Evaluation of MRD Status by Flow Cytometry and PCR in Multiple Myeloma Elderly Patients Receiving Autologous Stem Cell Transplantation After Bortezomib-Supplemented Mobilization and Conditioning

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4523-4523
Author(s):  
Immacolata Attolico ◽  
Roberta Nuccorini ◽  
Alberto Fragasso ◽  
Vincenzo Pavone ◽  
Pellegrino Musto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Residual Disease ◽  
Patient Specific ◽  
High Dose

Abstract Abstract 4523 Autologous Stem Cell Transplantation (ASCT) is still an option for eligible patients with Multiple Myeloma (MM). High-dose melphalan (HDM: 200mg/m∧2) is the recommended conditioning before ASCT, but synergistic effects of Bortezomib (BOR) and HDM have been reported in vitro and in vivo. PATIENTS AND METHODS: We evaluated in 56 MM fit elderly patients (median age 65 yrs), the feasibility and efficacy (also in terms of evaluation of minimal residual disease: MRD) of a strategy, combining BOR, Cyclophosfamide (CY) and dexamethasone (DEX) as induction and mobilizing therapy (CY-BOR), for ASCT, with conditioning including BOR-HD-MEL. The patients achieving at least PR after 4 CY-BOR courses, were mobilized with BOR and DEX standard schedule with CY 3g/m∧2 (day 8). The pts collecting at least 2.5×10∧6CD34+/kg underwent ASCT with HD-MEL (day-1) and BOR (1.0mg/m∧2 on -6,-3,+1,+4), followed by thalidomide consolidation until Relapse/Progression. The MRD has been prospectively evaluated both by using 4 colour flow cytometry (FC), and by using patient-specific probes, by ASO-PCR. The percentage of plasma cells (PCs) has been evaluated both in in PBSC harvested and in bone marrow, with CD38, CD45, CD56, CD138, CD19, CD27, CD28, CD117, kappa and lambda, along different steps of therapy. RESULTS: Of 44 pts evaluable for response before ASCT, 32 (73%) achieved 3PR and 30 (68%) were mobilized: 29 (66%) collected3 2.5×106CD34+/kg and 25 underwent ASCT. Median time for PMN engraftment was 11 days (range 10–13) and 14 (range12–20) for PLT>=20.000/mcl. We observed grade 3 neuropathy in 3 patients and pneumonia during induction in 2 patients. At day +180 from ASCT 23 are evaluable for response and 21 for MRD: 3 pts have progressive disease (PD), 2 pts have a PR, 4 pts have a VGPR, 10 pts a nCR and 4 pts a CR. Four colour FC, in order to detect clonal plasmacells (cPCs) along several steps of treatment, showed that 3 pts (14%) achieved MRD negativity: 1/21 pts achieved MRD negativity at day +180 (cPC <0.01%), being positive after induction and at day +90 after ASCT; two patients were MRD negative after induction (one developed positivity at day + 180 and relapsed at day +365 from ASCT; the other one became positive at day +90 after ASCT and, is in CR at 10 months from ASCT). In 5 patients we evaluated MRD by PCR with patient-specific probes. One patient achieved clearance of MRD after induction and still maintains negative of PCR at 27 months from ASCT: this patient had positivity of MRD by flow cytometry after induction and at 90 months from ASCT, then became negative and is in CR. One became PCR negative after ASCT: flow cytometry was negative too and the patient is in CR at 10 months from ASCT; the remaining three patients are PCR positive: two of them experienced progression of disease. CONCLUSIONS: ASCT with HDM and BOR is feasible in older patients, with very high RRs and without major toxicities. We need a longer follow up and a larger number of pts to assess if these results will translate in a benefit in terms of outcome. Disclosures: Fragasso: Mundipharma: Honoraria.

Immunotherapy with Rituximab after Peripheral Blood Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5232-5232
Author(s):  
Celso Mitsushi Massumoto ◽  
Edilson Pinheiro Junior ◽  
Otávio C.G. Baiocchi ◽  
Ronald Pinheiro ◽  
Adelson Alves
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Clinical Characteristics ◽  
Residual Disease ◽  
High Dose

Abstract Introduction: autologous stem cell transplantation is a potentially curative or may augment the time to progression in Multiple Myeloma (MM) patients. The immunotherapy with rituximab may help control the minimal residual disease after high dose chemotherapy. Twenty percent (20%) of Multiple Myeloma patients express the CD20+ protein and can be target for immunotherapy. Objective: The aim of this study was to evaluate the use of rituximab after autologous stem cell transplantation for Multiple Myeloma. Patients and Methods: eight patients (4 male) with a median age of 53 (range 43–59) years diagnosed with MM. All of them had received at least one previous regimen were enrolled in the protocol study. All patients signed the consent form. Patients in relapse received a salvage regimen with C-VAD n=2 (cyclofosfamide 4 g/m2 e vincristine 0.4 mg/d (d 1–4), doxorrubicin 0.9 mg/m2 (d1-4) e dexametasone 40 mg (d1-4; 9-12; 17–22) or cyclofosfamide (1OO mg/kg, n=7) followed by stem cell harvesting. The preparative regimen was Busulfan 12 mg/kg and cyclofosfamide 120 mg/kg or Melphalan 200mg/m2. Rituximab at a dose of 375mg/m2 weekly x 4 was given every 6 months for 2 years after SCT. The clinical characteristics of the patients are shown on Table 1. Results: the median time to ANC and platelets engraftment was 11 (range 8–12) and 26 (range 17–35) days. Patients have been in CR at a median time of 11 months follow-up. Minor Rituximab-associated toxicities were seen:rigor, fever and short of breath that were controlled with acetaminophen and diphenidramine. Conclusion: the Rituximab given after autologous stem cell transplantation is safe in Multiple Myeloma patients and may prolong time to disease progression. A randomized study is required to evaluate the role of rituximab after ASCT. Table 1 - Clinical Characteristics of Patients Patients Age/gender Status Pre- BMT Status Post- BMT Salvage Tx Prep. regimen ANC/Platelets X1000 MM3/ml Follow-up (months) FRC 57/M PR PR C-VAD BU+MEL 12/28 EXPIRED MB 52/F CR1 CR1 C-VAD BU+MEL 12/60 EXPIRED AM 52/F PR PR C-VAD BU+MEL 9/26 EXPIRED IM 54/M PR CR Cyx2 BU+MEL 12/21 ALIVE GAD 50/F PR CR Cyx2 BU+MEL 12/35 ALIVE SCM 59/M CR CR Cyx2 BU+MEL 10/17 ALIVE MAD 63/F CR CR C-VAD MELPHALAN 12/25 ALIVE JFC 51/M CR CR C-VAD BU+MEL 12/18 ALIVE

Prognostic Impact of Chromosomal Abnormalities in Elderly Patients with Multiple Myeloma Treated with High-Dose Melphalan (MEL140) and Autologous Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 992-992
Author(s):  
Peter Liebisch ◽  
Christian Straka ◽  
Astrid Wimmer ◽  
Christiane Wendl ◽  
Axel Hinke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Chromosomal Aberrations ◽  
Chromosomal Abnormalities ◽  
Chromosome Band ◽  
High Dose

Abstract Background: Although chromosomal aberrations (CA) have emerged as important outcome predictors in multiple myeloma (MM), the prognostic significance of many recurring genomic changes is still unknown. Moreover, there is only scarce data on the implication of chromosomal abnormalities in elderly patients (pts.) receiving high-dose chemotherapy (HD-CTX) followed by autologous stem cell transplantation (ASCT). Aims: To evaluate the prognostic relevance of recurring chromosomal aberrations as detected by cIg-FISH for elderly pts. with MM receiving HD-CTX and ASCT. Materials: Between 05/2001 and 08/2006, 549 pts. 60–70 yrs. of age with newly diagnosed symptomatic MM entered the DSMM II trial of the Deutsche Studiengruppe Multiples Myelom to receive two cycles of HD-CTX (melphalan 140 mg/sqm) followed by ASCT after 3–4 cycles of dexamethason-based induction chemotherapy (IC; arm A1) or no IC (arm A2). cIg-FISH and DNA probes mapping to chromosome bands 1q21.2, 9q34, 11q25, 13q14, 14q32, 17p13, and 22q11 were applied to all pts. from whom sufficient bone marrow specimen were obtained. 152 pts. with a median age of 65 yrs. for that information on all genomic loci was available were included in the present analysis. The clinical database was last updated in 04/2007. Results: The median follow-up of time in the present series was 83 (1–264) weeks. Univariate analysis showed significantly shorter EFS in 14 out of 152 pts. (9%) with chromosome 17p13 deletion (17p−; 46 vs. 99 weeks, p<0.0001) and 18 out of 152 pts. (12%) with translocation t(4;14) (57 vs. 99 weeks, p=0.001). Clinical and laboratory variables as well as all other CA had no significant impact on EFS. Multivariate analysis revealed 17p− and t(4;14) as independent predictors of inferior EFS (p=0.0005 and p=0.01, respectively). OS was significantly shorter in pts. with 17p− (99 vs. 219 weeks, p=0.001) and in 17 out of 152 pts. (11%) with deletion of chromosome band 22q11 (127 weeks vs. not reached, p=0.002). There was a trend towards a shorter OS in pts. with t(4;14). Conclusions: Our data suggest that HD-CTX and ASCT does not provide long-term disease control in elderly pts. with t(4;14) or 17p−. Therefore, HD-CTX and ASCT cannot be recommended for these high-risk pts. (overall ∼20% of cases). 13q− and +1q21.2 were not prognostic markers in the present study. Collection of clinical data and molecular cytogenetic analysis of further cases is ongoing.

Prognostic Impact of Chromosomal Abnormalities In Elderly Patients with Multiple Myeloma Treated with High-Dose Melphalan (MEL140) and Autologous Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1914-1914
Author(s):  
Peter Liebisch ◽  
Christian Straka ◽  
Hermann Einsele ◽  
Axel Hinke ◽  
Andreas Sandermann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Significance ◽  
High Dose ◽  
Prognostic Impact ◽  
Newly Diagnosed

Abstract Abstract 1914 Background: Although chromosomal aberrations (CA) have emerged as important outcome predictors in multiple myeloma (MM), the prognostic significance of many recurring genomic changes is still unknown. Moreover, there is only scarce data on the implication of CA in elderly patients (pts.) receiving high-dose chemotherapy (HD-CTX) followed by autologous stem cell transplantation (ASCT). Aims: To evaluate the prognostic relevance of recurring CA as detected by cIg-FISH for elderly pts. with MM receiving HD-CTX and ASCT. Patients and Methods: Between 05/2001 and 08/2006, 549 pts. 60–70 yrs. of age with newly diagnosed symptomatic MM entered the DSMM II trial of the Deutsche Studiengruppe Multiples Myelom to receive two cycles of HD-CTX (melphalan 140 mg/sqm) followed by ASCT after 3–4 cycles of dexamethason-based induction chemotherapy (IC; arm A1) or no IC (arm A2). cIg-FISH and DNA probes mapping to chromosome bands 1p22, 1q21.2, 6q21, 8p11.2, 9q34, 11q25, 13q14, 14q32, 17p13, and 22q11 were applied to all pts. with sufficient bone marrow specimen at diagnosis. 289 pts. with a median age of 64 yrs. were included in the present analysis. Results: After a median follow-up of 82 weeks (w) the following CA were associated with a significantly shorter event-free survival (EFS): 17p13 deletion (17p–; 55 vs. 93 w, p<.0001); translocation t(4;14) (t(4;14); 65 vs. 95 w, p<.001), 1q21.2 gains (+1q21.2; 79 vs. 99 w, p=.0002); 13q14 deletion (13q–; 82 vs. 99 w, p=.03); and 8p11.2 deletion (8p–; 80 vs. 95 w, p=.04). Overall survival (OS) was significantly shorter in pts. with +1q21.2 (148 vs. 231 w, p<.0001); 17p– (118 vs. 219 w, p=.001); and t(4;14) (t(4;14); 195 vs. 223 w, p=.017). In a multivariable analysis t(4;14) (p<.001); 17p– (p=.0089); +1q21.2 (p=.031); and beta-2-microglobulin (p=.033) independently predicted outcome. Conclusion: In this large cohort of uniformly treated elderly pts. with newly diagnosed MM, CA – in particular 17p–, t(4;14), and +1q21.2 – remain strong predictive markers for outcome. Supported by a grant from the Else Kröner-Fresenius-Stiftung to P.L. and H.D. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document