Comparative Analysis of Ablative and Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation in Treatment of Adult Patients with Chronic Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5414-5414
Author(s):  
Lidia Gil ◽  
Jan M. Zaucha ◽  
Jan Styczynski ◽  
Anna Czyz ◽  
Andrzej Hellmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Allogeneic Hsct ◽  
Sibling Donor ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Negative Outcome

Abstract Allogeneic HSCT remains the only curative therapy for chronic myelogenous leukemia (CML) patients. We compared results of myeloablative (MAB) and reduced intensity conditioning (RIC) HSCT from sibling donor in 62 pts with CML, treated between 2000 and 2005. In MAB group, 44 pts (median age 39.5, range 17–54 yrs) were conditioned with BuCy2 regimen. Thirty four pts were in chronic, 7 in acceleration and 3 in 2nd chronic phase. 26 pts received PBSC and 18 were grafted with bone marrow HSC. Transplanted material contained 3.8 (1.24–14.6) x 106/kg CD34+ cells. Prophylaxis of graft versus host disease (GVHD) consisted of cyclosporin (CsA) and methotrexate. Eighteen pts (median age 48, range 37–56 yrs) were treated with fludarabine-based RIC regimen. This group comprised 13 pts in chronic and 5 with accelerated phase. Patients were grafted with PBSC only, containing 4.75 (2.25–10) x 106/kg CD34+. CsA alone was given as GVHD prophylaxis. RIC group differ from MAB group by 2 factors: higher age (p<0.001) and higher EBMT pre-transplant (Gratwohl) risk score (p=0.028). Results: Hematopoietic recovery occurred in all pts in MAB group, and in 94% in RIC group. Probability of overall survival for all pts was OS=0.57±0.09. 31 pts developed acute GVHD ≥2 grade (21 in MAB and 10 in RIC) and 25 pts extensive chronic GVHD (18 in MAB and 7 in RIC). Mean survival, estimated 5-yrs OS, probabilities of GVHD incidence, relapse and treatment related mortality (TRM), estimated by Kaplan-Meier method, with respect to transplantation method, are shown in Table. TABLE: COMPARISON OF RESULTS IN MAB-HSCT AND RIC-HSCT Probability MAB-HSCT (n=44) RIC-HSCT (n=18) P Mean survival (years) 4.1 (95%CI=3.5–4.6) 2.1 (95%CI=1.1–3.0) Overall survival 0.78±0.07 0.24±0.13 0.0010 Relapse incidence 0.21±0.08 0.30±0.15 0.4069 Treatment related mortality 0.14±0.05 0.61±0.18 0.0108 Acute GVHD ≥ 2 0.51±0.08 0.64±0.12 0.9492 Chronic extensive GVHD 0.59±0.05 0.60±0.15 0.8344 Factors predicting negative outcome by Cox univariate analysis for all pts, were: AGVHD≥2 grade (p=0.0001, HR=2.78 95%CI=1.49–5.26), extensive CGVHD (p=0.0253, HR=3.83, 95%CI=1.01–14.6), female donor (p=0.0551, HR=1.54, 95%CI=0.99–2.40), pre-transplant risk score >2 (p=0.0053, HR=1.89, 95%CI=1.22–2.94) and RIC (p=0.0027, HR=1.96, 95%CI=1.26–3.03). Factors predicting negative outcome by multivariate analysis were: AGVHD≥2 (p=0.0001, HR=3.03, 95%CI=1.56–5.39), extensive CGVHD (p=0.0370, HR=2.75, 95%CI=1.17–6.49), pre-transplant risk score >2 (p=0.0507, HR=1.59, 95%CI=0.99–2.53) and RIC (p=0.0342, HR=1.64, 95%CI=1.17–6.49). Age >45 yrs did not predict for OS. In matched-pair analysis, identified by pre-transplant risk score and age, RIC group had lower OS (0.24±0.13 vs 0.88±0.08 p=0.0010), higher TRM (0.61±0.18 vs 0.06±0.05, p=0.0064), with no difference in AGVHD, CGVHD and relapse incidence, when compared to MAB group. In summary, this experience with sibling donor allogeneic HSCT in CML, demonstrates a similar incidence of AGVHD≥2 and extensive CGVHD in RIC and MAB groups, and more importantly, results of RIC-HSCT in adult CML are not satisfactory, mainly because of high treatment related mortality.

Reduced Intensity Conditioning Regimens with Alemtuzumab Result in Low Treatment-Related Mortality and Low Relapse Rate in Unrelated and Related Allotransplantation Recipients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5253-5253
Author(s):  
Carolyn L. Bigelow ◽  
Stephanie Elkins ◽  
Vincent Herrin ◽  
Cheryl L. Hardy ◽  
Joe Clark Files
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Relapse Rate ◽  
Acute Gvhd ◽  
Reduced Intensity Conditioning ◽  
Group 2 ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality ◽  
Group 1

Abstract From September, 2003, to July, 2006, 29 adult patients with hematological malignancies received reduced intensity conditioning (RIC) instead of standard conditioning for allogeneic transplant. The RIC regimens used in our program employ an ablative dose of melphalan and patients become cytopenic and transfusion-dependent. Patients were transplanted for a variety of malignancies including multiple myeloma, AML, CML, NHL, MDS, one renal cell carcinoma and one CLL. Eleven (38%) were in CR at time of transplant while 18 (62%) had relapsed or refractory disease. With a median follow-up of 8 mon (range 1–27 mon) we have completed a retrospective analysis of treatment-related mortality, d+100 and overall survival, engraftment, grades I-II and III-IV acute GVHD, and relapse rate. Two RIC regimens were used consecutively, consisting of either: fludarabine 30 mg/m2 × 5 d and melphalan 140 mg/m2 × 1 d in both groups, and Alemtuzumab 20 mg/d × 3d (Group 1) and × 2d (Group 2). Group 1 was 10 patients and Group 2 was 19. Median age was 53, range 24–66. Median age of Group 1 was 47 (range 24–59) and of Group 2 was 54 (range 34–66). Seventeen patients received MUD products (4 in Group 1 and 13 in Group 2) and twelve received MRD products. Cell source was bone marrow (8 patients), PBSC (18 patients) cord blood (2 patients) and combined products in 2 transplants (2 patients). All patients received an adequate C34+ cell dose or TNC dose (cord blood) and none of the products was manipulated. HLA matches were 6/6 antigen matches or better in Group 1 except for a 4/6 allele matched cord blood. All products were 6/6 or better in Group 2 except for two who were 8/10 allele matches, one 5/6 antigen match and a 4/6 serological match (cord). GVH prophylaxis was tacrolimus tapering after d+100 and MMF tapering after d+30. All patients except one achieved a WBC graft, and the ANC >500/dl occurred at a median of 12 d (range 10–48 d). The graft failure was a CML in Group 2 who received the 8/10 marrow product followed by a cord blood transplant that also failed. Eight (28%) of the cohort developed acute GVHD grades I-II (one from Group 1, 7 from Group 2) and two developed grades III-IV (one from each group). Five (17%) went on to develop chronic GVHD (one from Group 1, 4 from Group 2). Relapse or disease progression occurred in only 38% (4 in Group 1 and 7 in Group 2). Seven from the cohort were treated with one or more DLI to accelerate conversion to full chimerism and two from each group developed acute GVHD following the treatment. Incidence of treatment-related mortality by d+100 was low at 21%, with two patients in Group 1 and 4 in Group 2. Overall survival was 41%, 3 in Group 1 and 9 in Group 2. Most surprising was the overall survival of MUD patients, 41%, all from Group 2, which is higher than that reported by NMDP for unrelated transplants. In summary, we plan to continue accruing patients to both Alemtuzumab dosing regimens in order to compare the incidence of GVHD and relapse rate in each treatment arm. We conclude that a RIC regimen utilizing Alemtuzumab allows for a relatively low treatment-related mortality (21%), a low relapse rate (38%) and a superior survival (41%), especially in MUD transplants.

Myeloablative Conditioning Followed by T-Cell Depletion Is Associated with Low Treatment Related Mortality.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5221-5221
Author(s):  
Nicolas Novitzky ◽  
Valda Thomas ◽  
Cecile du Toit ◽  
Andrew McDonald
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Disease Recurrence ◽  
Haematological Malignancies ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Introduction: Classically the conditioning for transplantation in haematological malignancies has been with myeloablative doses of radiation or chemotherapy, and was followed by variable immunosuppression for the prevention of GvHD. This strategy has been associated with substantial transplant related mortality from regimen toxicity and GvHD, which were most pronounced in older patients. Reduced intensity conditioning programs that are mainly immunosuppressive allow engraftment and predisposed to donor chimerism and appear to have lower TRM, but seem associated to higher rates of GvHD and disease recurrence. To better apportion conditioning strategies for patients undergoing allogeneic stem cell transplantation, we studied the outcome of 81 patients who received similar GvHD prophylaxis with T-cell depletion and immunosuppression, after myeloablative conditioning. Patients & methods: Patients with haematological malignancies, in remission or still responsive to chemotherapy who had an HLA identical sibling were offered T-cell depleted stem cell grafts. Conditioning was with ablative doses of either chemotherapy or total body radiotherapy. Stem cells were mobilised into the blood (PBPC) with G-CSF (5–10ug/kg × 5) and grafts were harvested by large volume (30 litres) apheresis. GvHD prophylaxis was by ex vivo depletion of lymphocytes from the graft with CAMPATH-1 H antibodies followed by therapeutic doses of cyclosporin until day 90. End points were TRM, disease recurrence rate and overall survival time. Results: 90 consecutive patients with median age of 45 (17–62) years were studied. The diagnosis included acute leukaemia (ALL in 7) in CR in 38, myeloproliferative disorders in 16, lymphoproliferative diseases in 26 and multiple myeloma in 10. Post transplantation, patients with CML received, in addition, escalating doses of lymphocytes at 6 months (maximum 1 × 107/kg CD3) or imatinib for 12 months. Median CD34+ cell number was 2.7 (1–12.3) and the median dose of campath-1H was 10 (range 7.5–45) mg. Median time to engraftment was 11 days. Overall, 20 (22%) individuals died while treatment related mortality occurred in 17% (n= 15; VOD 3, infections in 8, pneumonitis in 1, EBV lymphoma in 1 and GvHD in 2). GvHD (> grade1) occurred in 7 patients, was controlled with further immunosuppression but lead to death from infections in 6. Disease recurrence was seen in 12, but 7 with CML or myeloma responded to DLI. At a median follow up of 688 days, 77 survive; 75% in unsustained remission. Conclusions: Myeloablative conditioning is well tolerated in patients receiving T-cell depleted grafts, and treatment related mortality of <20% can be expected consistently with this strategy. This information is useful to more precisely select patients who would benefit most from reduced intensity conditioning schedules.

Targeted immune depletion prior to reduced-intensity allogeneic stem cell transplantation results in rapid and complete donor chimerism with low treatment-related mortality

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6540-6540
Author(s):  
R. M. Dean ◽  
D. H. Fowler ◽  
S. M. Steinberg ◽  
J. Odom ◽  
J. Gea-Banacloche ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Post Transplant ◽  
Donor Chimerism ◽  
Reduced Intensity ◽  
Treatment Related Mortality ◽  
Related Mortality

6540 Background: Significant variation in host immune status may influence outcomes after reduced-intensity (RI) allogeneic stem cell transplantation (alloSCT). We have investigated a strategy of targeted immune depletion (TID) with conventional chemotherapy to deplete host T cells and achieve a minimal disease state prior to RI alloSCT. The aim of TID is to rapidly establish complete donor chimerism after RI alloSCT in order to potentiate a graft-versus-tumor (GVT) effect. In a prospective phase II trial (NIH 03-C-0077), we evaluated the effect of TID on donor chimerism, acute graft-versus-host disease (GVHD), and clinical outcome. Methods: Thirty-one patients (pts) with relapsed and refractory hematologic malignancies (NHL = 16; HL = 4; CLL/PLL = 4; MDS/AML = 3; other = 4) were enrolled. Median age was 57 years (range: 31–71). All pts received EPOCH-F (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine) ± rituximab (R) as TID to deplete host CD4+ cells <100/μL. All pts then received a RI conditioning regimen consisting of fludarabine and cyclophosphamide followed by a T-cell replete allograft from HLA-matched siblings. GVHD prophylaxis consisted of cyclosporine plus short-course mini-methotrexate. Results: EPOCH-F(R) achieved the target host T-cell level in 74% of pts. All 31 pts engrafted after RI alloSCT. Complete donor chimerism (> 95%) was observed in 74% and 81% of pts at day +14 and +28 post-transplant, respectively. The incidence of grade II-III acute GVHD was 42% with no cases of grade IV acute GVHD. The median potential follow-up from transplant is 25 months. Actuarial treatment-related mortality at 1 and 2 years was 3% and 8%, respectively. Event-free survival probabilities at 1 and 2 years post-transplant are 65% and 49%, respectively. Ten pts are alive and event-free >24 months post-transplant. The overall survival probabilities at 1 and 2 years are 84% and 64%, respectively. Conclusions: TID prior to RI alloSCT results in rapid, complete donor engraftment and may potentiate GVT effects. This treatment strategy was associated with very low TRM and favorable outcomes in an older patient population with advanced hematologic malignancies. No significant financial relationships to disclose.

Gvhd-Associated Early Impairment of Marrow Function Is Frequent after Allogeneic Transplantation and Is a Sensitive Biomarker for Prediction of Treatment Related Mortality and of Overall Survival

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1160-1160
Author(s):  
Giuseppe Milone ◽  
Giuseppe Avola ◽  
Maria Grazia Camuglia ◽  
Salvatore Leotta ◽  
Alessandra Cupri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Disease Status ◽  
Risk Of Death ◽  
Cd34 Cells ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract INTRODUCTION: Aim of our study was to determine the role of acute-GVHD in influencing early marrow function and whether assessment of “GVHD-associated marrow impairment” may predict transplant outcome. METHODS: We have prospectively studied 62 patients who received T-replete allogeneic stem cell transplantation because of various malignancies. At day +18/+19, we determined in bone marrow: CD34+ cells, frequency of clonogenic cell (CFU-GM and BFU-E) and, in 20 patients, also CD34+ cells showing apoptosis (AnnexinV/7-AAD). Results were related to acute-GVHD and to clinical outcome in terms of Treatment Related Mortality (TRM), Relapse Rate (RR) and Overall Survival (OS). To distinguish the effect of a-GVHD from that determined by corticosteroid, patients were divided in three groups according to time of presentation of a-GVHD: “Early a-GVHD, “No a-GVHD” and “Impending a-GVHD”. The latter group consisted of patients presenting a-GVHD after engraftment. RESULTS: In univariate analysis “Febrile neutropenia” and” Acute GVHD” were important factors for a reduction of frequency of marrow clonogenic cells assessed on day +18/+19. However, in multivariate analysis only “Acute GVHD” was able to influence frequency of marrow CFU-GM and BFU-E at day +18/+19. Patients not developing “a-GVHD” until day +90, had on day+18 a median growth of CFU-GM of 202/10e5 plated cells while patients suffering “early GVHD” had a marrow CFU-GM growth significantly reduced: 82/10e5 plated cells, (p= 0.0009). Median CFU-GM was found significantly reduced also in patients defined as “impending GVHD” (onset of a-GVHD at day +20-/+90) (p=0.01). Apoptotic CD34+ cells in marrow cells at day +18/+19 were inversely correlated to frequency of marrow BFU-E (r= -0.5, p=0.04). Taking into account competing risks, Cumulative Incidence of TRM at 2 y in the group of patients having a frequency of marrow CFU-GM over median was 5% while it was 30% in the group having CFU-GM below the median (log-rank: p=0.004). Cumulative incidence of Relapse was not significantly different in these two groups (31% versus 34%). OS was significantly better in group having CFU-GM over median: 62% versus 35% (logrank: p=0.02). Frequency of CFU-GM over median at day +18/+19 was a factor important for a reduced risk of death (HR=0.358; p=0.004) also after adjusting, using multivariate Cox analysis, for Disease Status (Early versus Advanced). CONCLUSIONS: acute-GVHD impairs early and significantly marrow function, marrow-GVHD is a sensitive biomarker for prediction of TRM and OS. Disclosures No relevant conflicts of interest to declare.

The Comparison of Myeloablative Versus Reduced Intensity Conditioning Regimen in ABO Mismatched Allogeneic Hematopoietic Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5146-5146
Author(s):  
Pervin Topcuoglu ◽  
Mutlu Arat ◽  
Tugce Bolukbasi ◽  
Ender Soydan ◽  
Yesim Ozer ◽  
...  
Keyword(s):  
Blood Group ◽  
Acute Gvhd ◽  
Pure Red Cell Aplasia ◽  
Red Cell ◽  
Reduced Intensity Conditioning ◽  
Red Cell Aplasia ◽  
Abo Incompatibility ◽  
Reduced Intensity ◽  
Related Mortality

Abstract Recently, in an effort to reduce the transplant related mortality, AHCT with reduced intensity conditioning (RIC) have been developed. It has been reported that patients receiving RIC from an ABO-mismatched donor had more transplant-associated complications compared to ablative AHCT (BMT2001;28: 315, Transfusion2002; 42:1293, Transfusion2003; 43: 1153). In this single center, retrospective, historical case-matched study, we aimed to analyze the influence of ABO-incompatibility on transplant-related morbidity and mortality between ablative and RIC. Between 1988 and 2003, 39 patients underwent AHCT with RIC and only 14 were ABO-incompatible. Ten patients with ABO-incompatibility and having a regular follow-up for blood group typing were evaluated for immuno-hematological complications, such as acute or delayed-type hemolysis (DTH), pure red cell aplasia (PRCA), thrombotic thrombocytopenic purpura (TTP) and early transplant-related complications, were compared to 20 case control recipients having matched pretransplant characteristics and similar follow up, but myeloablative regimen, either bone marrow (BM) or peripheral blood (PB) stem cells infused. Patients’ characteristics are shown in table below. All the recipients and donors underwent a detailed pretransplant work up and all the recipients were followed twice a week post transplant by a transfusion specialist according to guidelines (BMT, 2001;28:315). Median follow-up was 195 days (range, 51–538d). We did not observe any acute hemolysis, but 11 experienced DTH. No significant differences were encountered among the three groups in terms of DTH (p=0.356). In all recipients having a major ABO incompatibility, the blood group switched to donor type, but 50% of the patients with minor ABO-incompatibility still had either their antigen persistency or the appearance of donor-derived isoagglutinins. We observed mild (n=1, BM group) and severe pure red cell aplasia (n=1, RIC group) in two patients having a major ABO-incompatibility. TTP was developed in one patient with major ABO-incompatibility. In conclusion, we did not observe any difference between ablative AHCT and RIST in ABO incompatible patients in terms of immuno hematological complications in contrast to published case series. In addition, we could not show any negative impact of ABO-incompatibility on the severity of acute GVHD and the rate of early transplant related mortality. Table Conditioning Ablative Reduced Intensity Source (patients) PB (n=10) BM (n=10) PB (n=10) Gender (M/F) 2/8 6/4 5/5 Median age (range) 34 (16–45) 31 (17–46) 33 (21–47) Diagnosis CML (2), AML (7), other (1) CML (2), AML (6), other (2) CML (4), AML (1), other (5) ABO-incompatibility Major 5 6 5 Minor 5 4 5 Delayed type hemolysis 5 (50%) (22,23,55,90,120) 2 (20%) (18,27) 4 (40%)(20,130,165,188) RBC transfusion (100 days) 3 (0–15) 4 (0–10) 5 (0–10) Median days of the independence from pRBC 7 (0–31) 18 (0–41) 7 (0–28) Median follow-up (days) 195 (90–538) 194 (63–467) 200 (51–511) Acute GVHD (grade II–IV) n (%) 3 (30%) 4 (40%) 4 (40%) TRM 100, n (%) 1 (%10) 1 (%10) 1 (%10)

scholarly journals Improved Treatment-Related Mortality and Overall Survival of Patients with Grade IV Acute GVHD in the Modern Years

2016 ◽  
Vol 22 (5) ◽  
pp. 910-918 ◽  
Author(s):  
Areej El-Jawahri ◽  
Shuli Li ◽  
Joseph H. Antin ◽  
Thomas R. Spitzer ◽  
Philippe A. Armand ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Gvhd ◽  
Treatment Related Mortality ◽  
Related Mortality

scholarly journals Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study

Blood ◽  
2012 ◽  
Vol 119 (9) ◽  
pp. 2141-2148 ◽  
Author(s):  
Junya Kanda ◽  
Masakatsu Hishizawa ◽  
Atae Utsunomiya ◽  
Shuichi Taniguchi ◽  
Tetsuya Eto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Cell Leukemia ◽  
Graft Versus Host ◽  
Adult T Cell Leukemia ◽  
Grade 3 ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ATL patients who received allogeneic HCT and survived at least 30 days posttransplant with sustained engraftment. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that the development of grade 1-2 acute GVHD was significantly associated with higher overall survival (hazard ratio [HR] for death, 0.65; P = .018) compared with the absence of acute GVHD. Occurrence of either grade 1-2 or grade 3-4 acute GVHD was associated with lower disease-associated mortality compared with the absence of acute GVHD, whereas grade 3-4 acute GVHD was associated with a higher risk for treatment-related mortality (HR, 3.50; P < .001). The development of extensive chronic GVHD was associated with higher treatment-related mortality (HR, 2.75; P = .006) compared with the absence of chronic GVHD. Collectively, these results indicate that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of allografted patients with ATL.

Prolongation of Post Relapse and Overall Survival in Patients with Multiple Myeloma by Salvage Strategy with the Combination of Thalidomide and Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation Based on the Nature of Disease Progression after Autologous Bone Marrow Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3494-3494
Author(s):  
Izhar Hardan ◽  
Avichai Shimoni ◽  
Abraham Kneller ◽  
Abraham Avigdor ◽  
Noga Shemtov ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Reduced Intensity Conditioning ◽  
Duration Of Response ◽  
Reduced Intensity ◽  
Related Mortality

Abstract The impact of the use of autologous BMT (ABMT) as an up-front therapy on the natural history of multiple myeloma (MM) is limited, mainly due to the course of disease at progression after ABMT. Conventional salvage at that stage was reported to offer overall survival of only 14–17 months. The benefit of thalidomide and reduced intensity allogeneic stem cell transplantation (RIC SCT), which were introduced at that stage, is limited by the duration of response and toxicity. It was shown, however, that the aggressiveness of relapse clearly predicts for outcome in this set-up. Methods. Patients (pt’s) with progression after ABMT were treated according to a strategy based on the nature of relapse, with thalidomide (Thal) and reduced intensity conditioning allogeneic stem cell transplantation (RIC SCT) as following: all progressing patients had Thal ± Dexa for induction of response, but only at a clinical indication for therapy. DTPACE combination was given to those who failed to respond to Thal. Pt’s with aggressive progression were offered a RIC SCT at response, while patients with an indolent progression were offered a RIC SCT only at escape from response to Thal or if being resistant to Thal+Dexa. Re-induction therapy was delivered prior to transplant. The post transplant therapy included DLI and/or Thal according to the findings in minimal residual disease (MRD) studies and base line chromosomal studies. Results. Seventy five pts (age 36–66, median 58 y) with indolent (n= 46, 61%) or aggressive (n=29, 39%) progression, were treated according to this strategy. The overall response rate (= or &gt;PR) to Thal ± Dexa was 58.6%. Thirty six pt’s (48%) subsequently underwent RIC SCT (27 related, 9 unrelated donor) and 10 pts with an indication but no matched donor had a 2nd ABMT. Treatment related mortality was 9.3% (7 pt, all after RIC SCT, giving transplant related mortality rate of 16.6% for RIC SCT in this setting). RIC SCT reversed resistant to Thal in 7 pt. The median overall survival (OS) from progression of the entire group is 39 months with a projected 3-years survival rate of 52% (follow-up 19m-74m, median= 34m). The nature of relapse was found to be a strong independent favorable prognostic factor with a median post relapse OS of &gt;62m (not yet reached) vers. 24m, for pt’s with indolent compared with aggressive relapse (p=0.00002). In 24 patients (32%), the duration of response exceeded the first progression free period (from ABMT until progression). The median OS from ABMT of this group of patients is 85m, compared with a median OS rate of 56m from ABMT in a comparable historical group of 62 patients from our center that relapsed after ABMT prior to the introduction of the Thal /RIC SCT strategy. Conclusion. The therapy with Thal and RIC SCT with a strategy based on the nature of disease progression after ABMT can improve post relapse and overall survival of MM patients. This may significantly add to the contribution of ABMT to the outcome of therapy in MM.

Equivalent Survival Following Fludarabine/Melphalan Reduced Intensity Conditioning with or without Rabbit ATG As Part of GvHD Prophylaxis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1959-1959
Author(s):  
J. Mark Prichard ◽  
Samatha Muppidi ◽  
Christopher R Flowers ◽  
Jonathan L. Kaufman ◽  
Mary Jo Lechowicz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Acute Gvhd ◽  
Conditioning Regimen ◽  
Donor Cell ◽  
Hematologic Malignancies ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Gvhd Prophylaxis ◽  
Reduced Intensity

Abstract Abstract 1959 Introduction: Reduced intensity conditioning (RIC) prior to allogeneic transplantation allows donor cell engraftment with the maintenance of a graft versus malignancy effect. A recent CIBMTR registry study suggested worse outcomes for patients receiving anti-thymocyte globulin (ATG) as part of the conditioning regimen. To further study the role of ATG when added to a fludarabine and melphalan RIC regimen in the unrelated donor (URD) setting, we have retrospectively studied 76 consecutive patients with advanced hematologic malignancies who underwent URD transplantation. Comparisons were made between cohorts that did or did not receive ATG (given primarily for HLA disparity) for pretransplant graft vs. host disease (GvHD) prophylaxis. Pateints and Methods: Seventy six patients with advanced hematologic malignancies (43% CIBMTR high-risk) received fludarabine and melphalan (FluMel) conditioning with or without pre-transplant rabbit ATG 6 mg/kg as part of GvHD prophylaxis. Twenty five patients who received ATG (24 of whom received grafts from donors mismatched at 1 or 2 HLA loci) were compared with 51 patients who did not receive ATG (45 of whom received grafts from HLA matched donors with six donors mismatched at a single locus). The majority of patients received post-transplant tacrolimus with either methotrexate (MTX) or mycophenolate mofetil for GvHD prophylaxis. With the exception of HLA disparity, pre-transplant patient characteristics were similar between groups (Figure 1). Results: With median follow up of 481 days and 376 days for the ATG and no ATG cohorts, respectively, K-M overall survival estimates were similar, with 2 year OS of 62 vs. 47 percent, respectively, for the ATG vs no ATG groups (p=.34). On multivariate analysis, the inclusion of MTX in GvHD prophylaxis was favorably associated with overall survival (p=.004), and was associated with a significant reduction in the incidence of severe (gr 3–4) acute GvHD (p=.03). There were no significant differences in pre-transplant creatinine, age, or comorbidity index scores between patients who did or did not receive MTX. Conclusions: Fludarabine and melphalan RIC, with or without pre-transplant ATG, produced similar outcomes following URD transplantation, despite the fact that patients receiving ATG in this series were more likely to have received a HLA mismatched graft. The inclusion of MTX for GVHD prophylaxis resulted in less severe acute GVHD and better survival when compared with tacrolimus/MMF. Disclosures: Flowers: Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy; Millennium/Takeda: Research Funding; Wyeth: Research Funding; Novartis: Research Funding. Kaufman:Merck: Research Funding; Keryx: Consultancy; Novartis: Consultancy; Onyx Pharmaceuticals: Consultancy; Millenium: Consultancy; Celgene: Research Funding. Lonial:Millennium Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Onyx: Consultancy; Merck: Consultancy. Sinha:Celgene: Research Funding.

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