scholarly journals Residual malignant and normal plasma cells shortly after high dose melphalan and stem cell transplantation. Highlight of a putative therapeutic window in Multiple Myeloma?

Oncotarget ◽  
2012 ◽  
Vol 3 (11) ◽  
pp. 1335-1347 ◽  
Author(s):  
Anouk Caraux ◽  
Laure Vincent ◽  
Salahedine Bouhya ◽  
Philippe Quittet ◽  
Jérôme Moreaux ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cells ◽  
Therapeutic Window ◽  
High Dose ◽  
Normal Plasma ◽  
High Dose Melphalan

The Reason Why High-Dose Melphalan Followed by Autologous Stem-Cell Transplantation Produces Good Response in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5201-5201
Author(s):  
Yoshiaki Kuroda ◽  
Akira Sakai ◽  
Yoshiko Okikawa ◽  
Shoso Munemasa ◽  
Yuta Katayama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Plasma Cells ◽  
High Dose ◽  
Myeloma Cells ◽  
Before And After ◽  
High Dose Melphalan

Abstract Multiple myeloma (MM) is the result of a clonal proliferation of plasma cells. And myeloma cells have been shown to be heterogeneous with regard to their morphology and biological character. Recently, correlations between molecular subtypes and prognosis have been identified as a good prognosis with t(11;14) and a poor prognosis with t(4;14) and t(14;16) besides chromosome 13 abnormalities. But it is still unclear how those molecular events work on the prognosis of MM patients. And it is difficult to find the heterogenesity of myeloma cells in each MM case by molecular analysis. Twenty years ago Greipp et al. classified myeloma cells as mature, intermediate, immature and plasmablastic type, and then they showed that plasmablastic morphology is an independent predictor of poor survival rate after autologous stem-cell transplantation. On the other hand, Kawano et al. classified myeloma cells into three types by their phenotype (Huang N, Blood82: 3721, 1993, Kawano MM, Blood82: 564, 1993); immature (MPC1−, CD49e−, CD45−/+), intermediate (MPC1+, CD49e−, CD45−), and mature (MPC1+, CD49e+/−, CD45+). This classification according to the phenotype is good correlation with that by morphology. And they indicated that immature myeloma cells have activity of proliferation. We analyzed both phenotypic and morphological findings of myeloma (plasma) cells consecutively before and after chemotherapy in 23 MM cases in order to find what kind of drug might be useful to reduce the main population of heterogeneous myeloma cells. The phenotypic and morphological analysis were performed before and after ten-cycles of melphalan-predonine (MP) in 2 cases, three or four-cycles of vincristine-doxorubicin-dexamethasone (VAD) in 10 cases, high-dose cyclophosphamide (HD-CPA) for stem cell harvest after three or four cycles of VAD in 5 cases, high-dose melphalan followed by autologus stem-cell transplantation (HD-Mel+ASCT) in 6 cases, and administration of thalidomide at least for two months in 7 cases. First, total myeloma cells decreased after VAD, however, immature myeloma cells increased relatively (9/10). Second, HD-CPA was not effective in reducing myeloma cells furthermore after VAD (5/5). Third, HD-Mel+ ASCT could reduce immature myeloma cells clearly (4/6). In particular, a less than 5% reduction of immature myeloma cells after this course were important for the long duration of good response, but the residue of immature myeloma cells was a predictor of progressive disease (PD). Interestingly, MP was also useful to reduce immature myeloma cells (2/2). Finally, thalidomide was effective in reducing mature and intermediate myeloma cells (3/6), but not effective in immature myeloma cells. In conclusion, melphalan, if it is high-dose, has more effects on immature myeloma cells compared with those of other drugs, which might be a reason of the superiority of HD-Mel+ASCT over conventional treatment in terms of the response rate and event-free survival.

Comparison of conditioning regimen toxicities among autologous stem cell transplantation eligible multiple myeloma patients: High-dose melphalan versus high-dose melphalan and bortezomib

2017 ◽  
Vol 24 (4) ◽  
pp. 281-289 ◽  
Author(s):  
Eda Aypar ◽  
Fikret Vehbi İzzettin ◽  
Şahika Zeynep Akı ◽  
Mesut Sancar ◽  
Zeynep Arzu Yeğin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Standard Of Care ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Duration Of Hospitalization ◽  
High Dose Melphalan

Background Autologous hematopoietic stem cell transplantation (AHSCT) remains the standard of care for younger patients with multiple myeloma (MM). Currently, high-dose melphalan (HDM) is recommended as conditioning regimen before AHSCT. Preclinical data suggest that combining bortezomib and melphalan has synergistic effect against multiple myeloma cells. Bortezomib and HDM (Bor-HDM) combination as conditioning regimen has been investigated by many other investigators. Objective In this retrospective study, we aimed to compare transplant-related toxicities and hematologic recovery of HDM and Bor-HDM conditioning regimens. Method We retrospectively evaluated hematologic recovery and toxicity profile in patients with MM who received AHSCT with either HDM ( n = 114) or Bor-HDM ( n = 53) conditioning regimen. Results Nonhematologic toxicities were comparable between HDM and Bor-HDM conditioning regimen, except mucositis and diarrhea being more frequent in the Bor-HDM group. Neutrophil and platelet engraftment time and duration of hospital stay were significantly shorter for HDM regimen. Conclusions In this retrospective analysis, we observed engraftment kinetics and duration of hospitalization were significantly worse in Bor-HDM conditioning regimen with manageable toxicities. Randomized studies are needed to further compare Bor- HDM regimen to HDM in terms of response rates, toxicities, and transplant-related mortality.

High-dose melphalan on day 2 versus 1 before autologous stem cell transplantation for multiple myeloma.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 6545-6545
Author(s):  
K. Rakszawski ◽  
J. J. Drabick ◽  
N. G. Dolloff ◽  
J. M. Sivik ◽  
J. Malysz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
High Dose ◽  
High Dose Melphalan
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