Phase I/II Trial of High-Dose Melphalan (M) and Topotecan (T) Followed by Autologous Stem Cell Rescue in Patients ≤ 60 and > 60 Years of Age with Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 943-943
Author(s):  
Daniel Sullivan ◽  
Melissa Alsina ◽  
Claudio Anasetti ◽  
Teresa Field ◽  
Mohamed Kharfan-Dabaja ◽  
...  
Keyword(s):  
Stem Cell ◽  
Total Dose ◽  
Dose Level ◽  
Topoisomerase I ◽  
Plasma Cells ◽  
The Elderly ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Grade 3

Abstract MM is the most common indication for high-dose chemotherapy (HDC) and autologous stem cell rescue. Among 13,431 pts receiving HDC for MM, the 3-year probability of survival is 67% ± 1% with autotransplantation (IBMTR data). Pre-clinical data from our lab demonstrate a synergistic cytotoxic interaction from sequential M and topoisomerase I inhibitors in human MM cell lines. Thus, we conducted a trial where poor prognosis chemosensitive, relapsed, and primary refractory pts were primed for stem cell collection with cyclophosphamide (50 mg/kg/d X 2d) and GCSF. Pts were then treated with fixed doses of M (50 mg/m2/d X 3d; total dose = 150 mg/m2) followed immediately by dose-escalated T (6.7–56.7 mg/m2/d X 3d; total dose = 20–170 mg/m2) in separate cohorts of younger (≤ 60) and elderly (> 60) patients with MM. The standard dose of M was decreased to allow for dose-escalation of T. One hundred nineteen patients are evaluable for toxicity, response and survival (54 elderly and 65 younger). The maximum tolerated dose (MTD) in the elderly cohort is 30 mg/m2 total dose T (dose level 2); dose-limiting toxicity (DLT) at 40 mg/m2 was grade 3 musculoskeletal toxicity. The median age of the elderly pts was 65 yrs (range 61–77). The MTD in younger patients was a total T dose of 127.3 mg/m2 (dose level 7); DLT at 170 mg/m2 was grade 4 transaminitis. The median age of the younger pts was 53 yrs (range 33–60). The response rate (CR + PR) in elderly subjects (includes 38 pts enrolled at the MTD) was 65%, and 77% in those ≤ 60 (7 pts enrolled at the MTD thus far). Grade 3–4 mucositis was common at all dose levels of T and increased in incidence with T dose-escalation. Median days to ANC ≥ 500/ml X 3d for all patients was d+11, and for platelets ≥ 20K X 7d was d+16. No correlation between time of engraftment and dose level was observed. The 100 day non-relapse mortality was 1.7% (one patient died from sepsis and one from ARDS). At a median follow up of 25.3 and 35.3 months for the elderly and young cohorts, respectively, the 3-year overall survival is 70% for both groups. At a median follow up of 15.3 months for the elderly and 14 months for the young cohort, the 3-year event-free survival is 32% and 40%, respectively. The pharmacokinetics of high-dose M and T have been determined in all patients on this trial, and the AUC and CMAX of T appear to be linear with dose. Pts with stable disease after transplant were found to have an increased clearance of melphalan and a lower AUC of T lactone and T total drug. SNP analyses of 71 pts using the Nanogen DrugMet SNP genotyping assay showed that CYP3A5*3 carriers appear to have increased T metabolism that is associated with a poorer response to MT. The relative risk a CYP3A5*3 allele carrier would have a PR or SD was 1.77 with a 95% CI of 1.37–2.28. The remaining goals of this trial are to enroll 43 pts at the MTD for both the young and elderly cohorts, to determine topoisomerase I levels and distribution in CD138-selected plasma cells, and to define the levels and function of the ABCG2/BCRP pump in plasma cells (for which T is the best substrate). This trial was supported in part by NCI grant CA082533 and GlaxoSmithKline.

Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM) Patients over Age 70.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4952-4952
Author(s):  
Carla Borgono ◽  
Young Trieu ◽  
Wei Xu ◽  
Jacob Pendergrast ◽  
Donna Reece ◽  
...  
Keyword(s):  
Stem Cell ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
The Elderly ◽  
High Dose ◽  
Post Transplant ◽  
Co Morbidity ◽  
Cd34 Cells ◽  
Grade 3

Abstract Introduction: MM is a disease of the elderly with a median age of 65 years at diagnosis. Melphalan-based ASCT is standard therapy for younger (<60–65 years) MM patients (pts). However, limited data are available on the efficacy of ASCT in pts over age 70 with concerns of excess toxicity and transplant-related mortality (TRM). Methods: In this retrospective study, we examined the feasibility of ASCT in 33 MM pts ≥ age 70 (median age 71 yrs; range 70–74) who underwent this procedure at Princess Margaret Hospital from October 2000 to August 2006. As per institutional standard, all pts received 3–6 cycles of high-dose dexamethasone (DEX)-based induction therapy (VAD or DEX-alone) and underwent standard stem cell mobilization with cyclophosphamide 2.5g/m2 and GCSF 10mg/kg/day. Routine ciprofloxacin prophylaxis and GCSF use (from day 7) were used during the transplant process. Results: Nineteen pts(58%) were male. Baseline lab values (at time of transplant) were as follows: median hemoglobin 106g/L(range 83–144), WBC 6.7x109/L(range 1.9–11.9), platelets 191x109/L(range 103–319) and creatinine 69mmol/L(range 43–191mmol/L). Pre-transplant ECOG was 0–2 for all pts. Co-morbidities were reported for 29 pts(88%) and included prior solid tumours(18%) and cardiac disorders (arrhythmia, infarction) (15%). MM isotypes included: IgG 22(67%), IgA 6(18%), IgD 1 (3%), biphenotypic IgA/IgM 1(3%), nonsecretory 3(9%). A median of 9.1x106 CD34 cells/kg body weight (range 2.2–25.4x106cells/kg) were collected. Median time to engraftment of neutrophils and platelets was 12 days(range 9–13) and 11 days(range 8–15), respectively. Median duration of hospitalization was 15 days (range 12–40). Transfusion support (red cells and/or platelets) from time of stem cell collection to day 100 post-ASCT was required in 30/33 (91%) pts. Responses (all PR) were achieved in 24/27 pts (89%) with measurable disease. At a median follow-up of 18.3 months (mos) post-transplant, 16 pts (50%) relapsed and 14 (44%) died (follow-up data available in 32 pts). Median progression-free survival (PFS) was 23.3 mos; median overall survival (OS) was 41.2 mos from transplant. Three-year PFS and OS were 70% and 38%, respectively. TRM was 0%. Most common toxicities included: fever(67%), mucositis(46%), infections(46%), diarrhea(42%) and cardiac arrhythmias(18.2%) [all CTC grade 1–2]. Grade 3–4 toxicities were uncommon and included: myocardial infarction(6%), diarrhea(3%) and mucositis(3%). Overall, cardiac toxicities were more frequent than expected. The relationship between pre-ASCT parameters (e.g. isotype, lab values at transplant, co-morbidities and number of stem cells collected) and outcomes (e.g. PFS, OS, grade 3–4 toxicities) were assessed by univariate analysis. A higher number of CD34 cells harvested correlated with shorter days to neutrophil and platelet engraftment (p<0.0008) and prolonged PFS (p=0.043). Pts with IgA vs. IgG or other subtypes had a shortened PFS post-transplant (p=0.003). No significant predictors of OS or grade 3–4 toxicities were identified. Summary: Our preliminary data suggest that ASCT is feasible and generally well-tolerated in selected elderly (≥ 70 yrs) MM pts. Although toxicities, in particular cardiac, appear more common in this population, PFS and OS are comparable to that in younger pts and TRM was not elevated. We support consideration of very elderly pts for ASCT but encourage careful co-morbidity screening pre-transplant.

High-Dose Cytoxan, Etoposide, and Cisplatin Followed by Autologous Hematopoietic Cell Transplantation for the Treatment of Hodgkin Lymphoma: A 20-Year Single-Institutional Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1913-1913
Author(s):  
Thomas R. Klumpp ◽  
Moshe C. Chasky ◽  
Robert V. Emmons ◽  
Mary E. Martin ◽  
James L. Gajewski ◽  
...  
Keyword(s):  
Complete Remission ◽  
Total Dose ◽  
Hodgkin Lymphoma ◽  
Pulmonary Toxicity ◽  
Median Number ◽  
High Dose ◽  
Post Transplant ◽  
Grade 3 ◽  
Active Disease

Abstract Since 1988 we have treated 66 patients with relapsed, refractory, or high-risk Hodgkin lymphoma (HD) with high-dose CEP consisting of cyclophosphamide 1,500 mg/m2/day × 4 (total dose, 6,000 mg/m2), etoposide 400 mg/m2 twice daily × 6 doses (total dose, 2,400 mg/m2), and cisplatin 50 mg/m2/day × 3 by continuous i.v. infusion (total dose 150 mg/m2) followed by infusion of autologous peripheral blood stem cells (n=49), bone marrow (n=16), or both (n=1). The patient population included 41 males and 25 females. The median age at transplant was 33 years (range, 17–64 years). Twenty-three patients (35%) had never achieved complete remission prior to transplant, 36 (55%) had previously achieved a complete remission but subsequently relapsed, and 3 (5%) were in first complete remission. Information regarding the disease status at transplant was unavailable for 4 patients (6%). Twenty-seven patients (41%) remain alive and free of any post-transplant relapse or progression as of the most recent follow-up, and an additional 10 patients (15%) manifested active disease post-transplant but are currently in remission following additional post-transplant therapy, yielding a total of 37 patients (56%) currently in CR. In addition, 5 patients (8%) remain alive with active disease, 23 patients (35%) died of progressive disease, and only 2 patients (3%) died of treatment-related causes including diffuse alveolar hemorrhage (1 patient) and hepatic veno-occlussive disease (1 patient). With a median follow-up of 4.4 years among surviving patients, the Kaplan-Meier 5-year estimates for event-free survival and overall survival are 34% and 60%, respectively, and five-year survival was superior among patients who had achieved at least one CR prior to transplant versus patients who had never been in CR prior to transplant (71% versus 43%, p = 0.03). Detailed adverse events data is available regarding all patients transplanted since September 1996: Of these, only 3 (7%) suffered grade 3 or greater pulmonary toxicity, 12 (29%) exhibited grade 3 or higher mucositis, and 10 (24%) had grade 3 or higher nausea or vomiting. The median number of days from transplant to neutrophil recovery (500 cells/uL) was 10 days, whereas the median number of days to platelet recovery (20,000 cells/uL) was 12 days. We conclude that high- dose CEP followed by autologous transplant is an active and well-tolerated treatment program in patients with relapsed or refractory HD. The low incidence of pulmonary toxicity is noteworthy given that a high percentage of patients had been exposed to bleomycin and/or thoracic XRT prior to transplant, and appears to be superior to that reported with conventional CBV-conditioned transplants in patients with HD.

High Dose Melphalan with Autologous Stem Cell Transplantation Overcomes Poor Prognosis of Primary Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1350-1350
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Plasma Cells ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hematologic Response ◽  
Bone Marrow Plasma ◽  
Organ Response ◽  
High Dose Melphalan

Abstract Abstract 1350 Background: Systemic Primary AL Amyloidosis is a rare but potentially fatal disease resulting from tissue deposits of amyloid fibrils derived from monoclonal immunoglobulin light chains. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) is associated with hematologic and organ responses and improved survival. Methods: In this retrospective analysis we identified 46 patients with primary AL amyloidosis who received auto HCT between 01/1998 to 05/2010 at MDACC. Organ responses were determined using Amyloidosis Consensus Criteria. Results: The median age at auto HSCT was 56 years (34-74) where 61% were males and 35% were older than 60 years of age. 61% had lambda light chain restriction and only 4% had cytogenetic abnormalities. Disease characteristics are summarized in Table 1. The median time from diagnosis to auto HCT was 6.6 months (2.2-29.4 months). 22 pts (47.8%) had one organ, 19 pts (41.3%) had 2 organ and 4 pts (8.7%) had 3 organ involvement. 11 pts (23.9%) had heart and 35 pts (76.1%) had kidney involvement. The median follow up from the time of diagnosis was 22.4 months and from time of auto HCT was 16.7 months. High dose Melphalan dose was 200mg/m2 in 24 pts (52%) and 140mg/m2 in 22 (47.8%). There were 4 early deaths and 4 pts whose follow up was less than 3 months and their response was not assessed. Out of the 38 evaluable patients, the post-transplant organ responses were as follows ≥PR 25(66%), ≥stable disease 35(92%) (Table2). The hematologic responses were: CR=5 (13%), ≥VGPR=10(26%), ≥PR=26 (68%), ≥SD=37(97%). One patient had progressive disease. There was a correlation between organ response and hematologic response (chi square;p<10-3). The day-100 treatment related mortality (TRM) was 8.7% and 1-yr TRM was 13%. The median progression-free (PFS) and overall survival (OS) from auto HCT was 73.8 months and not reached (from transplant). The median PFS and OS from diagnosis were 93 months and 59.8 months respectively. In multivariate analysis, heart involvement (p=0.01), female sex (p=0.011), age ≥60 years (p=0.002), bone marrow plasma cells≥10% (p=0.043) and Beta-2 microglobulin>3.5mg/l (p=0.02) were associated with poor OS. Improved OS correlated with organ response (52.6 vs 11.4 months; p=0.01) and hematologic response (52.6 vs.6.1months; p=0.002). Hemoglobin <10 g/dl (p=0.047), bone marrow plasma cells≥10% (p=0.043) and age≥60 years (p=0.075) were associated with shorter PFS. Hematologc response (p=0.48) and organ response (p=0.12) were not associated with improved PFS. Conclusion: In this analysis the outcome of patients with primary systemic AL amyloidosis was durable with auto HCT with acceptable mortality risk and improved survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Bortezomib Maintenance Therapy after Induction with R-CHOP, ARA-C and Autologous Stem Cell Transplantation in Newly Diagnosed MCL Patients, Results of a Multicenter Phase II HOVON Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 339-339 ◽  
Author(s):  
Jeanette K Doorduijn ◽  
Monique C. Minnema ◽  
Marie Jose Kersten ◽  
Pieternella J Lugtenburg ◽  
Martin R. Schipperus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Research Funding ◽  
Progressive Disease ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Introduction. The standard first-line treatment of young and fit mantle cell lymphoma (MCL) patients consists of a rituximab containing induction of CHOP and high dose ARA-C, followed by high dose consolidation and autologous stem cell transplant (ASCT). Thus far, almost all patients relapse after ASCT. Bortezomib is a proteasome inhibitor with activity in MCL. We investigated in a randomized phase II study whether there was any indication that maintenance therapy with bortezomib after ASCT could improve the outcome of treatment, measured as event free survival (EFS). Methods. Patients 18-65 years with newly diagnosed MCL were treated with 3 cycles of R-CHOP and 2 cycles of ARA-C (2 x 2 g/m2 iv d1-4) and rituximab (375 mg/m2, iv d11). Patients in PR or CR continued with ASCT after BEAM conditioning. Patients with a PR or CR after ASCT, with a neutrophil count > 0.5 x 109/l and platelets > 80 x 109/l were randomized between bortezomib and no further treatment. Bortezomib 1.3 mg/m2 iv was given once every two weeks, for 2 years, starting between 6 - 12 weeks after transplantation. Results . Between October 2007 and February 2012, 140 patients aged 34-66 years (median 57) were registered. Five patients were not eligible. The MIPI score was low, intermediate, high or unknown in 57%, 32%, 10% and 1% respectively. All eligible patients started induction treatment with R-CHOP. Two patients did not receive the first ARA-C cycle, because of progressive disease and physician decision. Hundred-fifteen patients (85%) received the BEAM and ASCT. Reasons to stop protocol treatment before ASCT were: progressive disease (PD) (n=6), inadequate stem cell harvest (n=3), excessive toxicity (n=3), other reasons (n=8). The response after ASCT was CR/CRu in 99 patients (86%), PR in 15 (13%), unknown in 1 (1%). Only 62 patients (45%), aged 34-65 years (median 56) were randomized between bortezomib maintenance and no further treatment. Two patients were randomized, but not eligible. Reasons for no randomization were: not eligible (n=30), patient refusal (n=14), excessive toxicity (n=2, and other reasons (n=7). In each treatment arm 30 patients were included. The patient characteristics were well balanced, except the MIPI score. In the no maintenance arm 21 patients (70%) had a low MIPI, compared to 15 patients (50%) in the bortezomib arm, and 6 (20%) versus 11 (37%) patients had an intermediate MIPI score. In both arms 3 patients (10%) had a high MIPI. Fifteen patients (50%) in the maintenance group continued bortezomib for 2 years. Reasons to stop earlier were excessive toxicity (n=6), PD/relapse (n=4), patients refusal (n=3) and other (n=2). The main adverse events during maintenance therapy were neurologic (CTC grade 2: 14%, grade 3: 4%), and infectious (grade 2: 11%, grade 3: 7%). Three patients developed a secondary malignancy: a basal cell carcinoma in the no maintenance group, a melanoma and a prostate carcinoma in the bortezomib group. With a median follow-up of the patients still alive of 50.9 months EFS at 4 years for all patients is 61%, and the overall survival (OS) 78%. The median follow-up of the randomized patients still alive is 42.9 months. The EFS at 4 years is 72% without maintenance versus 71% in the patients randomized for bortezomib maintenance. The OS at 4 years also shows no significant difference between the groups, 90% versus 93% respectively. Conclusion. There is no indication that bortezomib iv maintenance in a frequency of once every 2 weeks does improve the EFS of newly diagnosed MCL patients after intensive induction treatment with R-CHOP, double ARA-C and BEAM followed by ASCT. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Doorduijn: Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Off Label Use: bortezomib maintenance in MCL. Minnema:Celgene: Consultancy; Jansen Cilag: Consultancy; Amgen: Consultancy. Kersten:janssen: Honoraria, Research Funding; takeda millennium: Research Funding; roche: Honoraria, Research Funding. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Schipperus:Novartis: Consultancy. Zijlstra:Celgene: Consultancy; Roche: Consultancy.

NCOG-36. LONG-TERM SURVIVAL AND COGNITIVE FUNCTION FOLLOW UP OF PRIMARY CNS LYMPHOMA TREATED WITH R-MVP FOLLOWED BY HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANT CONSOLIDATION

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi159-vi160
Author(s):  
Kate Therkelsen ◽  
Christian Grommes
Keyword(s):  
Stem Cell ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Consolidation Therapy ◽  
Term Survival ◽  
Stem Cell Rescue ◽  
Long Term Follow Up

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare central nervous system malignancy, and long-term follow up studies are uncommon. First line therapy is based on high-dose methotrexate and different consolidation therapy options. This is a long-term follow up study of PCNSL patients enrolled in a prospective trial using R-MPV chemotherapy regimen followed by high dose chemotherapy and autologous stem cell rescue to determine long-term survival and cognitive effects. METHODS From June 2005 to September 2011, 32 newly diagnosed immunocompentent PCNSL were enrolled. Patients received 5-7 doses of rituximab (500mg/m2), methotrexate (3.5 gm/m2), procarbazine (100mg/m2), and vincristine (1.4mg/m2) (R-MVP). Consolidation therapy consisted of high dose chemotherapy (HDC) with thiotepa (250 mg/m2), busulfan (3.2 mg/kg), and cyclophosphamide (60 mg/kg), followed by autologous stem cell rescue (ASCT) in those with partial or complete response to R-MVP. Long-term follow-up status including disease status, cognitive status (KPS, NANO score), and leukoencephalopathy (modified Fazkas Scale) were collected. RESULTS 26 of 36 underwent HDC and ACST. Of those, 3 died due to treatment related effects; 2 died of disease progression within two years after ASCT. After a median follow-up of 10.5 years, none of the remaining 21 patients progressed. At the time of last follow up, the median KPS was 90, compared to 80 at time of ASCT. The median NANO score and leukoencephalopathy score post ASCT and at follow-up did not change. Of note, 2 of 4 patients with a partial or complete response to R-MVP that elected not to proceed with HDC-ASCT consolidation, experienced progression at a mean of 52 months. CONCLUSION Long-term follow up demonstrates that treatment was tolerated well with stable leukoencephalopathy on MRI and good performance status. Disease recurrence 2 years after HDC with ASCT consolidation was not observed.

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.

A Phase II Study of Myeloablative I-131-Anti CD-20 (Tositumomab) Radioimmunotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Adults ≥60 Years of Age with High-Risk Relapsed or Refractory B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 487-487 ◽  
Author(s):  
Ajay K. Gopal ◽  
Joseph G. Rajendran ◽  
Ted A. Gooley ◽  
John M. Pagel ◽  
Darrell R. Fisher ◽  
...  
Keyword(s):  
Older Adults ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Phase Ii ◽  
High Dose ◽  
Grade 3

Abstract The majority of patients with relapsed or refractory B-cell, non-Hodgkin’s lymphoma (NHL) are over 60 years of age, yet many are denied potentially curative high-dose regimens due to concerns of excessive toxicity with stem cell transplantation in this age group. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be ideal for older adults requiring high-dose therapy. We have treated 24 patients with relapsed or refractory B-cell NHL aged ≥60 years using high-dose I-131-tositumomab (GlaxoSmithKline) and ASCT on a phase II trial. Patients were required to have a performance status of 0–1, acceptable organ function, ≥2x106 CD34+ cells/kg collected, and &lt;20 Gy prior radiation to critical organs. Patients with splenomegaly or tumor bulk over 500cc were required to undergo further cytoreduction or splenectomy in order to optimize biodistribution of the radiolabeled antibody. Patients without evidence of disease at the time of therapy were excluded. All pts underwent outpatient dosimetry using tositumomab (1.7 mg/kg) labeled with 5–10mCi I-131 followed by serial quantitative gamma camera imaging and patient and organ-specific dosimetry. Patients then received individualized infusions of I-131-tositumomab (1.7 mg/kg) to deliver 25–27Gy to the critical normal organ receiving the highest radiation dose followed by ASCT. Between 12/1/99 and 4/29/05 24 pts were enrolled on this study. Baseline characteristics included: median age at ASCT = 64 yrs (range 60–76 yrs), male = 15/24, median number of prior regimens = 4 (range 2–14), chemoresistant disease (defined as &lt; a partial response to the most recent regimen) = 13/24, Stage III/IV=100%, &gt;1 extranodal site = 21%, elevated LDH at treatment = 46%, IPI score at transplant 3–5 = 46%, Histology: diffuse large B-cell (DLBCL)=9 pts (with 4/9 transformed from follicular lymphoma [FL]), mantle cell (MCL)=8 pts, FL=6 pts, and marginal zone (MZL) 1 pt. The median I-131 activity administered was 525 mCi (range 328–1154 mCi) with dose limiting organs being lung, liver, and kidney in 12, 8, and 4 patients, respectively. The therapy was well tolerated with no treatment-related deaths, and no grade 3–4 Bearman toxicity. NCI CTC non-hematopoeitic toxicities by day 100 included: Grade 4=2/24 and Grade 3=17/24. The median time after ASCT for recovery of platelets &gt; 20K and neutrophils &gt;500 was 10 and 15 days, respectively. Sixteen of 24 pts remain alive (67%) and 10 (42%) are alive and progression-free with a median follow up from ASCT of 2.2 yrs (range 1 mo.–4.9 yrs.) for survivors. The estimated 3-year overall and progression-free survival are 56% and 37%, respectively. Surviving patients include 6/8 with MCL, 5/7 with FL/MZL, and 5/9 with DLBCL as well as 9/13 with chemoresistant disease. Myeloablative I-131-tositumomab with ASCT is a well-tolerated and effective transplant option for older adults with high-risk, relapsed B-NHL, though longer follow-up and additional pts will be needed to confirm the reproducibility and durability of these findings.

Long-Term Follow Up of High-Dose Chemotherapy With Autologous Stem Cell Rescue in Adults With Ewing Tumor

2005 ◽  
Vol 28 (3) ◽  
pp. 301-309 ◽  
Author(s):  
Val??rie Laurence ◽  
Jean-Yves Pierga ◽  
Sophie Barthier ◽  
Antoine Babinet ◽  
Claire Alapetite ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Long Term Follow Up ◽  
Autologous Stem Cell Rescue ◽  
Ewing Tumor

High-dose cyclophosphamide for refractory autoimmune hemolytic anemia

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 704-706 ◽  
Author(s):  
Victor M. Moyo ◽  
Douglas Smith ◽  
Isadore Brodsky ◽  
Pamela Crilley ◽  
Richard J. Jones ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Hemolytic Anemia ◽  
Absolute Neutrophil Count ◽  
Autoimmune Hemolytic Anemia ◽  
High Dose ◽  
Safety And Efficacy ◽  
Stem Cell Rescue ◽  
Age And Sex

Abstract High-dose cyclophosphamide, without stem cell rescue, has been used successfully to treat aplastic anemia and other autoimmune disorders. To determine the safety and efficacy of high-dose cyclophosphamide among patients with severe refractory autoimmune hemolytic anemia, we treated 9 patients with cyclophosphamide (50 mg  ·  kg−1  ·  d−1 for 4 days) who had failed a median of 3 (range, 1-7) other treatments. The median hemoglobin before treatment was 6.7 g/dL (range, 5-10 g/dL). The median time to reach an absolute neutrophil count of 500/μL or greater was 16 days (range, 12-18 days). Six patients achieved complete remission (normal untransfused hemoglobin for age and sex), and none have relapsed after a median follow-up of 15 months (range, 4-29 months). Three patients achieved and continue in partial remission (hemoglobin at least 10 g/dL without transfusion support). High-dose cyclophosphamide was well tolerated and induced durable remissions in patients with severe refractory autoimmune hemolytic anemia.

scholarly journals MBCL-29. PHASE I/II STUDY OF SEQUENTIAL HIGH-DOSE CHEMOTHERAPY WITH STEM CELL SUPPORT IN CHILDREN YOUNGER THAN 5 YEARS OF AGE WITH HIGH-RISK MEDULLOBLASTOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii394-iii395
Author(s):  
Christelle Dufour ◽  
Julien Masliah-Planchon ◽  
Marie-Bernadette Delisle ◽  
Anne Geoffray ◽  
Rachid Abbas ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Phase I ◽  
Complete Response ◽  
Multicenter Trial ◽  
High Dose Chemotherapy ◽  
Craniospinal Irradiation ◽  
High Dose ◽  
Stem Cell Rescue

Abstract PURPOSE To assess the 3-year EFS rate of children younger than 5 years of age with high-risk medulloblastoma (MB) treated according to the prospective multicenter trial HR MB-5. PATIENTS AND METHODS After surgery, all children received 2 cycles of Etoposide- Carboplatine. If partial (PR) or complete response (CR) was achieved after induction chemotherapy, children received 2 courses of thiotepa (600mg/m²) with stem cell rescue. For patients in CR after high-dose chemotherapy, they received one course of Cyclophosphamide – Busilvex with stem cell rescue (Phase I part). The others patients (not in PR after induction or in CR after thiotepa) were treated with 2 cycles of Temozolomide-Irinotecan followed by age-adapted craniospinal irradiation and maintenance treatment. RESULTS 28 children (2 to 4 years; median: 3.0 years) were enrolled. Group 3 MB were most common (57%). The response rate to Etoposide-Carboplatine was 60.7%. Among 20 patients treated with Thiotepa, 13 children were in CR and received Cyclophosphamide – Busilvex without radiotherapy. Out of them, 9 patients (45%) are alive in CR without craniospinal irradiation (median follow-up 5 years). Among 15 patients treated with radiotherapy, 8 patients are alive (median follow-up 3.8 years). The study was prematurely stopped for an excess of events. The median follow-up was 4 years (range 1.5 - 6.1). The 3-year EFS and OS were 42.3% [25.9 - 60.6] and 71.3% [52.7 - 84.7], respectively. CONCLUSIONS This risk-adapted strategy did not improve EFS in young children with high-risk MB. However, the study shows that good responders to chemotherapy can be cured without recourse to irradiation.

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