Rituximab in Anti-Mag Associated Neuropathy : A Monocentric Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4909-4909
Author(s):  
Richard Delarue ◽  
Benedicte Deau ◽  
Marie-Alexandra Alyanakian ◽  
Bruno R. Varet ◽  
Olivier Hermine
Keyword(s):  
Stem Cell ◽  
Case Reports ◽  
Alkylating Agents ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Mild Improvement ◽  
Sensory Motor ◽  
Anti Cd20 ◽  
High Dose Melphalan ◽  
Monoclonal Component

Abstract Anti-MAG associated neuropathy is a rare disorder characterized by a sensory-motor polyneuropathy in the context of monoclonal IgM, which activity is directed against myelin-associated glycoprotein on the surface of myelin sheaths. Treatments are usually ineffective. Most common therapy is based on alkylating agents such as Chlorambucil, which however only rarely improve neurological tests nor induce disappearance of monoclonal component. More recently, the benefit of monoclonal anti-CD20 antibody Rituximab was reported in case reports. Thus, we have performed since 2002 a prospective pilot study to assess the benefit of Rituximab in anti-MAG associated neuropathy. We report here the first four successive patients treated. Patients and Methods : inclusion criteria were as follow : peripheral sensory-motor polyneuropathy with clinical and electrophysiological symptoms compatible with anti-MAG associated neuropathy; serum monoclonal IgM; serum anti-MAG reactivity; absence of other cause of peripheral neuropathy such as amyloidosis; absence of underlying condition contra-indicating Rituximab therapy. Patients received 4 courses of Rituximab (375 mg/m2) with a 7 days interval between two infusions. Usual premedication with corticosteroids and paracetamol were administered. Evaluation of clinical, biological and immunochemical efficiency was performed every three months. Results : characteristics of the first four patients treated are as follow : 3 males and 1 female; median age : 65 years (57 – 87); median time between onset of symptoms and Rituximab therapy : 4 years (3 – 6). Previous treatments were Chlorambucil (3/4), corticosteroids (2/4), intravenous Ig (1/4), anthracyclin-containing regimen (1/4), plasmapheresis (1/4). All were ineffective. Rituximab was well tolerated by all patients. Median follow-up after treatment is 2 years (1 – 3). None of the patients exhibit improvement of clinical neurological symptoms. Electrophysiological evaluation show only a mild improvement in 1 patient. Moreover, no decrease in monoclonal component nor disappearance of anti-MAG reactivity of serum were observed in any cases. Interestingly, one patient exhibited later neurological and biological improvement after high dose Melphalan followed by autologous stem cell transplantation. Conclusion : Rituximab monotherapy does not seem to improve neurological outcome of patients with anti-MAG polyneuropathy as well as is unable to clear serum from monoclonal IgM. Therefore, new approaches are needed, for example with high dose chemotherapy with stem cell support in selected patients.

scholarly journals Myeloablative Anti-CD20 Radioimmunotherapy +/- High-Dose Chemotherapy Followed by Autologous Stem Cell Support for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival

Oncotarget ◽  
2013 ◽  
Vol 4 (6) ◽  
pp. 899-910 ◽  
Author(s):  
Julia Y Wagner ◽  
Kathleen Schwarz ◽  
Susanne Schreiber ◽  
Burkhard Schmidt ◽  
Hans-Jürgen Wester ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Term Survival ◽  
Stem Cell Support ◽  
Anti Cd20 ◽  
Cell Support

Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2234-2239 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Giovanni Martinelli ◽  
Elena Zamagni ◽  
Maria Rosa Motta ◽  
Simonetta Rizzi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Reconstitution ◽  
Cd34 Cells ◽  
Preparative Regimen ◽  
Total Body ◽  
High Dose Melphalan

Eighty-two patients with advanced multiple myeloma (MM) were enrolled in 2 sequential clinical studies of 1 or 2 courses of myeloablative therapy with stem cell support. Conditioning regimens consisted of high-dose melphalan (MEL) with or without total body irradiation (TX1 = 35) and MEL as the first preparative regimen, followed within 6 months by busulfan and melphalan (TX2 = 47). On the basis of adequate stem cell harvest, 31 patients (TX1 = 13; TX2 = 18) were transplanted with highly purified CD34+ cells. Positively selected stem cells did not adversely affect hematopoietic reconstitution compared with unmanipulated peripheral blood stem cell. Overall, the complete remission (CR) rate of evaluative patients was 13.8% and 41% for single and double autotransplant, respectively (P = .04). Moreover, 3 patients undergoing TX2 achieved molecular remission and 2 remain PCR-negative after 36 and 24 months from autograft. The median event-free survival (EFS) durations for TX1 and TX2 were 17 and 35 months, respectively (P = .03). Actuarial 3-year overall survival for patients treated with 1 or 2 transplants are 76% and 92%, respectively (P = NS). On multivariate analysis, superior EFS was associated with low β2 microglobulin (β2-M) level at diagnosis and TX2, whereas overall survival was correlated with β2-M. Positive selection of CD34+ cells did not influence the achievement of clinical or molecular CR, as well as remission duration or survival of MM patients. Thus, whereas multiple cycles of high-dose therapy may be beneficial for patients with myeloma, the clinical impact of tumor cell purging remains highly questionable.

t(4;14) Positive Multiple Myeloma Is Chemosensitive to Dexamethasone and/or Thalidomide but Not Alkylating Agents: Rapid Relapse and Not Primary Drug Resistance Explains Poor Outcomes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2417-2417
Author(s):  
Wilfrid J. Jaksic ◽  
Suzanne Trudel ◽  
Hong Chang ◽  
Xi Qi ◽  
Joseph R. Mikhael ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Stem Cell ◽  
Induction Chemotherapy ◽  
Stable Disease ◽  
Alkylating Agents ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Primary Drug Resistance ◽  
High Dose Melphalan ◽  
Primary Drug

Abstract The t(4;14) simultaneously dysregulates expression of fibroblast growth factor receptor 3 (FGFR-3) and MMSET and has been detected in 15% of MM patients. Despite being an early event in the genesis of clonal gammopathy the t(4;14) is somewhat surprisingly reported as a poor prognostic factor in patients treated with both conventional chemotherapy and those undergoing autologous stem cell transplantation (ASCT). Presumably either primary drug resistance or, alternatively, rapid relapse following treatment must explain this outcome. To address this clinical issue we analyzed 128 patients who were treated with induction chemotherapy followed by melphalan 200 mg/m2 at our institution between 1998–2000. Using FISH analysis we identified 16 of these patients with a t(4;14). These patients had a predominance of the IgA isotype (56.3%) compared with t(4;14) negative patients (17.7%) (p = 0.0019). Otherwise baseline characteristics including sex, age, B-2 microglobulin, CRP, calcium, creatinine, Hb, albumin or percentage of bone marrow plasma cells were indistinguishable from the general MM poulation. Fifteen t(4;14) patients received induction chemotherapy with 4–5 cycles of vincristine, adriamycin and dexamethasone(VAD) with one receiving pulsed dexamethasone alone. Thirteen of the sixteen (81%) responded with > 50% paraprotein decrease. However 3 of these 13 patients demonstrated early progression of disease during later cycles of VAD or during stem cell collection and required further salvage prior to ASCT. Use of high dose melphalan and ASCT resulted in a further 54% of patients achieving a >50% paraprotein decrease with a mean paraprotein reduction of 49% (range 0–99%). Nevertheless the median progression free survival (PFS) post ASCT was only 9.9 months, significantly shorter than for t(4;14) negative patients (p=0.0001). Given the surprisingly short PFS following high dose alkylating agents we next examined all salvage regimens employed. Ten patients at some point received a conventional dose alkylating agent as salvage (cyclophosphamide or melphalan). Response was dismal with stable disease in 6 patients and progressive disease in 4 patients. In contrast 14 patients at some point received salvage thalidomide or high dose dexamethasone either as a single agent or in combination. Five patients demonstrated a partial response (>50–90% reduction), 4 patients a minor response and 5 patients had stable disease for an overall response rate of 64%. Two patients treated with Bortezomib demonstrated partial responses. We conclude from this preliminary analysis that t(4;14)+ve MM is poorly responsive to alkylating agents, including high dose melphalan and thus that use of these agents (including ASCT) is generally of no long term value in this patient population. Given the high response rates of 81% at induction and 64% at salvage, induction and maintenance regimens containing high dose dexamethasone and/or thalidomide are favored. Nevertheless, since response to these agents is often short lived novel therapeutic regimens are required. In this regard the early clinical study of targeted FGFR-3 tyrosine kinase inhibitors which have shown pre-clinical promise is encouraged.

High-Dose Topotecan, Melphalan and Cyclophosphamide (TMC) with Autologous Stem Cell Support for Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4452-4452
Author(s):  
Syed MA Kazmi ◽  
Floralyn L Mendoza ◽  
Donna Weber ◽  
Michael L Wang ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Chromosomal Abnormalities ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Refractory Disease ◽  
Standard Regimen ◽  
First Remission ◽  
High Dose Melphalan

Abstract Introduction High dose chemotherapy and autologous stem cell transplantation (auto SCT) was associated with prolonged event-free (EFS) and overall survival (OS) in selected patients with multiple myeloma (MM) in at least two randomized controlled trials. High-dose melphalan at 200 mg/m2 is considered the standard regimen, but the complete remission (CR) rate at best is 30–40% and the EFS approximately 2 years. Novel preparative regimens are being evaluated to improve the efficacy without increasing the toxicity. We evaluated the safety and efficacy of a new regimen, Topotecan, Melphalan and Cyclophosphamide (TMC) in patients undergoing auto SCT for MM. Methods The primary objectives were to determine the safety and to evaluate if TMC could increase the CR rate in MM patients undergoing auto SCT. Patients received cyclophosphamide at the dose of 1 g/m2 intravenously over 2 h on days -6, -5, -4; melphalan at the dose of 70 mg/m2 intravenously over 30 min on days -3 and -2 and topotecan at a dose of 3.5 mg/m2 over 30 min for 5 total doses on days -6 to -2. Results 44 patients (26 males, 18 females) with primary refractory disease or in first remission received the TMC regimen followed by auto SCT between August 2002 and March 2004. The median age of patients at auto SCT was 55 years (range 40–67) and the median interval between the diagnosis and auto SCT was 6.3 month (range 2.2– 42 months). Twelve patients (27%) had chromosomal abnormalities on conventional cytogenetic studies. Median follow-up in surviving patients was 47.8 months. Median time to neutrophil engraftment (ANC > 500/dl) and platelet engraftment (>20,000/dl) were 10 (range 7–11 days) and 9 days (range 6–9 days), respectively. Thirty seven patients (84%) were transplanted for consolidation of first remission and 7 for primary refractory disease (16%). Most common adverse events were: grade 1& 2 nausea (59%), grade 1 & 2 diarrhea (41%) and dysphagia (34%). Non-hematologic grade 3 & 4 toxicities were seen in 9 patients (20%) and included infectious complications (2 patients), congestive heart failure exacerbation (2 patients), electrolyte abnormalities including hypocalcemia and hypokalemia (1 patient each), GI complications like dysphagia and vomiting (1 patient each) and cardiac arrhythmia (1 patient). Febrile neutropenia occurred in 8 patients (18%). Thirty-three patients (75%) had a complete or partial response, 9 patients (21 %) had a minimal response or stable disease, while 2 patients had progressed within 3 months of auto SCT. At the time of this analysis, 31 patients are alive, 13 of whom in remission. Four-year EFS was 23.5%, and 4-year OS was 63%. Patients with chromosomal abnormalities had a shorter time to progression (13.9 vs. 19.7 months, p=0.18) that was not statistically significant. These results were similar to those reported by our group in 89 patients who received high-dose mephalan (200 mg/m2) only: complete + partial response rate of 66%; 4-year Kaplan-Meier estimates of EFS and OS 20% and 57%, respectively. (Anagnostoupoulos et al. Cancer 2004). Conclusion TMC is a safe preparative regimen for auto SCT for MM. There is no major advantage over high-dose melphalan alone in terms of CR rate or EFS in patients in first remission or primary refractory disease.

Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2234-2239 ◽  
Author(s):  
Roberto M. Lemoli ◽  
Giovanni Martinelli ◽  
Elena Zamagni ◽  
Maria Rosa Motta ◽  
Simonetta Rizzi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Reconstitution ◽  
Cd34 Cells ◽  
Preparative Regimen ◽  
Total Body ◽  
High Dose Melphalan

Abstract Eighty-two patients with advanced multiple myeloma (MM) were enrolled in 2 sequential clinical studies of 1 or 2 courses of myeloablative therapy with stem cell support. Conditioning regimens consisted of high-dose melphalan (MEL) with or without total body irradiation (TX1 = 35) and MEL as the first preparative regimen, followed within 6 months by busulfan and melphalan (TX2 = 47). On the basis of adequate stem cell harvest, 31 patients (TX1 = 13; TX2 = 18) were transplanted with highly purified CD34+ cells. Positively selected stem cells did not adversely affect hematopoietic reconstitution compared with unmanipulated peripheral blood stem cell. Overall, the complete remission (CR) rate of evaluative patients was 13.8% and 41% for single and double autotransplant, respectively (P = .04). Moreover, 3 patients undergoing TX2 achieved molecular remission and 2 remain PCR-negative after 36 and 24 months from autograft. The median event-free survival (EFS) durations for TX1 and TX2 were 17 and 35 months, respectively (P = .03). Actuarial 3-year overall survival for patients treated with 1 or 2 transplants are 76% and 92%, respectively (P = NS). On multivariate analysis, superior EFS was associated with low β2 microglobulin (β2-M) level at diagnosis and TX2, whereas overall survival was correlated with β2-M. Positive selection of CD34+ cells did not influence the achievement of clinical or molecular CR, as well as remission duration or survival of MM patients. Thus, whereas multiple cycles of high-dose therapy may be beneficial for patients with myeloma, the clinical impact of tumor cell purging remains highly questionable.

scholarly journals High-Dose Melphalan Versus Busulfan, Cyclophosphamide As Conditioning Regimens for Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2001-2001
Author(s):  
Michael Styler ◽  
Pamela Ann Crilley ◽  
Maneesh Jain ◽  
Kristine Ward ◽  
David Topolsky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
University Hospital ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Conditioning Regimens ◽  
High Dose Melphalan

Abstract Introduction: Autologous stem cell transplantation after high dose chemotherapy has been shown to increase survival in patients with multiple myeloma. Studies have shown prolongation of median overall survival by 12 months. The standard conditioning regimen is high-dose Melphalan (HDM) at a dose of 200 mg/m2. Melphalan was shown to be superior to Thiotepa when given with total body irradiation. Other regimens include high dose Carboplatin with Etoposide and Cyclophosphamide or Cyclophosphamide, Carmustine and Etoposide. No regimen has shown marked superiority over others. Patients of I. Brodsky Associates at Hahnemann University Hospital were treated with autologous transplant with either high-dose Melphalan (HDM) or Busulfan and Cyclophosphamide (BuCy) as the conditioning regimens. To date, no studies comparing these two preparative regimens have been published. Thus the purpose of our chart review was to compare progression free survival of the two regimens. Hypothesis: The objective of the study is to determine if there is a difference in progression free survival and side effects in autologous stem cell transplant patients receiving either Melphalan or Busulfan and Cyclophosphamide as conditioning regimens. Methods: This study is a retrospective chart review of 94 patients, who underwent HSCT for multiple myeloma at Hahnemann University Hospital between December, 1989 and March, 2012. 47 patients received BuCy (Busulfan 16mg/kg and Cyclophosphamide 120mg/kg) and 49 patients received Melphalan 200 mg/m2. The primary end points were progression free survival (PFS) at 6 months, one year and overall PFS. Data was analyzed using the Kaplan Meier method with the WINKS SDA6 statistical software. Survival curves were compared using the Mantel-Haenszel comparison. Secondary study endpoints included safety profile. Results: Median age was 56 and 60 for the BuCy and HDM groups, respectively. The BuCy group had 68% males while the HDM group had 53% males. Patients in both groups received peripheral stem cell transplants with the exception of 4 in the BuCy group who had bone marrow transplants. As compared with BuCy, HDM treatment increased median progression free survival (37.3 vs. 18.1 months; P=0.014). There was a significantly higher rate of 6 month progression free survival (94% vs. 75%; P=.011) and 12 month progression free survival (82% vs 57%; P=0.006) in the HDM group compared to the BuCy group. The safety profile was as follows comparing BuCy and HDM, respectively: Moderate/severe mucositis (55% vs 48%), VOD (2 of 49 vs 1 of 47), hemorrhagic cystitis (2 of 49 vs. 1 of 47), infection within 100 days of transplant (28% vs 18%), mean peak T. Bilirubin ( 0.75 vs. 0.89), mean peak Alkaline phosphatase (127 vs. 90), mean peak AST (37.5 vs. 35), mean peak Cr (1.0 vs 1.2), mean days to ANC of 1000 (11.9 vs. 12.5), mean days to platelets > 20K (11.3 vs. 9.9), mean days to platelets > 50K (13.5 vs. 12.9). Conclusion: Our study showed that median progression free survival was longer with the HDM group compared to the BuCy group overall and at 6 and 12 months. Overall, patients treated with HDM had a median improvement in DFS of 1.5 years (37.3 months vs. 18.1 months, p=0.014). This data supports the use of HDM as the effective first line regimen for high dose chemotherapy and autologous stem cell transplant for patients with multiple myeloma. A limitation to our study is incomplete data regarding maintenance therapy post-transplant for the two groups. There was one patient in the BuCy group who relapsed at 236 months. Such prolonged disease free survival was not apparent in the HDM group but the median time to follow up for BuCy is longer by up to 13 years. BuCy was associated with more infections and more severe mucositis, while metabolic and hematologic toxicities were similar in both groups. Disclosures No relevant conflicts of interest to declare.

High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: Past or future?

2001 ◽  
Vol 28 (4) ◽  
pp. 377-388 ◽  
Author(s):  
Roy D. Baynes ◽  
Roger D. Dansey ◽  
Jared L. Klein ◽  
Caroline Hamm ◽  
Mark Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem

PROSPECTS FOR HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE FIRST LINE OF THERAPY FOR AGGRESSIVE NON-HODGKIN’S LYMPHOMAS

2017 ◽  
Vol 63 (2) ◽  
pp. 326-328
Author(s):  
Larisa Filatova ◽  
Yevgeniya Kharchenko ◽  
Sergey Alekseev ◽  
Ilya Zyuzgin ◽  
Anna Artemeva ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
Hematopoietic Stem ◽  
Hodgkin's Lymphomas

Currently there is no single approach to treatment for aggressive diffuse large-cell B-cell lymphoma (Double-HIT and Triple-HIT). Accumulated world data remain controversial and, given the unfavorable prognosis in this subgroup, high-dose chemotherapy with autologous stem cell transplantation in the first line of treatment is a therapeutic option.

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