10 and 10 months after transplantation, respectively. The remaining 13 (4 mini-alloSCT and 9 ASCT) are alive in CR which is lasting for 23 months median time (11–73). As of July 2008 15/27 (55%) patients are alive: 14 CR and 1 PR. Median follow up post R-IEV/MINE is 28 months (range 12–77), PFS was 38% and median OS is 32 months (range 7–90). Conclusions. Our experience, if limited to a small series of patients, shows that the addition of Rituximab to second line chemotherapy: increases response rate even in adverse IPI score cases, allows to obtain a good CD 34 harvest, represents an effective in vivo purging agent.

Use of Gemcitabine, Cisplatin and Methylprednisolone (GEM-P) with or without Rituximab in Relapsed and Refractory Patients with Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 939-939
Author(s):  
Bhawna Sirohi ◽  
David Cunningham ◽  
Andy Norman ◽  
Michele Trumper ◽  
Sheela Rao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progressive Disease ◽  
B Cell Lymphoma ◽  
Response Duration ◽  
Cardiac Insufficiency ◽  
High Dose ◽  
High Dose Therapy ◽  
Salvage Regimen ◽  
Dose Therapy

Abstract There is currently no standard salvage chemotherapy regimen in patients with relapsed/ refractory DLBCL. We have previously shown that GEM-P is an effective salvage regimen in patients with relapsed/refractory lymphoma; 10 patients in this study had DLBCL (Br J Cancer2005;92:1352–7). The aim of this study was to evaluate the combination of GEM-P in a larger subset of DLBCL patients. This has not been reported before. Between 1/01 and 3/05, 39 (10 patients had transformed lymphoma) heavily pre-treated relapsed and refractory DLBCL patients received GEM-P; 24 (61%) of these patients also received Rituximab (R). The median age was 49 y (range, 18–68); 28 males; 64% patients had Stage III/IV disease; 69% had IPI ≥2. The median time from diagnosis to start of GEM-P ± R was 17 mo (range, 2mo-7 yrs). All patients had previously received an anthracycline-based regimen. The disease status at start of GEM-P ± R was: 24 patients were in 1st relapse, 7 had primary refractory disease, 5 were in 2nd relapse and 3 in 3rd relapse. Median number of cycles of GEM-P ± R received were 2 (range, 1–4). The overall response rate (RR) was 59% (95% CI 42.1–74.4). 11 (28%) patients attained complete response, 12 partial response and 15 patients did not respond; 1 patient died of progressive disease. The median response duration to GEM-P ± R in 23 responding patients was 332 days (range, 36–1530) compared to 170 days (range, 26–2264) in 32 responding patients to 1st-line chemotherapy. Of the 24 patients who received R (not randomised; given when available via NHS funding network) with GEM-P, the overall RR was 67% (95% CI 45–84) compared to 47% (95% CI 21–73) in those who did not receive R (P=0.2). Eight patients were consolidated with high-dose therapy which was an autologous stem cell transplant (ASCT) in 7 (all are alive and well except one who relapsed 4 mo later and died of progressive disease) and a reduced intensity conditioning matched unrelated donor transplant in 1 patient who died of transplant-related complications. The remaining patients did not undergo an ASCT due to treatment failure (n=16), cardiac insufficiency (n=2) and subclavian vein thrombosis (n=1). ASCT was not planned in the other 12 patients because of indolent histology (n=2), inadequate stem cell collection (n=1), lost-to follow-up (n=1), previous high-dose therapy (n=3) and stage 1 disease (n=1), physicians decision (n=1), patients choice (n=1) multiply relapsed disease (n=2). Progression-free survival (PFS) and overall surveival (OS) are shown in the Table. 23 patients are alive at a median follow-up of 543 days (range, 76–1598). In conclusion, GEM-P is an effective salvage regimen with long response duration in patients with relapsed or refrcatory DLBCL. The additional benefit with Rituximab on outcome warrants further studies in new and relapsed patients with DLBCL in a prospective, randomised trial. Survival OS PFS GEM-P (n=15) 3-y 40%(95%CI 16–63) 1-y 27%(95%CI 8–49) GEM-P +R (n=24) 3-y 65%(95%CI 40–82) 1-y 51% (95%CI 28–69) GEM-P ±R (n=39) 3-y 53.4% (95% CI 35–69) Median 157d (95% CI 42–271) PFS by rituximab use PFS by rituximab use

High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem-Cell Transplantation for Adults ≥ 60 Years Old With Relapsed or Refractory B-Cell Lymphoma

2007 ◽  
Vol 25 (11) ◽  
pp. 1396-1402 ◽  
Author(s):  
Ajay K. Gopal ◽  
Joseph G. Rajendran ◽  
Ted A. Gooley ◽  
John M. Pagel ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Older Adults ◽  
Stem Cell ◽  
B Cell ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
Dose Therapy ◽  
Anti Cd20

Purpose The majority of patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) are older than 60 years, yet they are often denied potentially curative high-dose therapy and autologous stem-cell transplantations (ASCT) because of the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy. Patients and Methods Patients older than 60 years with relapsed B-cell NHL (B-NHL) received infusions of tositumomab anti-CD20 antibody labeled with 185 to 370 Mbq (5 to 10 mCi) [131I]-tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of [131I]tositumomab (median, 19.4 Gbq [525 mCi]; range, 12.1 to 42.7 Gbq [328 to 1,154 mCi]) to deliver 25 to 27 Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy. Results Twenty-four patients with a median age of 64 years (range, 60 to 76 years), who had received a median of four prior regimens (range, two to 14 regimens), were treated. Thirteen patients (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survival rates were 59% and 51%, respectively, with a median follow-up of 2.9 years (range, 1 to 6 years). All patients experienced expected myeloablation with engraftment of platelets (≥ 20 K/μL) and neutrophils (≥ 500/μL), occurring at a median of 9 and 15 days after ASCT, respectively. There were no treatment-related deaths, and only two patients experienced grade 4 nonhematologic toxicity. Conclusion Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.

Preliminary Results of a Prospective Randomized Study Comparing First Line Conventional Therapy Versus High Dose Therapy with Autologous CD34+ Purified Progenitor Cell Support in B CLL Patients with B and C Binet Stages: The GOELAMS LLC98 Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 152-152 ◽  
Author(s):  
Annie Brion ◽  
Beatrice Mahe ◽  
Brigitte Kolb ◽  
Bernard Audhuy ◽  
Philippe Colombat ◽  
...  
Keyword(s):  
Stem Cell ◽  
Skin Cancer ◽  
Disease Progression ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Stem Cell Support ◽  
Dose Therapy ◽  
Cell Support

Abstract The role of high dose chemotherapy with autologous stem cell support in first line therapy in patients with B-CLL remains to be defined. The aim of the prospective randomized GOELAMS LLC 98 (Groupe Ouest Est d’etude des Leucemies et Autres Maladies du Sang) trial was to compare two therapeutic strategies in previously untreated B-CLL patients younger than 60 years with B and C Binet stages. Conventional chemotherapy (Arm A) consisted of six monthly courses of CHOP, (i.e. vincristin IV 1 mg/m2 on day 1, doxorubicin IV 25 mg/m2 on day 1, cyclophosphamide (Cy) 300 mg/m2 and prednisone 40 mg/m2 both given orally from day 1 to day 5, followed by 6 CHOP courses every other 3 month in case of response. Fludarabine (25 mg/m2 /d IV for 5 consecutive days) was used in case of progression after 3 CHOP or non response after 6 CHOP. Conventional therapy was compared to high dose therapy with autologous CD34+ purified stem cell support (Arm B), using as consolidation of Complete Remission (CR) (NCI criteria) or Very Good Partial Response (VGPR, defined by >50 % tumoral response and < 30 % bone marrow lymphocyte count) obtained after 3 monthly courses of CHOP. In case of absence of CR or VGPR, 3 to 6 monthly-courses of fludarabine were realized before mobilization with Cy 4 g/m2 + G-CSF administration. Conditioning regimen included TBI 12 Gy and Cy 60 mg /kg /d for 2 days. Study end points included Event Free Survival (EFS), toxicity, feasibility. Between March 1999 and December 2004, 86 patients were randomized of which 79 were evaluable. A number of 38 patients were randomized to CHOP regimen and 41 to high dose therapy. The groups were well-balanced; 29% females, mean age 53 years (35 to 61), 67 % B and 25 % C Binet stages, 2 patients with A stage were included, 1 stage was not mentioned. In Arm B, 13 out of 41 patients were not transplanted because of disease progression (n=7), sepsis shock and death during the first CHOP course (n=1), patient’s refusal (n=1), graft contamination (n=1), mobilization failure (n=2) and violation criteria (n=1). CD34+ cells purification was performed in 69% of the grafts. Post transplant grade 3–4 non-hematological toxicity was mainly infectious (2 CMV and 1 aspergillus infections). Second cancers occurred in 3 patients in Arm A; skin cancer (n=1), breast cancer (n=1), Acute Myeloid Leukemia (AML) + skin cancer (n=1). One pretransplant case of skin cancer was reported in Arm B. Six patients died in Arm A from disease progression (n=5), AML (n=1) and 3 in Arm B from toxic death during the first course of CHOP (n=1), disease progression (n=2). As an intent-to-treat analysis and with a median follow-up time of 30 months (range 1–74), median EFS was 23.6 months in Arm A and 63.1 months in Arm B (p<0,001). In conclusion, front-line high dose therapy with autologous CD34+ purified stem cell support in B and C Binet stages B-CLL patients is feasible and has promising efficacy. Transplant-related toxicity appears to be acceptable. Longer follow-up as well as on-going VH mutational analysis will be necessary to precise the impact of autologous transplantation on overall survival in high-risk B-CLL.

Outcomes of Second-Line Chemotherapy and Autologous Stem Cell Transplantation for Primary Refractory Diffuse Large B Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4445-4445
Author(s):  
David Telio ◽  
Clement Ma ◽  
Richard Tsang ◽  
Armand Keating ◽  
Michael Crump ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Primary Treatment ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Primary Therapy ◽  
Second Line ◽  
High Dose Therapy ◽  
Large B Cell Lymphoma

Abstract Introduction: Patients (pts) with primary refractory Diffuse Large B Cell Lymphoma (REF DLBCL - defined as progession within 3 months of completion of primary therapy) sensitive to salvage chemotherapy are treated with high dose therapy and autologous stem cell transplantation (ASCT). The randomized Parma trial demonstrated survival benefit for patients with chemosensitive relapse undergoing ASCT but did not include primary refractory cases, thus current practice is based largely on retrospective series Methods: We conducted a retrospective review of 112 consecutive cases of REF DLBCL identified from our database between 1999–2007. All pts had evidence of stable or progressive disease (SD or PD) following primary treatment. Responses were assessed retrospectively using International Workshop Criteria (JCO 1999). Logistic regression was used to predict overall response rate (ORR) to salvage therapy; Cox Proportional-Hazards regression was used to analyze overall survival (OS) and progression-free survival (PFS). Salvage chemotherapy consisted of 2–3 cycles of platinum-based therapy; responding pts proceeded to PBSC mobilization and subsequent ASCT. High dose therapy consisted of VP16 60 mg/kg day –4 and melphalan 180 mg/m2 day –3 with PBSC infusion day 0. Pts with bulk disease (³ 5 cm) at progression received involved field radiation post-ASCT. Results: Median age was 46 (range 19–67); 77% had ECOG of 0–1 and 46% had limited stage disease at primary treatment failure. Where available (n=77), LDH was elevated in 74%. 21% had > 1 extranodal site. Primary treatment consisted of: CHOP 66%, R-CHOP 33% or ABVD 1%; radiotherapy was given in 15 pts. Response to primary therapy was: CR 9%, PR 31%, SD 20% and PD 41%. Second-line chemotherapy consisted of: DHAP 49, ESHAP 31, GDP (gemcitabine, dexamethasone, cisplatin) 24, or another platinum based-regimen 8. 5 pts received rituximab with the salvage regimen. ORR to first salvage chemotherapy was 24%. 2/35 pts receiving a second line and 0/6 pts receiving a third line of non-cross-resistant salvage therapy achieved response. 28 pts (25%) underwent ASCT. 6 pts received post-ASCT radiation as consolidation. With a median follow-up of 5.9 months (range 0.9–93.8), the median PFS and OS from primary treatment failure were 3 and 10 months respectively. OS may have been overestimated due to a high rate of loss to follow up after progression and subsequent censoring. In pts who underwent ASCT (median follow-up 18 months, range 0.3–89 months), median PFS was15 months after ASCT while median OS was not reached. ORR to salvage chemotherapy was predicted by normal LDH (OR=3.1; 95% CI=1.0–9.1; p=0.04). Proceeding to ASCT was predicted by normal LDH (OR=4.3; 95% CI=1.5–12.5; p=0.007), ECOG 0–1 (OR=5.2; 95% CI=1.1–23.6; p=0.03), and CR/PR with primary treatment (OR=3.2; 95% CI=1.5–12.3; p=0.01). Inferior PFS was found in pts with elevated LDH (HR=2.5; 95% CI=1.3–4.6; p=0.004), ECOG ≥ 2 (HR=1.8; 95% CI=1.1–2.9; p=0.01), and in pts having SD/PD with primary treatment (HR=1.7; 95% CI=1.1–2.6; p=0.02). OS was reduced in pts with elevated LDH (HR=5.3; 95% CI=1.8–15.0; p=0.002) and ECOG ≥ 2 (HR=2.7; 95% CI=1.4–5.2; p=0.004). Age, stage, number of extranodal sites and prior rituximab treatment were not significant predictors of any outcome. Conclusions: In summary, outcomes in patients with REF DLBCL are poor with an ORR of 25% to salvage chemotherapy and a median PFS of 15 months post-ASCT. Elevated LDH and poor functional status predict for inferior overall survival. Novel treatment approaches should be pursued in REF DLBCL.

High Dose Therapy / ASCT with Rituximab for In-Vivo Purging and Post-ASCT Consolidation in Relapsed Follicular Lymphoma Achieves Prolonged Clinical and Molecular Remissions.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 914-914 ◽  
Author(s):  
Anthony C. Woods ◽  
Rena Buckstein ◽  
Joy Mangel ◽  
Kevin Imrie ◽  
David Spaner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Patient Specific ◽  
High Dose ◽  
Molecular Remission ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Grade 3

Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is associated with prolonged remissions in relapsed follicular lymphoma (FL). Molecular remission in the graft and post ASCT predicts durable remissions and is a desirable endpoint. Rituximab (R) as an in vivo purge prior to HDT/ASCT and as consolidation after ASCT may help achieve this. To study this question, patients with relapsed FL were enrolled in a prospective, non-comparative phase II study between January 1998 and April 2000. Methods: 23 consecutive patients age <65 yrs with <3 relapses underwent HDT/ASCT with CBV (Cyclophosphamide, BCNU and VP-16) following salvage with CHOP or DHAP. Patients achieving ≥75% reduction in bulk and <15% marrow involvement underwent stem cell mobilization with chemotherapy plus G-CSF 10 μg/kg daily x 5. R 375 mg/m2 was given as a single-dose purge prior to collection, and repeated as 4 weekly courses at 2 and 6 months post-ASCT. Samples for PCR detection of minimal residual disease (MRD) were taken from stem cell grafts, as well as blood and marrow for all patients with detectable disease at baseline. Response assessments were clinical, laboratory and radiologic, and analysis was intention-to-treat. Results: Median cohort age at assessment was 50 yrs (32–57). Median number of prior regimens was 3 (1–7) and total treatment cycles was 9 (3–28). Median response duration to the preceding regimen was 10 months (1–86). Transplants were a median 2.4 years after diagnosis. At median follow-up of 4.5 yrs (1.3–6.3), there have been 10 relapses at a median of 2.8 yrs. 3 patients have died, 2 with relapse and one of presumptive sudden cardiac death. Significant toxicities were seen: 11 episodes of pneumonia (1 fungal), 4 episodes of herpes zoster (1 grade 3), 4 early episodes of grade 3/4 interstitial pneumonitis, and 1 episode each of grade 4 TTP and grade 3 optic neuritis. One patient developed AML at 4.7 years post-ASCT. Immune recovery has been delayed; at 600 days post ASCT, 16/18 (89%) of evaluable patients had not recovered IgG levels to normal. At baseline, 12/23 patients had detectable markers by PCR analysis (sensitivity 0.01%) for t(14;18) or patient-specific VDJ rearrangements in marrow or blood. Of these, all achieved at least a brief molecular remission in blood and marrow, 11/12 doing so pre-R consolidation. 5/12 patients have since relapsed at a median 3 yrs (2–4.5) post ASCT. Molecular relapse preceded clinical in 3/5 cases. 6/12 have had prolonged (median 4.8 yrs, range 3–5) molecular and clinical remissions. Median event-free survival for all patients is 63 months, with median overall survival not reached. Conclusions: HDT/ASCT with R for in vivo purging and post-ASCT consolidation for relapsed FL is feasible and associated with prolonged clinical and molecular remission. Delay in recovery of humoral immunity may play a role in the high incidence of infectious complications. A single infusion of Rituximab for in-vivo purging did not eradicate PCR detectable disease in the graft, although sustained molecular remissions of at least 24 months were achieved in 75% of evaluable patients post transplant, possibly due to post ASCT Rituximab consolidation. Whether this translates into survival benefit will require longer follow-up and further comparative studies.

Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2540-2544 ◽  
Author(s):  
Catherine Sebban ◽  
Nicolas Mounier ◽  
Nicole Brousse ◽  
Coralie Belanger ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Follicular Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Dose Therapy

AbstractThe purpose of this study is to compare our standard chemotherapy regimen (CHVP [cyclophosphamide, doxorubicin, teniposide, and prednisone]) plus interferon with 4 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by high-dose therapy with autologous stem cell transplantation (ASCT) in treatment-naive patients with advanced follicular lymphoma. Four hundred one patients were included from July 1994 to March 2001: 209 received 12 cycles of CHVP plus interferon α for 18 months (CHVP-I arm) and 192 received 4 cycles of CHOP followed by high-dose therapy (HDT) with total body irradiation and ASCT (CHOP-HDT arm). Overall response rates were similar in both groups (79% and 78% after induction chemotherapy, respectively). One hundred thirty-one of the 150 patients eligible for HDT underwent transplantation (87%). Intent-to-treat analysis after a median follow-up of 7.5 years showed that there was no difference between the 2 arms for overall survival (P = .53) or event-free survival (P = .11). Patients with a complete response at the end of the induction therapy had a statistically longer event-free survival and overall survival (P = .02 and < .001, respectively). After long-term follow-up, our study showed that there was no statistically significant benefit in favor of first-line high-dose therapy in patients with follicular lymphoma. High-dose therapy should be reserved for relapsing patients.

scholarly journals Prognostic Factors for Patients with Diffuse Large B Cell Lymphoma and Transformed Indolent Lymphoma Undergoing Autologous Stem Cell Transplantation in Denmark 2000-2012

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1983-1983
Author(s):  
Bente Arboe ◽  
Kristina Fruerlund Nielsen ◽  
Charlotte Madsen ◽  
Rasmus Heje Thomsen ◽  
Soeren Ramme Nielsen ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Refractory Disease ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Large B Cell

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is the largest subgroup of malignant lymphoma. Today more than 80% of the patients will achieve partial or complete remission. However more than 20 % will either relapse or present with refractory disease. The standard approach for patients without major comorbidity is salvage treatment followed by high dose therapy with autologous stem cell transplant (HDT). This potentially curative treatment is toxic with many side effects and procedure related mortality, and therefore identification of patients eligible for HDT is a difficult challenge. Objectives: Patients with relapse of de novo DLBCL and transformed indolent lymphoma (TIL) were included. The aim was to identify clinical prognostic markers that can identify patients who will not benefit from HDT. Methods: From the national lymphoma registry patients with relapse of B-cell lymphoma in Denmark in the period 2000-2012, who underwent HDT, were extracted. Medical records were reviewed for clinical, pathological, and treatment information, and outcome. Patients were followed until death or emigration or until February 1, 2015. The Kaplan-Meier method was used to estimate overall survival (OS) and progression free survival (PFS). Cox regression models were used to assess prognostic factors. Results: A total of 370 patients were included, 174 with de novo DLBCL, and 196 with TIL, 143 of the 196 had histologically confirmed transformation. Median age was 58 (22-73), and 59% of the patients were male. With a median follow-up of 82 months from HDT, the 5-year OS was 52% and the 5-year PFS was 44% (median PFS 3.2 years). For the DLBCL patients the 5-year OS was 43% and the 5-year PFS was 38%. For TIL patients the OS was 62% and the PFS 49% (figure 1). During the first 100 days, 29 patients (8%) were admitted to the intensive care unit (14 DLBCL), and only four of these patients were alive at six months. The non-relapse mortality (NRM) at day 100 was 6 % for both groups, after five years 25% for DLBCL and 15% for TIL. No significant difference in 5-year PFS was seen between sexes or age, but patients younger than 58 had better 5-year OS compared to patients aged 58 or above (p=0.047). There was no difference in relapse treatment (DHAP vs ICE). Smoking (ever vs. never) caused a significantly worse OS (p=0.034). All IPI-factors, except Ann Arbor stage, was of prognostic importance (PFS). Primary refractory disease was of poor prognostic importance (p=0.001), and in patients, for whom the time from last salvage treatment to reinfusion of stem cells was more than 2 months, had a worse outcome (p=0.006). Patients, with less than 20 days of hospital admission in the period from the date of relapse to start of HDT, had a significantly higher survival (OS and PFS) (p>0.001). In a multivariate analysis (PFS), LDH above upper normal reference, HR 1.4 (95% CI: 1.0;2.1), involvement of more than one extranodal site, HR 1.6 (1.1;2.3) primary refractory disease, HR 1.6 (1.1;2.3) and more than two earlier relapses, HR 1.9 (1.1;3.5) were all factors associated with adverse outcome. For OS, the multivariate analysis showed, that patients with TIL had a better outcome, HR 0.7 (0.5;0.9), compared to DLBCL. Age above 58, HR 1.5 (1.1;2.1), involvement of more than one extranodal site, HR 1.9 (1.4;2.8), and primary refractory disease, HR 1.6 (1.1;2.3) were factors associated with adverse outcome. Discussion: In this population based study we find a 5-year OS of 52% after HDT and a 5-year PFS of 44%. Patients with TIL have a significantly higher 5-year PS (49%) than patients with de novo DLBCL (38%) whereas NRM is identical for the two groups at day 100 (6%). However, NRM increases subsequently more for DLBCL than for TIL over time to 25% and 15 % respectively after five years. Furthermore we show that hospitalization days less than 20 and postponement of stem cell infusion beyond 2 month after harvest may be useful parameters that can identify patients that have better or worse outcome after HDT. This nationwide study cohort with the long follow-up period is applicable to a general population of patients, and this may explain the somewhat lower outcome compared to other published HDT cohorts. Figure 1. Progression Free Survival (PFS) curves for Diffuse Large B-Cell Lymphomas (DLBCL) and Transformed Indolent Lymphomas (TIL) after high dose therapy with autologous stem cell transplant Figure 1. Progression Free Survival (PFS) curves for Diffuse Large B-Cell Lymphomas (DLBCL) and Transformed Indolent Lymphomas (TIL) after high dose therapy with autologous stem cell transplant Disclosures Brown: Bayer: Consultancy; Roche: Consultancy, Speakers Bureau.

The Impact of Histologic Grade on the Outcome of High-Dose Therapy and Autologous Stem Cell Transplantation for Follicular Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 679-679
Author(s):  
Rosalyn N. Pham ◽  
Ted A. Gooley ◽  
Grant E. Keeney ◽  
Oliver W. Press ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
B Cell Lymphoma ◽  
Histologic Grade ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
The Impact

Abstract Follicular lymphomas (FL) represent approximately one-fourth of all non-Hodgkins lymphomas (NHL) and are the most common indolent lymphomas. Studies suggest that patients (pts) with relapsed FL treated with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) have prolonged progression-free survival (PFS) and overall survival (OS) as compared to those treated with standard chemotherapy alone, yet the impact of histologic grade on these outcomes has not been established. In order to address this issue, we evaluated all FL pts that underwent HDT and ASCT at our center from Dec 1985 to June 2005 (n=219). Pts with transformation to diffuse large B-cell lymphoma were excluded. Histologic grades 1, 2, and 3 were present in 106 (48%), 75 (34%), and 38 (17%) pts, respectively. Other baseline characteristics at the time of transplant for this cohort included: Female = 39%, median age = 48 (range 24 – 66), stage III/IV = 93%, elevated LDH = 27%, median number of prior regimens = 3 (range 1 to 11), prior radiation therapy (RT) = 16%, bulk ≥5cm = 19%, chemosensitive = 68%, complete remission = 18%. 53% of pts are alive and 36% are alive without relapse at last contact leading to 5- and 10-year estimates of 60% and 42% for OS and 39% and 28% for PFS, respectively. The median follow-up for surviving patients was 7.8 years. The 5- and 10-year OS estimates for the histologic grades were grade 1: 57% and 42%, 2: 60% and 36%, and 3: 65% and 55% (Figure). Five- and 10-year PFS estimates were grade 1: 35% and 27%, grade 2: 44% and 25%, and grade 3: 45% and 40% (Figure). In order to adjust for any potential imbalances of critical prognostic factors between the three grades, we performed a multivariable analysis adjusting for criteria that were found to be associated with OS and/or PFS (age, # of prior regimens, prior RT, chemosensitivity, and LDH) and obtained the hazard ratios (HR) and p-values noted (Table). These data suggest that 1) prolonged OS and PFS can be attained via HDT and ASCT in FL pts, 2) histologic grade does not statistically significantly impact outcomes, and 3) other factors noted above should be utilized to predict outcome and counsel patients. Grade HR for Death (95% CI) p HR for Death or Progression (95% CI) p 1 1 (– –) – 1 (– –) – 2 1.00 (0.66–1.54) 0.98 0.92 (0.63–1.34) 0.69 3 0.66 (0.35–1.24) 0.20 0.79 (0.48–1.33) 0.38 Figure Figure

The Outcome of Different Types of Second-Line Therapy in Multiple Myeloma Patients Relapsing After Uniform Front-Line Treatment with High-Dose Melphalan and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2892-2892
Author(s):  
Claudia Crippa ◽  
Samantha Ferrari ◽  
Monica Drera ◽  
Marinella Calarco ◽  
Antonio Regazzoli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
High Dose Melphalan

Abstract Abstract 2892 Poster Board II-868 Background and aim. While multiple myeloma (MM) still remains largely incurable, therapeutic options for patients with MM are expanding. However the best way to use the different effective regimens, either in combination or in sequence, during the course of MM in the single patient is still unknown. Data from controlled studies rarely report the treatments received before and after the enrollment of patients in the clinical trial, which may significantly impact on response and survival. As an example, the best treatment for patients relapsing after first-line high-dose melphalan (HD-Mel) and autologous stem cell transplantation (ASCT) is not standardized. To this end we have retrospectively analyzed an uniform cohort of such patients treated at our Institution, comparing their outcome according to the type of second-line and further consolidation treatment received. Patients and methods. In 156 patients affected by MM and treated between 1997 and 2008 with HD-Mel and ASCT as first line therapy, relapse has occurred in 92 (59%). Females were 39 (42%), males 53 (58%), median age was 60 (range 34-75). As induction therapy before ASCT, 89 (97%) had received VAD regimen, and only 3 (3%) thalidomide/bortezomib-based regimen. Sixty-one patients (66%) had received a single ASCT and 31 a double ASCT (34%). A second-line therapy was given to 87/92 patients. They were subdivided in 3 subgroups according to the type of second-line treatment received: 1) thalidomide-based regimens (THAL) were given to 55 pts (63%) followed by a consolidation ASCT in 13 (24%) 2) bortezomib-based regimens (BORT) were used in 13 (15%) and subsequent ASCT in 3 of them (23%) 3) chemotherapy and/or steroids (CHEMO) were used in 19 (22%) followed by ASCT in 15 (79%). Median follow-up from diagnosis was 57 (13-145) in THAL, 39 (17-140) in BORT and 59 months (25-113) in CHEMO respectively. The baseline characteristics, including age, of the three subgroups were similar as well as the CR/VGPR and ORR rates obtained after first-line treatment (THAL 47% and 87%; BORT 69% and 100%; CHEMO 53% and 100%, respectively). The subgroups also did not differ in median duration of first response, which ranged from 13 to 15 months and median time to second treatment, which was 26 months in all subgroups. The proportion of patients receiving a double ASCT were significantly higher in BORT (69%) compared to THAL (34%) (P=0.03) and CHEMO (5%) (p=0.002), and in THAL (34%) compared to CHEMO (5%) (p=0.015). Results. After second line therapy the ORR (CR+VGPR+ PR) of the three subgroups was: THAL 60%, BORT 77% and CHEMO 58%. (p=NS). The second CR/VGPR rate was non significantly higher after BORT (46%) than after THAL (25%) or CHEMO (21%) (p=0.17). Moreover, when considering patients not undergoing second-line consolidation ASCT, the ORR was significantly better in THAL and BORT subgroups compared to CHEMO (50%, 70% and 0%, respectively p=0.03). After a median follow-up from second-line treatment of 28 months (range 1-99), the 2-y PFS was 38% after THAL (median 18 months), 34% after BORT (median 16 months) and 17% after CHEMO (median 12 months) (p=NS). The 2-y OS was 78% (median 49 months), 70% (median not reached), and 70% (median 33 month) after THAL, BORT and CHEMO, respectively (p=NS). However when considering patients not undergoing second-line consolidation ASCT, the 2-y OS was significantly better after THAL and BORT than after CHEMO (p=0.024). Conclusion. In spite of having frequently received a first-line double ASCT, BORT patients seemed to achieve responses of better quality. However, in patients relapsing after first-line HD-Mel and ASCT, the choice of THAL, BORT or CHEMO-based regimens as second-line therapy did not seem to impact on overall response rates and survival, provided that patients treated with CHEMO could be consolidated with a second ASCT. Hence newer drugs may be reserved for those patients not fit for ASCT, preserving them for effective third-line treatment in the other patients. Disclosures: No relevant conflicts of interest to declare.

High-Dose Therapy and Autologous Blood Stem-Cell Transplantation Compared With Conventional Treatment in Myeloma Patients Aged 55 to 65 Years: Long-Term Results of a Randomized Control Trial From the Group Myelome-Autogreffe

2005 ◽  
Vol 23 (36) ◽  
pp. 9227-9233 ◽  
Author(s):  
Jean-Paul Fermand ◽  
Sandrine Katsahian ◽  
Marine Divine ◽  
Veronique Leblond ◽  
Francois Dreyfus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Blood ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Blood Stem Cell Transplantation

Purpose To study the impact of high-dose therapy (HDT) with autologous stem-cell support in patients with symptomatic multiple myeloma (MM) between the ages of 55 and 65 years. Patients and Methods One hundred ninety patients between 55 and 65 years old who had newly diagnosed stage II or III MM were randomly assigned to receive either conventional chemotherapy (CCT; ie, monthly courses of a regimen of vincristine, melphalan, cyclophosphamide, and prednisone) or HDT and autologous blood stem-cell transplantation (using either melphalan alone 200 mg/m2 intravenous [IV] or melphalan 140 mg/m2 IV plus busulfan 16 mg/kg orally as pretransplantation cytoreduction). Results Within a median follow-up of 120 months, median event-free survival (EFS) times were 25 and 19 months in the HDT and CCT groups, respectively. Median overall survival (OS) time was 47.8 months in the HDT group compared with 47.6 months in the CCT group. A trend to better EFS (P = .07) was observed in favor of HDT, whereas OS curves were not statistically different (P = .91). The period of time without symptoms, treatment, and treatment toxicity (TwiSTT) was significantly longer for the HDT patients than for the CCT patients (P = .03). Conclusion With a median follow-up time of approximately 10 years, this randomized trial confirmed a benefit of HDT in terms of EFS and TwiSTT but did not provide evidence for superiority of HDT over CCT in OS of patients aged 55 to 65 years with symptomatic newly diagnosed MM.

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