Bortezomib washout duration prior to stem cell mobilization in patients with newly diagnosed multiple myeloma

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


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.


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