Autografting Followed Closely by Nonmyeloablative Allografting as Consolidation Immunotherapy Reduces Disease Progression Compared to Tandem Autografting in Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1126-1126
Author(s):  
A.M. Carella ◽  
M. Spriano ◽  
M. T. Corsetti ◽  
P. Scalzulli ◽  
G. Beltrami ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Disease Progression ◽  
Remission Rate ◽  
Conditioning Regimen ◽  
Clinical Signs ◽  
Disease Free Survival ◽  
Disease Status ◽  
High Dose ◽  
Immunological Responses

Abstract Autografting (AutoSCT) has been limited by high-relapse rates and conventional allografting (AlloSCT) by excessive TRM and toxicity in the treatment of Multiple Myeloma (MM). Reduced intensity conditioning for transplant (RICT), a less toxic procedure for AlloSCT that aims to exploit graft versus tumor effect, has been shown to achieve remissions in MM. High-dose therapy/AutoSCT followed shortly thereafter by RICT might improve outcomes in MM as compared to AutoSCT or conventional AlloSCT used alone. We compared two retrospective cohort of patients who underwent either tandem AutoSCT (HDT consisted of Melphalan 200 mg/m2) or AutoSCT followed closely by related RICT (patients with HLA-matched siblings). The two groups were matched for pre-transplant therapy, disease status at transplant, time from diagnosis to transplant. GVHD prophylaxis for RICT patients consisted of CyA/MTX. The major results are summarized in the Table. In the AutoSCT/RICT group the complete remission rate was higher (p=0.004) and the risk of disease progression after transplant was significantly reduced (p=0.005). All patients who reached CR responded after full chimerism and GVHD developed. This finding confirms the existence of a graft-versus-myeloma effect. Since the first clinical signs of response in remitters patients were noted between 70 and 120 days and maximum response between 160 and 200 days after RICT (after DLI in one patient), these responses should be considered immunological responses. These data suggest than an allograft following an AutoSCT significantly reduces the incidence of disease progression. Tandem ASCT (N=35) ASCT + RICT (n=20) Age, median 56 (range, 38–66) 51 (range, 34–63) Median prior cycles of Chemoth. 4 (range, 3–6) 4 (range, 3–6) Time from Dx to 1st AutoSCT (median mo.) 6 (range, 5–60) 9 (range, 7–42) Conditioning Regimen for AutoSCT Melphalan (200 mg/m2) Melphalan (200 mg/m2) Conditioning Regimen for RICT --- TBI/Fludarabine Complete Remission 14% 50% p=0.004) Disease-Free Survival at 3 yrs 11% 45% (p=0.005) Overall Survival at 3 yrs 66% 70% (p=NS) Median Follow-Up (mo.) 30 (range, 6–104) 38 (range, 5–59) Transplant-Related Mortality 0% 0% Median days from AutoSCT to RICT --- 80

Reduced Intensity Conditioning Regimen for Allografting Following Autografting Has Strong Anti-Myeloma Activity and Delays Disease Progression Compared to Tandem Autografting.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 51-51
Author(s):  
A.M. Carella ◽  
E. Lerma ◽  
S. Nati ◽  
A. Congiu ◽  
E. Rossi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Disease Progression ◽  
Remission Rate ◽  
Conditioning Regimen ◽  
Complete Remission Rate ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
High Dose Therapy ◽  
Reduced Intensity

Abstract Multiple Myeloma (MM) is still an incurable disorder despite the numerous attempts to exploit new therapy approaches for it. The better understanding of its molecular pathogenesis has led to the development of effective, novel therapeutic agents like thalidomide and the proteasome inhibitor bortezomib. High-dose therapy with stem cell transplantation and novel targeted therapies represent two approaches to overcome resistance of multiple myeloma cells to conventional treatments. Autografting (AutoSCT) has been limited by high-relapse rates and conventional allografting (AlloSCT) by excessive TRM and toxicity. Reduced intensity conditioning for transplant (RICT), a less toxic procedure for AlloSCT that aims to exploit graft versus tumor effect, has been shown to achieve remissions in MM. High-dose therapy/AutoSCT followed shortly thereafter by RICT might improve outcomes in MM as compared to AutoSCT or conventional AlloSCT used alone. We compared two retrospective cohort of patients who underwent either tandem AutoSCT (HDT consisted of Melphalan 200 mg/m2) or AutoSCT followed closely by related RICT (patients with HLA-matched siblings). The two groups were matched for pre-transplant therapy, disease status at transplant, time from diagnosis to transplant. GVHD prophylaxis for RICT patients consisted of CyA/MTX. The major results are summarized in the Table. In the AutoSCT/RICT group the complete remission rate was higher (p=0.004) and the risk of disease progression after transplant was significantly reduced. All patients who reached CR responded after full chimerism and GVHD developed. This finding confirms the existence of a graft-versus-myeloma effect. Since the first clinical signs of response in remitters patients were noted between 70 and 120 days and maximum response between 160 and 200 days after RICT (after DLI in one patient), these responses should be considered immunological responses. Our data demonstrated that RICT following an AutoSCT can mediate a potentially curative graft-versus-myeloma effect and reduces the incidence of disease progression. Tandem ASCT (N=35) ASCT+RICT (n=20) Age, median 56 (range, 38–66) 51 (range, 34–63 Median number of prior cycles of Chemoth. 4 (range, 3–6) 4 (range, 3–6) Time from Dx to 1st AutoSCT (median mo.) 6 (range, 5–60) 9 (range, 7–42) Conditioning Regimen for AutsoSCT Melphalan (200mg/m2) Melphalan (200mg/m2) Conditioning regimen for RICT --- TBI/Fludarabine Median days from AutoSCT to RICT --- 80 Complete Remission rate 14% 50% Disease-free Survival at 4 yrs 14% 45% Overall Survival at 4 yrs 28% 40% Transplant-Related Mortality 0% 0%

Second Autologous or Allogeneic Transplantation after the Failure of First Autograft in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3329-3329
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima Saliba ◽  
Marcos de Lima ◽  
Daniel Couriel ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Albumin Level ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Common Causes

Abstract Background: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually relapse. The optimal salvage treatment for these patients is not very well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage. We analyzed the outcomes of second autologous or allogeneic transplants, performed as salvage in patients relapsing after an autograft. Methods: Fourteen patients received a second autograft for salvage, while thirty-four patients underwent allogeneic transplantation (related 24, unrelated 10). The median age at transplant was 52 years in the autologous group, and 51 years in the allogeneic group. The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The disease characteristics were similar in both autologous and allogeneic groups. Results: With a median follow-up of 10 months among survivors in each group, both autologous and allogeneic transplant groups had a response rate (complete + partial) of 64%. One hundred day nonrelapse mortality was 7% in the autologous group and 12% in the allogeneic group. Median disease-free survival (DFS) was 11 months in the autologous and 6 months in the allogeneic group. Median overall survival (OS) was 29 moths in the autologous and 14 months in the allogeneic group. 1-year DFS was 40% in the autologous group and 22% in the allogeneic group (p = 0.2). 1-year overall survival was 70% in the autologous and 53% in the allogeneic group (p = 0.3). The most common causes of non-relapse mortality were graft vs. host disease (62%) in the allogeneic group, and infections (100%) in the autologous group. On univariate analysis for DFS in allogeneic group, an interval of >1 year between the first and the salvage transplant was the only factor associated with a significantly better outcome (p = 0.01). Disease status at transplant, type of donor, tumor mass, β2 microglobulin level, and serum albumin level did not show any impact on the outcome. Conclusions: Both autografting and allografting are feasible as salvage for myeloma patients relapsing after the first autograft. A slightly better outcome with salvage autografting may be due to decreased toxicity.

scholarly journals The Use of Etoposide, Ara-Cytarabine, and Melphalan (EAM) Conditioning Chemotherapy in Autologous Stem Cell Transplantation (ASCT) for a Patient with Relapsed Hodgkin’s Lymphoma

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Eko A. Pangarsa ◽  
Ridho M. Naibaho ◽  
Vina Yunarvika ◽  
Budi Setiawan ◽  
Damai Santosa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
Remission Rate ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Hodgkin's Lymphoma

Up to 20–40% of patients with Hodgkin’s lymphoma will eventually relapse after treatment, among which early relapse confers a poor outcome. With salvage chemotherapy followed by autologous stem cell transplantation (ASCT), the long-term remission rate is 30%. We report our experience of using a modified-BEAM conditioning regimen without BCNU consisting of etoposide, cytarabine, and melphalan (EAM) in a patient with relapsed Hodgkin’s lymphoma. Before transplantation, the patient achieved second complete remission (CR2) using brentuximab vedotin and ESHAP (BR-ESHAP) chemotherapy. The ASCT went well without significant complications. This case demonstrated the considerable efficacy of EAM protocol as a conditioning regimen in terms of sufficient ablative capabilities, and the patient showed a successful hematopoietic engraftment. Although durability of the disease-free survival needs further observation, it had nearly 18 months of complete remission and the patient was in good performance status at the time of writing this manuscript.

Incorporating Target Immunotherapy into Standard Conditioning Regimen Prior to Autologous Stem Cell Transplantaion (ASCT) Improves the Transplant Outcome for Pateints with Relapsed/Refractroy B Cell Non-Hodgkin Lymphoma (B-NHL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1911-1911
Author(s):  
Mohamed I. Farhat ◽  
Reem Karmali ◽  
Stephanie A. Gregory ◽  
Parameswaran Venugopal ◽  
Mohamad Kassar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Background: Refractory or relapse B-NHL has a poor prognosis with conventional chemotherapy. Autologous stem cell transplant (ASCT) preceded by high dose chemotherapy has been the preferred therapeutic choice for such patients. The majority of the treatment failures occur within one to two years post transplant with disease progression after transplant accounted for most of the failures. The incorporation of targeted immunotherapy (rituximab) into the upfront and relapse setting is becoming of the standard of care for patients with B-NHL. The objective of this study is to evaluate the impact of rituximab (R) on disease free survival (DFS) when added to a standard conditioning regimen -- BEAM (carmustine, cytarabine, etoposide, and melphalan) prior to ASCT. Methods: A single institution retrospective analysis of 53 patients (pts), whom were heavily pre-treated, underwent ASCT between 08/98 & 07/06. All pts received rituximab in combination with high dose cytoxan for stem cell mobilization. 37 pts received R-BEAM and 16 received BEAM prior to ASCT. Actuarial rate for DFS was estimated from the day of SCT using the Kaplan-Meier method. Results: The group was predominantly men, 73% and 78%, with a median age of 57 years for both the R-BEAM and BEAM group. With a median follow up of 15.7 months, 13/37 (32%) and 11/16 (64%) pts who received R-BEAM and BEAM respectively developed disease progression after ASCT. The 2-yr actuarial disease-free survivals (figure1) were 60% and 21% for the R-BEAM and BEAM arm respectively (p=0.006). Conclusion: In this study, the outcome of pts who received R-BEAM compares favorably to those who receive BEAM alone with significant improvement in disease-free survival. Thus, incorporating target immunotherapy into standard conditioning regimen may have altered the natural history of the disease for pts undergoing ASCT for relapsed/refractory B-NHL. Disease Free survival Disease Free survival

scholarly journals The Predictive Significance of Early Metabolic Remission Post Autologous Hematopoietic Transplantation in Lymphomas Conditioned with Either BEAM or a Busulfan-Based Regimen

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1984-1984
Author(s):  
Ioanna Sakellari ◽  
Despina Mallouri ◽  
Varnavas C Constantinou ◽  
Michail Iskas ◽  
Ioannis Batsis ◽  
...  
Keyword(s):  
Complete Remission ◽  
Disease Progression ◽  
Conditioning Regimen ◽  
Post Treatment ◽  
Disease Assessment ◽  
Successful Outcome ◽  
High Dose ◽  
Significant Difference ◽  
Conditioning Regimens

Abstract Fluorine-18-Deoxyglucose Positron Emission Tomography Scan (PET) is a valuable diagnostic tool in many histologic types of lymphomas, with an increasing prognostic role for both pre- and post-treatment disease assessment. In the autologous haematopoietic cell transplantation (AHCT) setting, the prognostic value of pre-AHCT PET has been established by current studies, but the significance of early post-treatment PET negativity has not yet been fully investigated. In this retrospective, single center analysis, we evaluated the role of early post-AHCT (+3 to +6 months) metabolic remission in 98 consecutive lymphoma patients (pts), 60 males and 38 females, with Hodgkin (58, HL) and non-Hodgkin (40, NHL) lymphoma, aged 36 (13-66) years, who underwent high dose chemotherapy followed by autologous stem cell rescue, during the years 2009-2014. The conditioning regimen was either BEAM in 29, or Busulfan-based in 69 pts (Busulfan 9.6mg/kg/d×3d, Etoposide 400mg/m2/d×2d and Melphalan 140mg/m2, BuEM). The pts underwent AHCT for primary refractory (65), or relapsed disease (28) post 3 (1-9) lines of treatment, or as consolidation in first complete remission (5). The pre-AHCT disease status was chemosensitive in 53 pts, including 24 in complete remission (CR) post salvage therapy as evaluated by CTs or/and PET. Seventy seven pts were evaluated by PET at +3 to +6 months while the rest had disease progression by CT assessment after AHCT (7 pts received additional involved field irradiation post-AHCT, as part of the treatment plan). Sixty pts had negative and 17 positive PET in early post-transplant evaluation. The overall response rate at +3 months post-AHCT was 68% (66 of 96 evaluated pts), including 60% (58 pts) in complete remission. With a median follow up of 29 (2 - 76) months (BEAM 18 months, BuEM 45 months), the estimated 5-year disease free survival (DFS) and time to progression (TTP) were similar in both conditioning regimens. Relapse rate was 17% vs 21% in BEAM and BuEM, respectively. At last follow-up 73 (75%) pts were alive and 58 (61%) in CR. Treatment related mortality was low with both regimens (1%). Patients' characteristics according to the conditioning regimen were similar in terms of disease (HL, NHL), disease phase (CR, partial response, stable, progression) and chemosensitivity (x2 test). In HL pts, OS was high and similar in both conditioning groups, with no significant difference in TTP. Similarly, in NHL pts the OS, DFS and TTP were not significantly different in the two groups. In multivariate analysis, disease (HL, NHL), disease phase, chemosensitivity, type of conditioning regimen and early-PET were incorporated. In the whole cohort of pts, favorable factors in terms of OS were HL and early PET-negativity (p=0.02 and p=0.01, respectively), while for TTP chemosensitivity and early PET-negativity (p=0.009 and p=0.006, respectively). In HL pts, early PET-negativity was the only significant factor for superior OS (p=0.02), maintaining a borderline significance with respect to TTP (p=0.06) and disease chemosensitivity (p=0.02). In NHL pts the single significant factor for superior TTP was early PET-negativity (p=0.03). With the limitations of this retrospective analysis, early metabolic complete remission, along with disease chemosensitivity to salvage treatment, seems to be a significant favorable factor in both Hodgkin and NHL pts for improved overall survival and time to disease progression. Additionally, in this study group of pts, both conditioning regimens proved to be similarly efficacious and feasible, remaining the key players for a successful outcome of AHCT in lymphomas. Disclosures No relevant conflicts of interest to declare.

Pretransplatation PET as Major Prognostic Discriminant in IGEV (ifosfamide, gemcitabine, vinorelbine and prednisone) Treated Patients with Relapsed/Refractory Hodgkin's Lymphoma (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3707-3707
Author(s):  
Rita Mazza ◽  
Stefano Luminari ◽  
Massimo Magagnoli ◽  
Michele Spina ◽  
Teodoro Chisesi ◽  
...  
Keyword(s):  
Complete Remission ◽  
Fdg Pet ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Response To Therapy ◽  
High Dose ◽  
Bulky Disease ◽  
The Impact

Abstract Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High-Dose Therapy and Autologous Hematopoietic Progenitor Cells Transplantation for Recurrent or Refractory Hodgkin's Lymphoma: Analysis of King Hussein Cancer Center Results and Prognostic Variables

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Fawzi Abdel-Rahman ◽  
Ayad Hussein ◽  
Mohammad Aljamily ◽  
Abdulhadi Al-Zaben ◽  
Nilly Hussein ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Hodgkin’S Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Disease Status ◽  
Hodgkin's Lymphoma ◽  
Cancer Center ◽  
High Dose ◽  
The Impact

Purpose. to evaluate the outcome of patients with Hodgkin’s lymphoma who underwent autologous transplantation at KHCC bone marrow transplant program. Patients and Methods. Over 6 years, 63 patients with relapsed or refractory Hodgkin’s lymphoma underwent high dose chemotherapy followed by autologous transplant. There were 25.4% patients in complete remission (CR), 71.4% with chemotherapy responsive disease at the time of transplant. Prior to conditioning regimen, 56% received two chemotherapy lines, and, 44% received more than two lines. Results. The main outcomes of the study are the rate of complete remission at day 100, overall survival (OS), relapse-free survival (RFS), The impact of the following variables on OS and RFS: (a) disease status at the time of transplant, (b) number of chemotherapy lines prior to conditioning, (c) age group, (d) time of relapse < or >12 months were investigated. The CR at day 100 was 57%. The median overall survival for the whole group was 40.6 months; the median RFS was 20 months. The only factor which significantly impacts the study outcomes was the number of chemotherapy lines prior to conditioning on OS in favor of patients received two lines. Conclusion. In our study only the number of chemotherapy lines received before conditioning had statistically significant impact on OS.

Serum beta2-Microglobulin before Transplantation Is an Independent Predictor of Outcome in Patients with Multiple Myeloma Treated Using Autologous HCT; a Single Centre Multivariate Analysis in a Series of 81 Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5490-5490
Author(s):  
Beata M. Stella-Holowiecka ◽  
Tomasz Czerw ◽  
Aleksandra M. Holowiecka-Goral ◽  
Sebastian Giebel ◽  
Jerzy Wojnar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Median Time ◽  
Independent Predictor ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Disease Status ◽  
Hazard Ratio ◽  
High Dose ◽  
Increased Risk

Abstract High-dose therapy combined with autologous stem cell transplantation-AHCT has been found effective both for up-front therapy and for management of chemotherapy sensitive relapses in multiple myeloma (MM). The results of five randomized trials are controversial; most have confirmed the advantage of AHCT in terms of CR and DFS but a significantly better OS was reported in only one study. It is unclear whether the entirety of MM patients benefit from the higher efficacy of AHCT versus standard chemotherapy or the better results reflect rather a high efficacy in certain subset of patients. It is of crucial importance therefore to define predictive factors characterizing patients who may benefit from therapy including AHCT. The main objective was to select pre-transplant factors predictive for the efficacy of autoHCT in patient with MM treated using defined standard operating procedures in single center from January 1993 to April 2005. Material and methods: 81 MM patients, undergoing first autoHSCT in single transplant centre: median age at autoHSCT 51 y (31–70), F/M 38/43, median time from diagnosis to autoHSCT 12 months (6–68), MM subtype: IgG n=51, IgA −13, non-secretory-7, not-defined −10; source of stem cells: PB −79, BM -2, conditioning: melphalan 200 mg /m2 (n=76), other (n=5), disease status: CR −30, PR-51. Factors submitted for multivariate analysis: serum beta2-microglobulin (b2-mgl), lactate dehydrogenase (LDH), monoclonal protein level (MoP), bone marrow plasma cell percentage (BM-pc), hemoglobin level (Hb), age ≤60 vs. &gt; 60y and the number of transplanted CD34 positive cells ≤ median value equaling 7,18 x 106/kg vs. &gt; this number. Factors were measured within the median time of 7 d before initiation of conditioning regimen. Results: The transplant related mortality at day 100 was 3,7%; the relapse incidence - RI at 9,2 y equaled 74% for patients with elevated b2m and 32% for those with b2m within normal range, p=0.02. Other factors included in multivariate analysis were: BM - pc ≥ 5% vs. &lt; 5% (100% vs. 55%, p=0.07) and MoP elevated vs. within normal limits (77% vs. 59%, p=0.1). The progression free survival - PFS was decreased in patients with elevated b2-mgl (29% vs. 68%, p=0.02), in these with BM - pc ≥5% (0% vs. 45%, p=0.03) and with elevated MoP (22% vs. 40%, p=0.1). Coincident observations in our MM patients suggest that elevated b2-mgl is more frequent in patients displaying 13q−. In multivariate analysis b2-mgl remained the only factor associated with increased risk of relapse (hazard ratio=3.29, p=0.03) and reduced probability of PFS (hazard ratio=3.29, p=0.03) Conclusion: Serum beta2-microglobulin before first autoHCT is a reliable independent predictor for RI and PFS duration in MM patients, ipso facto it is helpful in appraisal of patients who may benefit from myeloablative therapy followed by autoHCT.

Superior Complete Remission/Very Good Partial Remission Rate with Peri-Transplant Administration of Thalidomide-Dexamethasone for Newly Diagnosed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5474-5474
Author(s):  
Michele Cavo ◽  
Elena Zamagni ◽  
Patrizia Tosi ◽  
Delia Cangini ◽  
Paola Tacchetti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Induction Therapy ◽  
Partial Remission ◽  
Remission Rate ◽  
Remission Induction ◽  
High Dose ◽  
Newly Diagnosed ◽  
Negative Group ◽  
Positive Group

Abstract The “Bologna 2002” study was a phase 2 multicenter trial with thalidomide-dexamethasone (thal-dex) and double transplantation (Tx) of autologous peripheral blood stem cells (PBSCs) to support 2 sequential courses of high-dose melphalan (MEL) as up-front therapy for newly diagnosed patients with symptomatic multiple myeloma (MM). By study design, thal (200 mg/d) and pulsed dex (40 mg/d for 4 days, repeated monthly) were administered as primary remission induction therapy and were subsequently continued throughout the other treatment phases. An analysis was performed on the first 100 patients who were enrolled into the study. For comparison of their outcome, an equal number of pair mates were retrospectively selected among patients who entered the “Bologna 96” trial and received VAD as primary remission induction therapy followed by either single or double Tx. Case-matching was performed with respect to age (±2 years), serum β2-microglobulin (±1 mg/L) and clinical stage. The 2 groups of patients were also comparable with respect to the planned doses of cyclophosphamide (CTX, 7 g/m2) administered for PBSC collection and of MEL (200 mg/m2) given in preparation for first Tx. Aim of the present analysis was to evaluate whether administration of thal-dex (thal-positive group, “Bologna 2002” study) following CTX and first MEL increased the rate of response in comparison with the same treatments administered without added thal-dex (thal-negative group, “Bologna 96” study). Primary endpoint was the rate of complete remission (CR) + very good partial remission (VGPR), as calculated on an intent-to-treat basis at 30 days after CTX and at 90 days after first MEL (e.g. at which time thal-dex was discontinued). In the thal-positive group, the probability to attain ≥ VGPR increased from 21% after primary remission induction therapy to 38% after CTX and 63% after first MEL. The corresponding figures in the thal-negative group were 14%, 18% and 27%, respectively. Differences between the 2 groups in terms of ≥ VGPR rates after CTX and first MEL were statistically significant in favor of the thal-positive group (P=0.001 and &lt; 0.00000, respectively). Toxicity of thal was generally mild and well manageable. All patients but 7 continued planned daily thal and pulsed dex until the day before second Tx. Causes of thal discontinuation included deep vein thrombosis in a single patient, inadequate PBSC collection in 3 patients and granulocytopenia in 3 other patients. In conclusion, incorporation of thal-dex into a multiphase treatment program including CTX for PBSC collection and PBSC-supported MEL for newly diagnosed MM resulted in a significantly increased rate of CR + VGPR in comparison with the same treatments administered without added thal-dex. The objective of increasing the rate of ≥ VGPR by administering thal-dex following CTX and first Tx was achieved without the cost of increased toxicity. Whether these favorable results translated into extended overall survival still remains to be demonstrated; an analysis will be presented at the meeting.

Reduced-Intensity Conditioning for Allografting Following Autografting for Myeloma: Lower Relapse Rates Compared with Single or Double Autografting but Similar Overall Survival. The Genoa Experience in 74 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5095-5095
Author(s):  
A.M. Carella ◽  
G. Catania ◽  
S. Biasco ◽  
M. Congiu ◽  
S. Nati ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Progression ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Clinical Signs ◽  
Reduced Intensity Conditioning ◽  
Immunological Responses ◽  
Risk Of Disease ◽  
Reduced Intensity

Abstract Multiple Myeloma (MM) is the most frequent indication for autolografting and allografting. Autografting (AutoSCT) represents the most effective palliation for these patients. Even the double AutoSCT where there is demonstrated good long-term control in a minority of patients do not appear to result in cure of disease. Myeloablative AlloSCT is penalized by excessive transplant-related mortality (TRM) and toxicity.The introduction of reduced-intensity conditioning for allografting (RICT) has renewed interest in the use of AlloSCT for MM. Recent studies have reported encouraging results with tandem AutoSCT followed shortly thereafter by RICT in MM patients as compared to AutoSCT or myeloablative AlloSCT alone. Here we present the results achieved in our Unit in patients receiving AutoSCT (single or double) compared to patients receiving tandem AutoSCT/RICT. The major results are summarized in the table. In the AutoSCT/RICT group the risk of disease progression was reduced for those patients who achieved full chimerism, acute and/or chronic GVHD. This finding confirms the existence of a graft-versus-myeloma effects. Since the first clinical signs of response of remitters patients were noted between 70 and 120 days and maximum response between 160 and 200 days after RICT (and after DLI in 2 patients) these responses should be considered immunological responses. In conclusion, these data suggest that AutoSCT/RICT significantly reduces the incidence of disease progression but did not impact on overall survival with respect to single or double AutoSCT. Single Double AutoSCT AutoSCT AutoSCT + RICT (n=15) (n=35) (n=24) Age, median 64 (range 48–73) 62 (range 35–73) 50 (range 34–63) No. prior cycle chemoth., median 5 (range 3–8) 4 (range 3–6) 4 (range 3–6) Conditioning regimen for AutoSCT Melph. 200 mg/m2 Melph. 200 mg/m2 Melph. 200 mg/m2 Conditioning regimen for RICT ==== ==== TBI-Flu (19 pts) Flu-Melph. (5 pts) Days from Dx to AutoSCT, median 210 (range 120–390) 320 (range 120–840) Days from AutoSCT to RICT ==== ==== 80 Overall Survival 73,3% (11/15) 60% (21/35) 66% (16/24) Median Overall Survival 37 (range 10–132) 51 (range 13–147) 28 (range 6–87) Pts alive in CR 1 (6,6%) 4 (26,6%) 10 (41,6%) CR duration, median 20 mo. 56 mo. (range 28–70) 67 mo. (range 8–78) TRM 1 ==== 3

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