Long-Term Disease-Free Survival in Patients with Relapsed/Refractory Follicular Lymphoma After Autologous Stem Cell Trasplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2031-2031
Author(s):  
Pablo A Garcia ◽  
Guillermina Remaggi ◽  
Diego A de Goycoechea ◽  
Sebastian Yantorno ◽  
Maria Marta Rivas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Salvage Therapy ◽  
Conditioning Regimen ◽  
Disease Stage ◽  
High Dose ◽  
Free Survival ◽  
Grade 3

Abstract Abstract 2031 Background: The role of High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT) as salvage therapy in relapsed Follicular Lymphoma (FL) has been questioned since the introduction of Rituximab in the treatment of FL. Our objectives were to evaluate the long-term event-free survival (EFS) and overall survival (OS) rates of patients with relapsed or refractory FL who received HDT and ASCT as salvage therapy. Our secondary objective was to compare EFS of patients who received ASCT before and after 2002 (the year Rituximab become fully available for use in our country). Patients and Methods: We conducted a retrospective analysis of 123 consecutive patients with relapsed or refractory FL who had received HDT and ASCT as salvage therapy in five Argentinean transplant centers from 1992 to 2012. Results: One hundred twenty tree patients (median age: 48 years, range: 23–72) were transplanted, 71 (58%) male, 37/106 (35%) had FL Grade 1, 47/106 (44%) FL Grade 2 and 22/106 (21%) FL Grade 3; 75/102 (73%) of patients have a stage III-IV disease at the moment of diagnosis and 27/102 (26%) have a disease stage I-II. Before transplantation 78/121 (64%) patients were in Complete Response (CR), 42/121 (35%) were in Partial Response (PR) and one patient had a Progressive Disease. Fifty four patients (44%) were transplanted before 2002 (before Rituximab era in our country). The conditioning regimens used were CBV 94 (76%), BEAM/BEAC 27 (22%), others regimens two patients; only one patient received TBI containing conditioning regimen and was excluded for conditioning regimen PFS curve calculation. The median time from FL diagnosis to ASCT was 29 (range 1–300) months. The transplant related mortality (until day 90 after ASCT) was 5%. With a median follow-up of 52 (range 0–247)months, the median EFS was reached at 44 months and a plateau on the EFS curve was evident starting at 6 years after ASCT. The 10 years-projected EFS was 36% (Figure 1). The median OS was not reached during follow-up. Median EFS for patients who were transplanted before 2002 (before Rituximab era) and for those who were transplanted after 2002 was 41 months and 47 months respectively [HR 1.01; IC (0.61–1.65); p=0.97]. EFS rates difference was not statically significant between patients who previously transplantation have achieved a CR or a PR, median EFS 47 and 68 months respectively [HR 0,94; IC (0,56–1,58); p= 0,82]. There was no difference in EFS rates between patients who received CBV as conditioning regimen and patients who received BEAM/BEAC, median EFS 57.6 months and 16.3 months respectively [HR 0.67; IC (0,34–1.35); p=0.2]. The median EFS rate for patients with FL Grade 1, FL Grade 2 and FL grade 3 were 58, 44 and 16 months respectively, P for trend = 0.78. Seven cases (5,7%) of secondary malignancies were detected, six cases (6/94; 6,4%) in patients who received CBV as conditioning regimen (urotelial carcinoma, pancreas carcinoma, lynfoprolipherative disorders, non-melanoma skin malignancies and prostate carcinoma) and one case (1/27; 3,7%) in patients who received BEAM (urotelial carcinoma), p=0,85; there were no reports of secondary myelodysplastic syndromes/acute myeloid leukemia. Conclusion: In this study, 50% of the patients analyzed were free from progression after 44 months of ASCT and approximately a 30% of patients achieve long term remission. According to this, patients with relapsed or refractory FL can achieve long-term EFS with HDT followed by ASCT. Disclosures: No relevant conflicts of interest to declare.

Long Term Follow-Up of 4-Hydroperoxycyclophosphamide Purged Autologous Bone Marrow Transplantation in Non-Hodgkin’s Lymphoma Patients with High Risk of Bone Marrow Involvement.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5234-5234
Author(s):  
Elise A. Chong ◽  
Charalambos Andreadis ◽  
Stephen J. Schuster ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Tumor Cells ◽  
Platelet Transfusion ◽  
High Dose ◽  
Free Survival

Abstract Introduction: High-dose chemotherapy and autologous stem cell transplant (ASCT) can result in long term survival for patients with advanced non-Hodgkin’s lymphoma (NHL) but relapse remains a common cause of treatment failure. Bone marrow (BM) involvement is common in NHL and there is controversy over whether or not reinfusion of BM stem cells contaminated by clonogenic tumor cells is a major cause of relapse following ASCT. Bone marrow purging can reduce the number of tumor cells in vitro, but the impact on relapse and disease free survival (DFS) remains unknown. Methods: Between 1990 and 1993, 20 pts with poor prognosis NHL (B-symptoms, high LDH, bulky adenopathy, stage III or IV, or relapsed disease) at high risk for BM involvement underwent 4-hydroperoxycyclophosphamide (4-hc) purged BM transplantation. Thirteen pts had low grade B-cell NHL, 6 had an intermediate grade B-cell NHL with a small B-cell component, and 1 had T-lymphoblastic lymphoma. Seven of 20 pts had received ≥3 prior chemotherapeutic regimens. Three pts underwent transplantation in first complete remission and 17 pts were in chemotherapy-responsive relapse. At diagnosis, 11 of 20 pts had documented BM involvement, and at ASCT, 6 of 20 pts had BM involvement (all < 5% involvement at BM harvest). Eighteen pts (90%) received 4-hc purged autologous BM, and 2 pts (10%) received 4-hc purged autologous BM and peripheral stem cell support. High dose regimens included Cytoxan/TBI (85%), BCV(10%), and Melphalan/TBI (5%). The median age was 45 yrs (range: 20–57 yrs). The median nucleated cell count of 4-hc marrow that was reinfused was 2.4 × 108 /kg (range: 0.87–5.5). The median time to granulocyte recovery was 26 days (range: 14–59). Two pts died at days 31 and 35 without achieving platelet transfusion independence. In the remaining 18 pts, the last platelet transfusion was given at a median of 29 days post-marrow infusion (range 18–149), and the median in-patient hospital days was 27 (range: 16–82 days). Results: There were 2 deaths (fungal infection and CNS relapse) during ASCT. One pt died in CR after developing secondary AML 5.34 yrs after ASCT. Post-ASCT, 18 of 20 pts achieved CR (including 1 pt who had no evidence of disease at autopsy), 1 pt had a PR, and 1 pt died during BMT and was not evaluable for response. Median follow-up for the group was 8.2 yrs (range: 0.1–12.4 yrs). At last follow-up, 9 pts remain in CR (1 died of AML in CR), 5 pts had relapsed and remain alive, and 5 pts died of progressive disease. Median follow-up for survivors was 11.1 yrs (range: 5.2–12.4 yrs). 65% of pts remain alive at last follow-up. The median EFS was 9.4 yrs (range: 0.1–12.4 yrs). Those who achieved a CR post-ASCT had a median DFS of 10.6 yrs (range: 1.1–12.4 yrs). At 8.2 yrs, 4/6 pts with involved BM at the time of harvest had relapsed or died compared to 7/14 pts with negative BM which is not significantly different. Conclusion: ASCT using 4-hc BM purging is feasible and can result in long term relapse free survival, even for pts with subtypes of NHL at high risk for BM involvement. Whether 4-hc BM purging is equivalent or superior to immunologic approaches to stem cell processing remains to be determined.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

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 Tandem Autologous Followed By Nonmyeloablative Allogeneic Transplantation in Relapsed High Risk Follicular Lymphoma Leads to Excellent Long Term Progression-Free Survival after 8 Years of Follow-up

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4677-4677
Author(s):  
Magalie Tardif ◽  
Imran Ahmad ◽  
Nadia M. Bambace ◽  
Lea Bernard ◽  
Lambert Busque ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Median Time ◽  
Progression Free Survival ◽  
Disease Status ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival

Abstract Many new therapeutic agents have been approved for follicular lymphoma (FL) but none appear to be curative. Despite novel agents, some patients (pts) experience early relapse, become chemorefractory or suffer transformation into more aggressive lymphomas. Options for these pts are limited. High dose chemotherapy with autologous stem transplant (ASCT) prolongs progression free survival (PFS) and overall survival (OS) in FL pts in first relapse and registry data shows favorable outcome with ASCT in cases of histologic transformation. However, ASCT is usually not curative. Myeloablative allogeneic transplant (MT) has produced long term PFS but is hampered by significant non relapse mortality (NRM) while nonmyeloablative transplant (NMT) has a higher relapse rate compared to MT especially in high risk pts. Finally, many transplant studies have excluded these high risk pts such as those with chemorefractory or transformed disease. We hypothesized that a tandem transplant consisting of an ASCT followed by a NMT would confer the same benefit as a MT without the associated high NRM by separating the high dose chemotherapy from graft versus host disease (GVHD) while preserving the graft versus lymphoma effect. The goal of our study was to improve long term PFS in high risk FL pts. We therefore initiated a prospective protocol in April 2003, for pts with high risk relapsed FL as defined by chemorefractory disease, early 1st relapse, >1st relapse or transformation into aggressive histology. At least one therapy was attempted to document chemosensitivity prior to ASCT. However, regardless of disease status prior to transplant, pts underwent ASCT followed 3 months later by an outpatient NMT from an HLA-identical sibling. NMT comprised 5 days of fludarabine 30 mg/m2/day and cyclophosphamide 300mg/m2/day followed by an infusion of >2x106CD34+ cells/kg. GVHD prophylaxis, chosen to take advantage of the low incidence of acute (a) GVHD and the putative protective effect of chronic (c) GVHD, consisted of tacrolimus starting on day (D) - 8 to achieve levels of 8-12 nmol/L then tapered off by D+100 or D+180 depending on disease risk and of mycophenolate mofetil 1g bid from D+2 to D+50. We previously reported on 27 pts with a follow-up (f/u) of 3 years (yrs). We now report a larger cohort of 40 pts with a median f/u of 8 yrs. Up until July 2015, 40 pts were enrolled with a median age of 50 yrs (34-65). Pts had previously been treated with a median of 3 lines of therapy (2-6). Median time from diagnosis to ASCT was 33 months. Disease status at ASCT was: 14 CR, 16 PR and 10 refractory. Conditioning for ASCT included BEAM/BEAC (n=39), and Cy-TBI (n=1). In addition, 4 pts received radiotherapy after ASCT to sites of previously bulky disease. Median time between ASCT and NMT was 138 days (75-238). Pre NMT disease status was: 25 CR, 12 PR and 3 refractory. Engraftment was prompt in all pts after ASCT and median neutrophil and platelet recovery were respectively 13 days (0-19) and 0 day (0-18) post NMT. Seven pts (18%) developed aGVHD: 2 grade II and 5 grade III. Overall, 29 pts (73%) developed cGVHD: 1 mild, 13 moderate and 15 severe according to NIH revised criteria. Median time to discontinuation of immunosuppression was 22 months. To date, 2 pts have progressed at 11 and 59 months post NMT (one died from relapse and one is now in CR after chemotherapy and DLI) and 5 pts died from either GVHD related complications (n=4) or unknown cause (n=1). All pts alive at last f/u were in CR. With a median f/u of 8 yrs in surviving pts (1-12), OS is 95% at 3 and 5 yrs and 82% at 8 yrs. PFS is 92% at 3yrs, 89% at 5 yrs and 80% at 8 yrs. NRM and relapse rate at 8 yrs are 18% and 6% respectively. Based on our current results in 40 pts, we conclude that ASCT followed by sibling NMT for high risk relapsed FL is associated with excellent disease response and PFS. Furthermore, this tandem strategy appears to be safe and well tolerated. The incidence of cGVHD remains high but could in part explain the impressive PFS in this high risk cohort. This approach should now be further explored in a multi institution setting, include matched unrelated donors and consider the addition of rituximab post-transplant to reduce the incidence and severity of cGVHD with the hope that relapse will not be increased. Figure 1 Figure 1. Disclosures Busque: Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

A Single Institution Long-Term Experience Using Autologous Stem Cell Transplantation for the Management of Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5233-5233
Author(s):  
Barry S. Skikne ◽  
Narotham Thudi ◽  
Delva Deauna-Limayo ◽  
Siddhartha Ganguly ◽  
David Bodensteiner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
Primary Induction ◽  
Induction Failure

Abstract Patients with stage III – IV Hodgkin’s lymphoma (HL), and those with bulky stage I/II disease have a disease relapse rate of 30–40% after primary treatment. High dose chemotherapy with stem cell transplantation is a treatment option after relapse or in those with primary induction failure. In the present study, we retrospectively examined long term outcomes in 45 relapsed/primary induction failure HL patients undergoing autologous peripheral stem cell (25 patients), bone marrow (17 patients) or combination (3 patients) transplantation between 1985 and December 2003. The median age was 32 yrs(16–64), 38 had Nodular Sclerosing HL, 17 patients had stage I/II, 13 stage III and 15 stage IV disease, and 33 had B symptoms at diagnosis. Twenty patients were previously treated with 1–2 prior regimens, while 25 had ≥3 treatment regimens. Sixteen patients had sensitive disease to salvage therapy given prior to transplantation, 27 had resistance to salvage therapy while 2 did not undergo salvage therapy prior to transplantation. Five patients had primary resistant disease, 33 had evidence of relapsed disease and 7 patients were in CR at the time of transplantation. CBV was used in 30 patients, BEAM in 9 patients and 5 patients received CY/TBI based regimens. Six patients (13%) had early mortality (< 100 days) directly attributable to the procedure. Four of these deaths were cardiac related and two were due to infection. The overall response was 93% with CR achieved in 28 (62%) and incomplete response in 14 (31%). The median overall survival (OS) was 5.5 yrs, the median disease free survival (DFS) was 1 yr with DFS at 5 yrs of 26%. For patients achieving a CR after transplantation, 67% remain alive at a median of 7 yrs from transplant, however, the median progression free survival in these patients was 3.7yrs. For 15 patients not achieving CR after transplantation, 3(20%) have survived, the median time to death in this group was 20 months. Seventeen patients are alive, 2 are lost to follow-up and 21 patients have died. Fourteen patients died from disease progression (31%), 2 (4%) died from MDS/AML occurring after 32 and 66 mnths, 2 died of late occurring infections, 2 related to respiratory failure and a further patient from late cardiac failure. OS and DFS did not differ between peripheral stem cell vs bone marrow transplantation, those with B symptoms at diagnosis, sex differences, age <20yrs vs >20yrs, high dose therapy regimens but a difference in OS (p=0.04) and DFS (p=0.03) was seen in patients transplanted in CR vs active disease at transplantation. Patients whose disease displayed sensitivity to salvage therapy immediately prior to transplant did show a trend towards improved OS and DFS, but this was not statistrically significant. High dose chemotherapy and autologous stem cell transplantation can be expected to lead to long term DFS in approximately 25–35% of patients. Cardiac mortality (11%) appears to be a higher than expected complication in this patient group.

Busulfan, Melphalan, and Bortezomib Compared to Single Agent High-Dose Melphalan As a Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma: Long Term Follow up of a Novel Conditioning Regimen

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2023-2023 ◽  
Author(s):  
Patrick Hagen ◽  
Anita D'Souza ◽  
Parameswaran Hari ◽  
Omar Davila ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Phase Ii ◽  
Research Funding ◽  
Single Agent ◽  
Conditioning Regimen ◽  
High Dose

Introduction: Multiple myeloma (MM) remains incurable when treated with novel myeloma therapies in combination with high dose chemotherapy and autologous stem cell transplantation (ASCT). In contrast to the accelerated development of effective new drugs for induction, maintenance, and relapse, single-agent melphalan remains the standard for conditioning before ASCT. Is this phase II trial, we prospectively evaluated a conditioning regimen consisting of high-dose intravenous busulfan and melphalan followed by bortezomib (BUMELVEL), an agent shown to be potentially synergistic in combination with alkylating agents. We report our 7 year long term follow up with direct comparison to a contemporaneous CIBMTR cohort with the primary aim of both long term progression-free (PFS) and overall survival (OS). Methods: This phase I/II study was conducted between July 2009 and May 2012 at Loyola University Medical Center. MM patients with any disease response following induction were enrolled at time of stem cell transplantation. 43 patients received BUMELVEL conditioning followed by ASCT on the phase II portion of this study. Busfulan was administered intravenously (i.v.) daily for 4 days with the first 2 days (days −6 and −5) at fixed dose of 130 mg/m2 over 3 hours and the subsequent 2 doses (days −4 and −3) adjusted to achieve a target AUC total of 20,000 μM·min determined by pharmacokinetic (PK) analysis. Melphalan at 140 mg/m2 and bortezomib at 1.6 mg/m2 were administered i.v. on days −2 and −1, respectively. Maintenance therapy was not planned. Patients received prophylaxis for oral mucositis with palifermin. Data from this phase II clinical trial were compared against a matched control cohort of contemporaneous North American MM patients from the CIBMTR database (n = 162) receiving conditioning with single agent iv melphalan at a dose of 200mg/m2. The primary objectives of this study were median PFS and toxicities. Results: Baseline patient characteristics are described in Table 1. More patients in the BUMELVEL arm received greater than one line of therapy prior to transplant (53 v 33%). There were more standard risk patients per Mayo Stratification (Kumar et al, Mayo Clin Proc 2009) in the MEL200 group (78%) v the BUMELVEL group (40%). There was no difference in response rates at day 100 (p=0.48) but a trend toward improved response at 1 year in the BUMELVEL arm with 77% achieving a VGPR or better versus 60% in the MEL200 group (p-0.09). No patients in the BUMELVEL group received planned maintenance therapy post-transplant whereas 112 (69.6%) in the MEL200 control arm received planned post-transplant maintenance. Non-relapse mortality was 2% (range 0-9%) in the BUMELVEL group and 10 (6%, range 3-11) in the MEL200 but this was not statistically significant in both univariate and multivariate modeling (p=0.25). There were no episodes of sinusoidal obstructive syndrome in the BUMELVEL group and 37% of patients experienced grade 3 mucositis with no grade 4 mucositis. After a median of more than seven years of follow up, the five year PFS was 47% (95% CI; 32-62) in the BUMELVEL group versus 30% (95% CI; 23-37) in the MEL200 group (p=0.05) (Figure 1). Notably the 7-year PFS in the BUMELVEL group was 32% (range 18-48). In multivariate analysis for PFS, BUMELVEL conditioning (HR 0.65; 95% CI 0.44-0.97)(p=0.036), time from diagnosis to transplant of greater than versus less than 12 months (HR 1.64; 95% CI 1.18 - 2.27), and disease status at transplant CR versus other (p=0.006) were all predictive of PFS (table 2). OS was not different between the two groups with a 7 year survival of 64% (95% CI; 48-79) in the BUMELVEL group versus 55% (95% CI; 46-64%) in the MEL200 group (Figure 1) which was confirmed on multivariate analysis (p=0.33). Discussion: Similar to recent reports in the literature comparing busulfan and melphalan to melphalan alone (Bashir et al, Lancet Hem 2019), we show that although depth of response was similar between the BUMELVEL group and the historical MEL200 comparator, the BUMELVEL group experienced an improved PFS. Importantly, we report no cases of SOS and a low non-relapse mortality of only 2% (v 6% in the historical control) reinforcing that the preparatory regimen in myeloma can be intensified safely with improved duration of unmaintained PFS. These long term results confirm a sustained benefit of novel combination conditioning in MM and the need for novel transplant preparative regimens. Disclosures D'Souza: EDO-Mundapharma, Merck, Prothena, Sanofi, TeneoBio: Research Funding; Prothena: Consultancy; Pfizer, Imbrium, Akcea: Membership on an entity's Board of Directors or advisory committees. Hari:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Research Funding; Spectrum: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding; Cell Vault: Equity Ownership; AbbVie: Consultancy, Honoraria. Stiff:Unum: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Cellectar: Research Funding; Amgen: Research Funding; Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding.

Remission Duration ≤ 12 Months for Early Relapsed and Refractory Follicular Lymphoma Is Predictive of Early Failures Post-High Dose Therapy and Autologous Stem Cell Rescue.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3136-3136
Author(s):  
Matthew A Lunning ◽  
Jocelyn C Maragulia ◽  
Craig H. Moskowitz ◽  
Matthew J. Matasar ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
Stem Cell Rescue ◽  
Remission Duration

Abstract Abstract 3136 Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the Western hemisphere and is likely incurable with chemotherapy alone. Despite a median overall survival exceeding 12 years in the modern era, a fraction of patients experience an aggressive clinical course characterized by short remission duration(s) and/or chemorefractory disease. While high-dose therapy and autologous stem cell rescue (HDT-ASCR) is an accepted treatment modality for prolonging progression-free survival (PFS) it is unlikely to provide cure. Allogeneic stem cell transplantation (alloSCT) is a definitive therapy that has been shown to produce long-term disease free remissions. Unfortunately, alloSCT is limited by the risk of transplant-related mortality (TRM) despite the advent of non-myeloablative (NMA) conditioning regimens. Given that many FL patients whom fail HDT-ASCR may not proceed to alloSCT, and the inherent difficulty in deciding the appropriate consolidative transplant modality, we conducted a retrospective exploratory analysis of clinical features of early and multiply relapsed FL patients undergoing first HDT-ASR or alloSCT at a single center in the modern, post-rituximab era. Methods: We retrospectively reviewed all patients with early relapsed and/or refractory FL that proceeded to HDT-ASCR or NMA alloSCT as first transplant at MSKCC between 2006 and 2010. Chemosensitive disease was defined as a partial response (PR) or complete response (CR) to the last treatment regimen prior to transplant by computed tomography scans per IWG Criteria (Cheson et al JCO 1999). Events were defined as progression of FL post-transplant or death from any cause. Event-free survival (EFS) and overall-survival (OS) were estimated using Kaplan-Meier method. Results: We identified 40 patients with relapsed or refractory FL who had undergone either first HDT-ASCR (N=20) or alloSCT (N=20). All patients had FL grade 1–3a without pathologic evidence of transformation at the time of re-induction prior to transplant consolidation. Patient characteristics are outlined in the table below: All HDT-ASCR patients received BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning. All alloSCT patients received a uniform non-myeloablative conditioning regimen (cyclophosphamide, fludarabine, total body irradiation 200 cGy). The median follow-up for survivors is 34 months. The estimated 3 year-EFS and OS was 60% and 62% with HDT-ASCR and 79% and 85% with alloSCT respectively (p=ns). FL patients with remission duration ≤ 12 months prior to re-induction therapy proceeding to consolidative HDT-ASCR had significantly shorter EFS compared to those patients with previous remission duration > 12 months (p<0.05, figure 1). Furthermore, when HDT-ASCR and alloSCT patients with a previous remission duration ≤ 12 months prior to re-induction therapy were compared the estimated 3-year EFS was 79% for alloSCT and 36% for HDT-ASCR (p<0.03, figure 2). With relatively short follow-up, there was no difference in OS for these two groups. In the HDT-ASCR cohort eight events were related to progression of FL with three of the eight patients subsequently undergoing alloSCT. In the alloSCT cohort four events occurred with one patient developing DLBCL and three TRM (2-related to graft-versus-host disease; 1-cytomegalovirus infection). Conclusion: The management of relapsed/refractory follicular lymphoma remains a clinically complex topic. In this exploratory analysis we demonstrated that remission duration of ≤ 12 months prior to re-induction chemotherapy is suggestive of inferior disease control with HDT-ASCR. Longer follow-up is necessary to determine the OS impact. Given the relatively unfavorable pre-transplant characteristics of the alloSCT cohort, FL appears to be exquisitely sensitive to an allogeneic effect. TRM continues to limit the benefit of alloSCT. Disclosures: Matasar: GSK: Research Funding; Genentech: Consultancy.

scholarly journals Long-Term Recurrence-Free Survival after an Unplanned Reduction in Radiotherapy for HPV-Positive Oropharyngeal SCC: Two Cases and a Review of the Literature

2017 ◽  
Vol 96 (7) ◽  
pp. E23-E27 ◽  
Author(s):  
Jason Liu ◽  
David Goldenberg ◽  
Salah Almokadem ◽  
Henry Crist ◽  
Heath B. Mackley
Keyword(s):  
High Dose ◽  
Review Of The Literature ◽  
Free Survival ◽  
Concurrent Radiotherapy ◽  
Grade 3 ◽  
To Receive ◽  
Negative Counterpart ◽  
Severe Mucositis

There is currently no clear distinction between the treatment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive OPSCC has been demonstrated to be more radiosensitive than its HPV-negative counterpart. Despite this, patients with HPV-positive OPSCC continue to receive a full dose of radiation (70 Gy) outside clinical trials. However, this high dose comes with considerable morbidities, including severe mucositis, dysphagia, and xerostomia. We describe the cases of 2 patients with HPV-positive OPSCC who received two cycles of high-dose cisplatin at 100 mg/m2 on 3 separate days, along with concurrent radiotherapy at 50 Gy in 25 fractions for one and 46 Gy in 23 fractions for the other. During treatment, both patients experienced significant acute-phase toxicities—including grade 3 mucositis, grade 3 nausea, and grade 2 dermatitis—and their treatment regimen was stopped before its planned completion. Nevertheless, after a follow-up of 75 and 78 months, respectively, neither patient exhibited any evidence of disease. Late toxicities included grade 1 xerostomia, grade 1 pharyngeal-phase dysphagia, and grade 1 dysgeusia with some foods. We conclude that de-escalating the dose of radiation for HPV-positive patients by 30% and identifying which patients can safely be treated with this level of dose reduction warrants further study.

scholarly journals Long Term Follow up and Impact of Comorbidity Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory AML - Lessons Learned from the Prospective Bridge Trial -

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4692-4692
Author(s):  
Jan Moritz Middeke ◽  
Regina Herbst ◽  
Stefani Barbara Parmentier ◽  
Gesine Bug ◽  
Mathias Hänel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Study Enrollment ◽  
Long Term Follow Up

Abstract In patients with relapsed or refractory (r/r) Acute Myeloid Leukemia (AML), allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered to be the only treatment providing long-term disease control for fit patients. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy prior to HSCT in patients with r/r AML. Here, we report the long-term follow up of this Phase II, multi-center, Intent-To-Transplant study and the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range 40 - 75) were enrolled. Patients were scheduled for at least one cycle of salvage therapy with CLARA (clofarabine 30 mg/m2 and cytarabine 1 g/m2, days 1-5). Chemo-responsive patients with a donor received HSCT after first CLARA. In the event of a prolonged donor search, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine 30 mg/m2, day -6 to -3, and melphalan 140 mg/m2 on day -2. The ECOG score, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and Cumulative Illness Rating scale (CIRS) were obtained at study enrolment as well as prior to HSCT. Sixty-seven percent of the patients received HSCT within the trial. After a median follow up of 40months (95% CI, 38-49 months), the estimated 4-year OS (Figure 1) for all enrolled patients was 38% (95% CI, 28-50%) and Disease-Free Survival for transplanted patients was48% (95% CI, 36-64%). The CIR at four years was 30% (95% CI, 17-43%) and the NRM 22% (95% CI, 10-33%).Those patients who received an allogeneic HSCT within the trial had a median HCT-CI at the time of study enrollment of 1 (range, 0 - 6) compared to a median of 2 (range, 0 - 6) for those who did not proceed to allogeneic HSCT (p = .17). Corresponding figures for the CIRS were a median of 2 (range, 0 - 9) compared to 4 (range, 0 - 8) (p = .09). The median ECOG score was 1 (range, 0 - 3) in both groups. Compared to the time point of study enrollment, both the HCT-CI as well as the CIRS increased to a median of 2 (observed range of score, 0 - 7) and a median of 4 (observed range of score, 0 - 12), respectively, at the time of start of the conditioning regimen. This was almost exclusively due to an increase in infectious complications (Figure 2). Inmultivariate analysis, both the baseline HCT-CI and the ECOG score had a statistically significant impact with a HR of 1.22 (p = .025) and 1.72 (p = .001), respectively, on OS. Using a clofarabine-based salvage therapy combined with early allogeneic HSCT we were able to achieve good long-term results for patients with r/r AML. In this cohort, both the HCT-CI and the ECOG score gave prognostic information on OS, showing feasibility of comorbidity evaluation at the time of diagnose of r/r AML. Figure 1 OS of all enrolled patients Figure 1. OS of all enrolled patients Figure 2 Changes of the HCT-CI at baseline to HSCT Figure 2. Changes of the HCT-CI at baseline to HSCT Disclosures Middeke: Sanofi: Honoraria. Rösler:Janssen: Consultancy, Other: Travel/Accommodation/Expenses. Thiede:AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document