Safety of Outpatient Stem Cell Mobilization with Low or Intermediate Dose Cyclophosphamide in Newly Diagnosed Multiple Myeloma Patients

Author(s):  
Alessandra Pompa ◽  
Loredana Pettine ◽  
Diana Giannarelli ◽  
Laura Paris ◽  
Lorella Torretta ◽  
...  
Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3321-3321
Author(s):  
Olga Pokrovskaya ◽  
Larisa Mendeleeva ◽  
Irina Kaplanskaya ◽  
Elena Parovichnikova ◽  
Sergei Kulikov ◽  
...  

Abstract BACKGROUND. Angiogenesis is a constant hallmark of multiple myeloma (MM) progression. It has also been reported that bone marrow angiogenesis is a predictive factor of poor survival in newly diagnosed myeloma. The aim of the current study was to investigate the dynamics of bone marrow (BM) microvessel density (MVD) in patients undergoing high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). PATIENTS AND METHODS. 36 patients with newly diagnosed MM (22 in stage II and 14 in stage III according to Salmon and Durie) were included in the study – 21 male and 15 female, median age – 51 ys (range 31–67). All patients underwent HDT that included 3–4 cycles of induction therapy (VAD), stem cell mobilization with cyclophosphamide 6 g/m2 and G-CSF 5 mcg/kg, EDAP and single or tandem ASCT with melphalan 200 mg/ m2. The BM biopsies for histological and immunohistochemical analysis were performed at the time of diagnosis, after induction, after stem cell mobilization before the 1st ASCT and after the end of therapy (5 times during the treatment). The Control group consisted of normal BM donors (7 male and 3 female, median age 29, (17–59)) who underwent BM biopsy during BM harvesting for alloBMT. Blood vessels were highlighted by immunostaining of endothelial cells with a monoclonal antibody to CD34 (Novocastra Lab Ltd). The MVD was calculated in 10 fields using an 40x objective and 16x ocular lens. RESULTS. At diagnosis in all MM pts, MVD was extremely high compared to normal donors (152±8 vs 74±4). A significant decrease of BM MVD was observed after each phase of therapy: after the induction therapy the MVD was 124±6; before the 1st ASCT – 109±5 and at the end of treatment – 97±3. There was a statistically significant increase of MVD after stem cell mobilization due to G-CSF (143±4). Although there was a marked decrease of BM MVD in MM pts with CR or VGPR, it nevertheless stayed significantly higher compared with control group (p<0,001). The analysis of probability of CR or VGPR duration after ASCT according to MVD at different phases of therapy showed that MVD at diagnosis and before the 1-st ASCT are important prognostic factors. Probability of duration of CR or VGPR was 63% in group with low MVD before the 1st ASCT compared with 15% in group with high MVD (p<0,02). MVD was revealed to be more powerful prognostic factor for progression free survival (PFS) then CR or VGPR achievement. CONCLUSION. BM angiogenesis is increased in patients with MM. BM MVD is decreased during and after treatment however even after the completion of HDT and ASCT, the MVD is higher then in the normal control group. There is a statistically significant increase of MVD after stem cell mobilization with cyclophosphamide and G-CSF. MVD at the time of diagnosis and before the 1-st ASCT are important prognostic factors for overall-survival and PFS after ASCT. MVD before the 1-st ASCT appears to be a more powerful prognostic factor for PFS then remission rate.


2020 ◽  
Vol 105 (1) ◽  
pp. 30-34 ◽  
Author(s):  
Efrat Luttwak ◽  
Odelia Amit ◽  
Irit Avivi ◽  
Svetlana Trestman ◽  
Rinat Eshel ◽  
...  

Leukemia ◽  
2011 ◽  
Vol 25 (10) ◽  
pp. 1627-1631 ◽  
Author(s):  
F Cavallo ◽  
S Bringhen ◽  
G Milone ◽  
D Ben-Yehuda ◽  
A Nagler ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5900-5900
Author(s):  
Wolfram Poenisch ◽  
Madlen Ploetze ◽  
Bruno Holzvogt ◽  
Marc Andrea ◽  
Thomas Zehrfeld ◽  
...  

Abstract Introduction: Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205-212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing. Material and Methods: A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with multiple myeloma who had received at least two cycles of a BPV induction therapy consisting of bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m² on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m2 and G-CSF (2x5µg/kg). Apheresis was started as soon as peripheral blood CD34+ counts exceeded 20x106/l with a harvest target of 8x106 CD34+/kg. The minimal accepted target was 2x106 CD34+/kg. Results: A median number of two (range 1–5) BPV treatment cycles were given to the patients. The majority of the patients (n = 31, 89 %) responded including 2 sCR, 5 nCR, 11 VGPR, and 13 PR. Three patients had MR, and 1 SD. Stem cell mobilization and harvest was successful in all patients. In 19 of 35 patients (54 %) a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1-4) and the median CD34+ cell-count/kg was 13.5 (range 3.2-33.1) x106. All patients received an autologous SCT. The pre-transplantation conditioning therapy consisted of melphalan 200 mg/m2. In 8 patients with concomitant heart amyloidosis or severe renal insufficiency melphalan dose was reduced to 100 or 140 mg/m2. Engraftment was successful in 34 of 35 patients. The median time to leucocytes count >l×109/l was reached after 11 (range 9–18) days and the time to untransfused platelet count of >50×109/l was 13 (range 10–55) days. 34 patients (97%) responded after the autologous SCT with 11 sCR, 2 CR, 7 nCR, 7 VGPR, and 7 PR. The progression free survival at 18 months was 87 % and overall survival was 92 %. Conclusion: Stem cell mobilization and autologous SCT is feasible in multiple myeloma patients who have received BPV induction therapy. Disclosures Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Lange:Novartis: Consultancy, Honoraria, Research Funding.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2931-2931
Author(s):  
Devendra K. Hiwase ◽  
Anthony P. Schwarer ◽  
Joe J. Mckendrick ◽  
Geraldine M. Bollard ◽  
Smita D. Hiwase ◽  
...  

Abstract Aim: Autologous peripheral blood stem cell transplant (PBSCT) is standard of care for multiple myeloma patients younger than 65 years of age. However there is no agreement on mobilization regimen for PBSC collection. We have compared efficacy and toxicity of low dose & intermediate dose of cyclophosphamide for stem cell mobilization. Methods: Eighty-seven patients with multiple myeloma had stem cell mobilization: Intermediate dose cyclophosphamide (3 to 4 gm/m2) [ID-CY] was used between Jan 1995 to Jun 2002 and low dose cyclophosphamide (1 to 2 gm/m2)[LD-CY] was used between 2002 and 2004. Mobilization chemotherapy: LD-CY or ID-CY was infused along with hydration, antiemetics and mesna. Stem cell collection was planned between day 10 to day 14 after chemotherapy and G-CSF 10 ug/kg (5 to 20 ug/kg) was started 4 days prior to stem cell collection. PBSC collected by processing 7 litres of blood by Fenwal CS3000 (Baxter) or Cobe Spectra. Statistical Analysis: The Mann-Whitney U and Kruskal-Waliis test were used for comparison between treatment groups. Chi-Square and Fisher exact test were used for comparisons of categorical variables Result: There were 87 patients of multiple myeloma, 61 in LD-CY group and 26 in ID-CY group. There was no statistically significant difference between two groups for basic demographic, disease parameters & prior duration of treatment. The median G-CSF/kg dose was similar in both groups. Comparison of Stem cell collection and toxicity: LD-CY Vs ID-CY CD34 Yield LD-CY ID-CY P Number of Patients 61 26 Total CD34/kg Median (Range) 5.17 (0.23 to 17.3) 7.71 (0.08 to 26.4) 0.018 Total CD34/kg/L Median (Range) 0.62 (0 to 2.47) 1.07 (0.01 to 3.77) 0.010 CD34/kg on 1st day of leukapheresis 2.33 (0.03 to 15.8) 5.11 (0.04 to 15.9) 0.001 number of patients collected &gt; 2 x 10^6/kg 54/61 (88%) 24/26(92%) Number of Leukapheresis Median (Range) 2 (1 to 5) 2 (1 to 3) 0.001 Number of patients had febrile neutropenia 8/61(13%) 10/26 (38%) 0.0085 Number of patients required antibiotics 8/61 (13%) 10/26(38%) 0.0085 Number of patients requiring hospitalisation 10/61(16.39%) 11/26 (42.30%) 0.010 Conclusion: There was statistically significant higher stem cell yield with ID-CY as compared to LD-CY, however at the cost of increased toxicity. In LD-CY group 88% patients had &gt;2 x106/kg stem cells collected which is sufficient for single autograft. We conclude that LD-CY mobilisation chemotherapy is adequate for patients who are planned for single autograft with minimal toxicity.


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