scholarly journals A Phase I/II Study of Escalating Doses of Bortezomib in Conjunction with High-Dose Melphalan as a Conditioning Regimen for Salvage Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma

2016 ◽  
Vol 22 (12) ◽  
pp. 2165-2171 ◽  
Author(s):  
Noa Biran ◽  
Scott D. Rowley ◽  
David H. Vesole ◽  
Shijia Zhang ◽  
Michele L. Donato ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Conditioning Regimen ◽  
High Dose ◽  
High Dose Melphalan ◽  
Blood Stem Cell Transplantation

Incidence of Clostridium Difficile-Induced Diarrhea in Patients Treated with High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma and Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5059-5059
Author(s):  
Jorge I. Arango ◽  
Cesar O. Freytes ◽  
Deanna L. Schneider ◽  
Alejandro Restrepo ◽  
Marcos I. Restrepo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Blood Stem Cell Transplantation

Abstract Introduction: Diarrhea is a major cause of morbidity and discomfort for patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). There are multiple causes of diarrhea in patients undergoing APBSCT including chemotherapy, medications, and infection. The incidence of C. difficile-associated diarrhea (CDAD) in patients undergoing APBSCT has been reported to be in the range of 5 to 7%. A preliminary analysis from our group showed that patients with multiple myeloma had a higher incidence of CDAD than previously reported (Restrepo et al, Biol Blood Marrow Transplant 2002, 8:104). Purpose: To compare the incidence of CDAD in subjects treated with high-dose chemotherapy and APBSCT for multiple myeloma and lymphoma, and to identify risk factors for the development of CDAD. Methods: Retrospective analysis of 244 medical records of patients who underwent APBSCT for multiple myeloma and lymphoma from October 1996 until October 2001 at our institution. CDAD was defined as diarrhea with detectable C. difficile toxin A in stool. Patient-, disease- and transplant-related parameters analyzed included age, sex, race, performance status, diagnosis, agents utilized for PBSC mobilization, conditioning regimen, amount of CD34-positive cells infused, use of growth factors, presence and duration of fever, presence and duration of neutropenia, antimicrobial therapy and the frequency of testing for the presence of C. difficile toxin in stool were analyzed. Results: Diarrhea was reported in 157 subjects. One hundred and thirty-five subjects were tested for the presence of C. difficile toxin A and comprise the study group. The incidence of CDAD in this cohort was 15% (21 patients). Of the 21 patients, 14 (67%) had multiple myeloma and 7 (33%) had lymphoma. The use of cephalosporins (P=0.011), use of intravenous vancomycin (P=0.021), and the use of cyclophosphamide as part of the mobilization regimen (P=0.013) were the only risk factors associated with the development of CDAD. Conclusion: The incidence of CDAD at our institution was twice that previously reported. Antibiotic therapy with cephalosporins and intravenous vancomycin was associated with the development of CDAD, as well as the use of cyclophosphamide as part of the mobilization regimen. Although the incidence of CDAD in patients with multiple myeloma was higher than in patients with lymphoma, this difference did not attain statistical significance. Patients tested for C. diff Patients with positive tests P values Sex: NS     Male 123 (91.1%) 20 (95.2%) Age: NS     Mean (Range) 55 (22 to 78) 56 (22 to 78) Diagnosis: NS     Myeloma 72 (53.3%) 14 (66.7%)     Lymphoma 63 (46.7%) 7 (33.3%) Mobilization regimen: 0.013     GF 51 (37.7%) 9 (42.8%)     GF+Cy 46 (34.1%) 9 (42.8%)     GF+Tx 34 (25.2%) 1 (4.8%)     Other 3 (2.2%) 2 (9.6%)     NK 1 (0.8%) 0 (0%) Conditioning regimen: NS     CVB 54 (40%) 7 (33.3%)     Melphalan 50 (37%) 11 (52.4%)     Bu/Mel 9 (6.7%) 1 (4.8%)     Bu/Cy 9 (6.7%) 1 (4.8%)     Other 13 (9.6%) 1 (4.8%) Antimicrobials Penicillins 20 (14.8%) 2 (9.5%) NS Cephalosporins 28 (20.7%) 9 (42.9%) 0.011 Vancomycin 36 (26.7%) 10 (47.6%) 0.021 Aminoglycosides 23 (17.0%) 5 (23.8%) NS Macrolides 7(5.2%) 0 (0.0%) NS Amphotericin B 6 (4.4%) 0 (0.0%) NS Other AB 1 (0.7%) 0 (0.0%) NS

Results of a Phase II Open-Label Trial of Bortezomib in Patients with Multiple Myeloma Who Have Undergone High-Dose Melphalan Therapy Followed by Autologous Peripheral Blood Stem Cell Transplantation and Failed to Achieve a Complete Response

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2780-2780
Author(s):  
Robert M. Rifkin ◽  
Gary Spitzer ◽  
Andrew Greenspan ◽  
John F. Schwerkoske ◽  
Romeo A. Mandanas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Complete Response ◽  
High Dose ◽  
New Treatment ◽  
High Dose Melphalan ◽  
Blood Stem Cell Transplantation

Abstract Multiple myeloma (MM) is the second most common hematologic malignancy. Presently, the majority of suitable MM patients who undergo high-dose melphalan therapy followed by autologous peripheral blood stem cell transplantation (PBSCT) fail to achieve a complete response (CR). This suggests that treatment options following autologous transplantation are needed. Moreover, there is a need to determine the optimal role of maintenance therapy following PBSCT in MM. Over time, Bortezomib (B) has been shown to be an active agent in the treatment of newly diagnosed, and relapsed or refractory MM. Therefore, the primary objective of this study was to determine the efficacy of B treatment after high-dose melphalan therapy followed by PBSCT in MM. Fifty patients (pts) were enrolled between March 2004 and November 2007, and 47 were evaluable (2 pts ineligible and 1 pt data pending). Pts received B 1.3 mg/m2 IV on Days 1, 4, 8, and 11 of each 21-day cycle. Pts were treated for 4 cycles or until evidence of disease progression or intolerable toxicity. If an improvement in response was noted after Cycle 4, pts could receive up to 4 additional cycles. To reduce the incidence of varicella zoster infection, antiviral prophylaxis (acyclovir 400 mg PO BID) was taken for the duration of the study. The median patient age was 56 years (range, 39–74), 82% were white, and 68% were male. The majority of pts (64%) had ECOG PS 0, 44% were Durie-Salmon Stage IIIA prior to induction therapy. Forty percent had symptomatic IgG-kappa multiple myeloma. Of all pts, 74% had a single transplant, while 24% had tandem transplants (2% [n=1 pt] data pending). Sixty-eight percent of pts had a PR and 18% had a MR following their transplant(s). While on study, pts received a median of 4 cycles (range, 2–8) of therapy with B. Efficacy results for the evaluable population are: CR 4%, unconfirmed (u) CR 4%, PR 21%, uPR 17%, MR 11%, and No Change 36%. Median time-to-treatment failure was 5.8 months (mos) (range, 0.2–19.4). There were 2 on-study deaths (sepsis and PD). Grade 3–4 treatment-related toxicities reported in >1 pt were thrombocytopenia (15%), asthenia (10%), neutropenia or neuropathy (8% each), peripheral neuritis (6%), and nausea (4%). Twenty patients discontinued study treatment due to toxicity (22%), pt request (6%), disease progression, ineligibility, and intercurrent illness/protocol deviation (4% each). 26 pts (52%) completed the study; 4 pts are still on study (8%). Sixteen pts started new treatment; median time from start of study treatment to the start of new treatment was 5.2 mos (range, 1.5–17.6 mos). The study was closed earlier than the planned due to the widespread availability of B, and the inability to find B-naïve patients. Bortezomib given after high-dose melphalan therapy and autologous PBSCT was well-tolerated with manageable adverse events. Updated cytogenetic analysis will be available for presentation.

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