Reduced Intensity Versus Myeloablative Conditioning for Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia

Abstract Introduction Reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (SCT) offer a potential treatment for otherwise incurable cases of acute myelogenous leukemia (AML) with less associated toxicity compared to myeloablative conditioning (MAC). Eradication of malignant cells after RIC depends largely on the graft-versus leukemia effect (GVL). These regimens are becoming increasingly popular, particularly in older patients or those with comorbidities. They may also be offered to otherwise healthy patients based on personal or physician preference, as there is growing evidence that overall survival may be equivalent for both treatments. We retrospectively reviewed the charts of Saskatoon Cancer Centre patients receiving either RIC or MAC to compare the incidence and grade of graft versus host disease (GVHD), progression free survival (PFS), and overall survival (OS). Methods We identified 74 patients who underwent HSCT for AML in complete remission (CR) between January 2000- December 2013. Of these patients, 55 received MAC and 19 received RIC. Median age at HSCT was 48 years (range 18-68). In the group receiving MAC, 36% of patients were >50 years, whereas 74% of patients receiving RIC were >50 yrs of age. Results Patients receiving RIC experienced greater incidence of chronic GVHD (63% vs 41%, p=.09) and relapse (54% vs 30%, p=.07). Incidence of acute GVHD was the same for either regimen (53%). Median overall survival was similar (39 vs 38 months), with lower early mortality in RIC later overtaking MAC at 27 months. Progression free survival demonstrated a non-statistically significant advantage for MAC (median 43 vs 49 months). Conclusion RIC has been associated with greater incidence of chronic GVHD and relapse, with no difference in overall survival. Patients receiving RIC are more likely to be >50 years of age, making comparisons challenging. The results of this review suggest that MAC is the preferred regimen for patients who can tolerate its toxic effects due to reduced incidence of chronic GVHD and relapse, however the similarity in overall survival makes the choice of either conditioning regimen reasonable. Future studies to identify the best conditioning regimen are warranted. Overall Survival Figure 1 Figure 1. Progression Free Survival Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality

Blood ◽

10.1182/blood-2002-04-1150 ◽

2002 ◽

Vol 100 (12) ◽

pp. 3919-3924 ◽

Cited By ~ 135

Author(s):

Nicolaus Kröger ◽

Herbert Gottfried Sayer ◽

Rainer Schwerdtfeger ◽

Michael Kiehl ◽

Arnon Nagler ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Antithymocyte Globulin ◽

Chronic Gvhd ◽

Progression Free Survival ◽

Reduced Intensity Conditioning ◽

Free Survival ◽

Reduced Intensity

We investigated the feasibility of unrelated stem cell transplantation in 21 patients with advanced stage II/III multiple myeloma after a reduced-intensity conditioning regimen consisting of fludarabine (150 mg/m2), melphalan (100-140 mg/m2), and antithymocyte globulin (ATG; 10 mg/kg on 3 days). The median patient age was 50 years (range, 32-61 years). All patients had received at least one prior autologous transplantation, in 9 cases as part of an autologous-allogeneic tandem protocol. No graft failure was observed. At day 40 complete donor chimerism was detected in all patients. Grade II to IV acute graft-versus-host disease (GVHD) was seen in 8 patients (38%), and severe grade III/IV GVHD was observed in 4 patients (19%). Six patients (37%) developed chronic GVHD, but only 2 patients (12%) experienced extensive chronic GVHD. The estimated probability of nonrelapse mortality at day 100 was 10% and at 1 year was 26%. After allografting, 40% of the patients achieved a complete remission, and 50% achieved a partial remission, resulting in an overall response rate of 90%. After a median follow-up of 13 months, the 2-year estimated overall and progression-free survival rates are 74% (95% CI, 54%-94%) and 53% (95% CI, 29%-87%), respectively. A shorter progression-free survival was seen in patients who already experienced relapse to prior autograft (26% versus 86%, P = .04). Dose-reduced conditioning with pretransplantation ATG followed by unrelated stem cell transplantation provides durable engraftment and donor chimerism, reduces substantially the risk of transplant-related organ toxicity, and induces high remission rates.

Download Full-text

Haploidentical Stem Cell Transplantation after Myeloabaltive Conditioning Is a Valid and Safe Option for Young Patients with Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma: A Study Compared with HLA-Matched Transplant

Blood ◽

10.1182/blood.v128.22.5849.5849 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5849-5849

Author(s):

Haiwen Huang ◽

Xiaofang Xiao ◽

Jia Chen ◽

Zhengming Jin ◽

Xiaowen Tang ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Young Patients ◽

Progression Free Survival ◽

Hematopoietic Stem ◽

Free Survival

Abstract Purpose: The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) therapy for refractory or relapsed (R/R) aggressive non-Hodgkin lymphoma (NHL) patients was still unknown. In this study, we aimed to explore the clinical outcome of R/R aggressive NHL patients received haplo-HSCT treatment. Patients and Methods: 23 R/R aggressive NHL patients who had undergone haplo-HSCT in our center between February 2006 and October 2015 were retrospectively analyzed, and 25 R/R aggressive NHL patients who received HLA-matched HSCT at the same period were also involved in this study. All patients received myeloablative conditioning (MAC) regimen, and antithymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. 12 patients had experienced autologous HSCT prior to allo-HSCT. Results: The median age of the total 48 patients was 33 (16-58) years old, and there were 33 males and 15 females in the total cohorts. The diagonosis were as following: 16 (33%) diffuse large B cell lymphoma and 22 (46%) peripheral T cell lymphoma. There were no difference in sex, age at transplantation, histologic diagnosis, aaIPI score, previous ASCT and conditioning regime between HLA-matched HSCT and Haplo-hsct groups. 44 patients had achieved engrafment, and the median times to neutrophil and platelet recovery were 12 and 15 days, respectively. Incidences of grade 3-4 acute GVHD were 18.3% in haplo-HSCT group and 16.7% in HLA-matched HSCT groups(p=0.87), while 2 years cumulative incidences of chronic GVHD in these two groups were 43.5% and 36.7% (P=0.68). For 16 patients who had chemoresistant disease at transplantation in haplo-HSCT group, four patients achieved complete remission, and ten patients achieved partial remission, while the other two patients experienced disease progression at 21 days and 37 days, respectively. With a median follow-up of 25 months, 12 patients experienced disease recurrence or progression in haplo-HSCT. And four patients died of transplantation related mortality: infection (n=2); acute GVHD (n=1) and multi-organ failure (n=1). There were no differences in overall survival (OS) rate at 2 years (52.8% vs 57.0%, P=0.85) and 2 years progress free survival (PFS) rate (52.7% vs 56.9%, p=0.73) between the haplo-SCT and HLA-matched SCT groups. Multivariate analyses suggested that old age (>45 years)(p=0.02), primarychemorefractory (p=0.04)and occurrence of grade3-4 aGVHD (p=0.01) may contribute to poor prognosis. Conclusion: Haploidentical hematopoietic stem cell transplantation withmyeloablative conditioning regimenachieved satisfactory outcome with acceptable side-effects. This approachcan be a feasible and acceptabletherapy for young patients withR/R NHLwho have no access to a HLA-matched donor. Figure Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Figure. Comparison of outcomes after haplo-SCT and HLA-matched SCT. (a) Overall survival, (b) Progression-free survival, (c) Cumulative incidences of grade3-4 acute GVHD, (d) cumulative incidences of chronic GVHD, (e) cumulative incidences of relapse, (f) cumulative incidences of non-relapse mortality. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Durable Engraftment with Minimal Toxicities after Allogeneic Hematopoietic Stem Cell Transplantation with a Reduced-Intensity Regimen Incorporating Fludarabine and 8 mg/kg Busulfan.

Blood ◽

10.1182/blood.v108.11.5246.5246 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5246-5246

Author(s):

Naoyuki Uchida ◽

Takahiro Fukuda ◽

Atsushi Wake ◽

Sung-Won Kim ◽

Kazuhiro Masuoka ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Disease Progression ◽

Cell Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Hematopoietic Stem ◽

Increased Risk ◽

Reduced Intensity

Abstract Background: The optimal regimen for allogeneic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) needs to be established. Therefore, we retrospectively reviewed data of 84 patients who underwent RIST using 180 mg/sqm fludarabine and 8 mg/kg busulfan (Flu/Bu8). All patients received mobilized blood stem cells from a related donor between Nov. 2000 and Jun. 2005. Patients and Methods: The median age of the patients was 53 years (range, 25–65). The diagnosis included 42 AML/MDS, 34 lymphoma and 8 others. Sixty-nine patients (82%) had high-risk diseases, including 56 (81%) in non-remission status before RIST. All were serologically 6/6 matched pairs, except for one who had a 5/6 match. For GVHD prophylaxis, 61 used cyclosporine A (CSP) alone, 21 used CSP + methotrexate (MTX), and 2 used some other compounds. Results: The engraftment kinetics were remarkable since all of the patients successfully engrafted at a median of 11 days (5–24 days), with no late graft rejection. Toxicities of grade 2 or 3 according to CTCAE v.3 were observed at minimal frequencies, i.e. 38 mucosal, 35 hepatic, 13 GI tract, 12 renal, 2 cardiac, 1 pulmonary, 19 febrile neutropenia, and 9 documented infections, and there were no grade 4 toxicities. The administration of MTX increased the incidence and severity of stomatitis (P=0.05). The cumulative incidences of grade II–IV and III–IV acute GVHD were, respectively, 50% and 29%, and 76% experienced chronic GVHD. Seventy-three patients (87%), including 38 of the 56 patients who were not in CR at the time of transplant, achieved partial or complete remission. The median follow-up of surviving patients was 1349 days (34–1981 days), and the day-100 mortality was 11% (disease progression 6% and non-relapse mortality [NRM] 5%). The 5-year overall and progression-free survival rates were 36% and 30%, respectively. Among 46 total deaths, 27 were from disease progression and 19 were from NRM primarily related to GVHD. The patients in remission at transplant showed better overall survival than those who were not in remission (85 % vs 34 % at 5 years post-transplant, respectively, P<0.05). The 5-year overall survival was 85 % for those in remission at transplant and 34 % for the remaining patients (P<0.05). Multivariate analyses showed that age older than 52 years and non-CR status at transplant were associated with an increased risk for mortality after RIST. Conclusions: Our study showed that RIST with this Flu/Bu8 regimen is feasible with durable engraftment and low early mortality. The clinical response rate is adequate for those who stayed in remission at transplantation, but otherwise a novel approach to prevent disease progression should be developed.

Download Full-text

Plasmablastic Morphology Is an Independent Predictor of Poor Survival After Autologous Stem-Cell Transplantation for Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.5.1551 ◽

1999 ◽

Vol 17 (5) ◽

pp. 1551-1551 ◽

Cited By ~ 46

Author(s):

S. Vincent Rajkumar ◽

Rafael Fonseca ◽

Martha Q. Lacy ◽

Thomas E. Witzig ◽

Terry M. Therneau ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Survival Time ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Independent Predictor ◽

Progression Free Survival ◽

Poor Survival ◽

Free Survival

PURPOSE: To study the prognostic value of plasmablastic morphology after autologous stem-cell transplantation for relapsed or primary refractory myeloma. PATIENTS AND METHODS: Seventy-five patients were studied. Investigators blinded to the clinical details of the individual cases reviewed bone marrow aspirate slides to determine plasmablastic classification. Plasmablasts were defined using strict, well-described criteria. Plasmablastic morphology was considered to be present (plasmablastic myeloma) when 2% or more plasmablasts were present in the plasma-cell population. RESULTS: Patients underwent transplantation 5 to 88 months (median, 20 months) after the initial diagnosis of myeloma. Twenty-eight percent of patients had plasmablastic morphology. A significantly greater proportion of patients with plasmablastic morphology had abnormal cytogenetics compared with those with nonplasmablastic classification (73% v 31%, respectively; P = .003). The overall survival rate measured from the time of transplantation was significantly worse in patients with plasmablastic morphology compared with those without (median survival time, 5 months v 24 months, respectively; P < .001). Progression-free survival time was shortened also, with a median time of 4 months compared with 12 months, respectively (P < .001). In the multivariate analysis, plasmablastic classification was the most powerful prognostic factor after transplantation for both overall (P = .001) and progression-free survival rates (P < .001). We also identified three risk groups based on plasmablastic morphology: plasma-cell labeling index, lactate dehydrogenase, and cytogenetics. The median overall survival time was 38 months when none of these factors was abnormal, 17 months with one abnormal factor, and 8 months with two or more abnormal factors (P < .001). CONCLUSION: Plasmablastic morphology is a powerful independent predictor of poor survival rate after autologous stem-cell transplantation for relapsed or primary refractory myeloma.

Download Full-text

Reduced Intensity Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma Is Associated with Substantial Late Transplant Related Mortality and a Poor Outcome in Patients with Chemoresistant Disease.

Blood ◽

10.1182/blood.v104.11.2260.2260 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2260-2260 ◽

Cited By ~ 3

Author(s):

Stephen P. Robinson ◽

Norbert Schmitz ◽

Goli Taghipour ◽

Anna Sureda

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Progression Free Survival ◽

High Dose ◽

Free Survival ◽

Mantle Cell ◽

Reduced Intensity ◽

Related Mortality

Abstract The prognosis for patients with mantle cell lymphoma (MCL) treated with conventional chemotherapy remains poor. Dose escalation and stem cell transplantation has been increasingly employed in an attempt to improve the outcome in these patients. However, due to the advanced age of many patients with MCL, high dose therapy and allogeneic stem cell transplantation is particularly hazardous. Reduced intensity allogeneic transplantation (RIT) may reduce the toxicity of allogeneic stem cell transplantation, facilitate allogeneic engraftment and graft versus lymphoma reactions. However, the results reported to date with this treatment modality have been based on small numbers of patients and provide conflicting results. We have therefore analysed the outcome of a large cohort of patients with MCL reported to the EBMT registry who have undergone RIT. A total of 144 patients (123 male) with a histological diagnosis of MCL were reported by 81 centres. The median age at transplant was 49 years (range 28–68 years) and the median time from diagnosis to transplant was 25 months (range 0.25–13.2 years). The patients had received a median of 2 (range 1–5) lines of prior chemotherapy and 60 (42%) had undergone a prior high dose procedure. At the time of RIT 100 patients had chemosensitive disease, 22 chemoresistant disease and 22 had untested relapse. Patients underwent conditioning with reduced intensity regimens prior to transplantation with allogeneic peripheral blood stem cells (122), bone marrow (20) or both (1). Fully matched sibling donors were used in 109 cases, matched unrelated donors in 21 and 9 patients received mismatched stem cells. 123 of 126 patients assessable for engraftment demonstrated sustained engraftment. With a median follow up of 9 months 84 patients remain alive and 60 have died (15 from progressive disease and 45 from non-relapse mortality). The transplant related mortality (TRM) was 12% at 100 days but by Kaplan-Mier analysis the TRM was 35% at 1 year and 50% at two years. In univariate analysis there was a non-significant trend to a higher TRM in patients with chemoresistant disease (p=0.067) and those with a prior transplant (p=0.062). Patient age and the number of lines of prior therapy had no impact on TRM. At two years following transplant 57% of patients had evidence of disease relapse or progression which was significantly worse in those with chemoresistant disease prior to transplant (p=0.02). The overall survival (OS) at 1 year and 2 years was 55% and 31% respectively and was worse for patients with chemoresistant disease. The progression free survival (PFS) at 1 and 2 year was 43% and 26% respectively. Only disease status at transplantation predicted for a worse PFS. Acute GVHD (grade II-IV) developed in 52 patients and chronic GVHD in 23 patients. Although the early transplant related toxicity is low there remains a significant TRM following RIT for MCL and consequently a low progression free survival. Patients with chemoresistant disease have a particularly poor outcome.

Download Full-text

Concurrent Fludarabine and Cyclophosphamide As a Reduced Intensity Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation Ablates Host T-Cells and Results in Rapid Full Donor Chimerism

Blood ◽

10.1182/blood.v118.21.1937.1937 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1937-1937

Author(s):

Rachel B. Salit ◽

Michael R. Bishop ◽

Steven Z. Pavletic ◽

Frances T. Hakim ◽

Seth M. Steinberg ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Conditioning Regimen ◽

Reduced Intensity Conditioning ◽

Myeloablative Conditioning ◽

Hematopoietic Stem ◽

Donor Chimerism ◽

Conditioning Regimens ◽

Reduced Intensity

Abstract Abstract 1937 Background: Reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) is associated with decreased transplant-related mortality (TRM). However, RIC-HSCT is typically associated with higher rates of mixed chimerism and graft rejection compared to myeloablative conditioning. Host T-cell immunity has been demonstrated to be an important predictor of engraftment and establishment of full donor chimerism in clinical studies. It was previously demonstrated in murine models that concurrent fludarabine (F) and cyclophosphamide (C) ablated host T-cells to the extent of myeloablative total body irradiation with reduced myeloid cell toxicity and prevented rejection of fully MHC-disparate marrow allografts (Petrus et al, BBMT, 2000). While fludarabine and cyclophosphamide are agents commonly used in reduced intensity conditioning regimens, their concurrent use has never been reported. Here, we analyze results from 102 patients who received the reduced intensity conditioning FC regimen in the setting of matched related or unrelated allogeneic stem cell transplantation. Methods: On four consecutive protocols at the National Cancer Institute, hematologic malignancy patients received induction chemotherapy followed by the FC regimen: fludarabine 30 mg/m2/d, days −6 to −3 and cyclophosphamide 1200 mg/m2/d, days −6 to −3. Peripheral blood stem cells were infused on Day 0. GVHD prophylaxis was either a calcineurin inhibitor alone or in combination with other agents. Results: 102 patients (females, 36; males, 66) were enrolled on study. Median age was 50 yrs (range, 21–71). Diagnoses included AML/MDS (n = 2), HL (n = 12), DLBCL (n = 35), CLL (n = 13), FL (n = 12), MCL (n = 10) and TCL (n = 10). Median number of prior regimens = 3 (range, 1 – 9); 25 patients had prior autologous transplant. Transplants were performed using HLA - matched sibling donors (n = 82) or 10/10 matched unrelated donors (n = 20). At the time of study entry, disease status was defined as chemosensitive (n = 53) or chemorefractory (n = 49). Patients were in CR (n = 19), PR (n = 26), SD (n = 37), or PD (n = 19); one patient was not evaluable. 101 of 102 patients (99%) proceeded to transplant. Median CD3+, CD4+, and CD8+ lymphocyte counts after induction chemotherapy (pre-FC conditioning) were: 150 cells/μl (1–1557), 80 cells/μl (0–1332), and 52 cells/μl (52–1195), respectively. Following FC conditioning, median CD3+, CD4+, and CD8+ counts were: 3 cells/μl (0–65), 3 cells/μl (0–93), and 0 cell/μl (0–22) (each p< 0.0001). All patients engrafted. Median time to neutrophil engraftment (ANC > 500) was 10 days and platelet engraftment (plt > 20 48 hours post transfusion) was 11 days. At Day +14, median CD3+ chimerism was 100% (range 30–100%), CD14+/15+ chimerism was 100% (range 6–100%), and whole blood chimerism was 100% (range 11–100%). Patients maintained full donor chimerism as evidenced by median 100% (range 50–100%) whole blood chimerism at Day +100. By Day +28 post-transplant, 41 patients (40%) achieved (n=24) or maintained (n=17) a CR and 38 patients (37%) achieved or maintained a PR for an overall response rate of 77%. Fourteen patients had SD and 4 had PD. Day +100 and one year TRM were 7% and 15% respectively. With a median follow-up of 92.4 months, 1 yr and 2 yr EFS were 52% and 41% and 1 yr and 2 yr OS were 68% and 58% respectively. Both EFS (p = 0.0003) and OS (p = 0.01) were significantly associated with response to FC. Acute GVHD grades II-IV and III-IV occurred in 56% and 23% of patients respectively. The rate of chronic GVHD was 65%. Grade IV non-hematologic toxicities as of Day +28 post-transplant included cardiac (n = 7, n = 1 Grade V), pulmonary (n=9), GI (n=9), and neurologic (n=3). While 62% of patients had at least one Grade III infection, only 2 patients had a Grade IV infection. Conclusion: The concurrent FC conditioning regimen resulted in host T-cell ablation and rapid full donor chimerism characteristic of myeloablative conditioning regimens. Furthermore, RIC-HSCT using concurrent FC achieved a high rate of complete remissions with an acceptable safety profile. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Impact of Different Mobilization Methods on Graft Composition and Outcome after Autologous Stem Cell Transplantation: Implications for Upfront Use of Plerixafor

Blood ◽

10.1182/blood.v124.21.1125.1125 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1125-1125

Author(s):

LaQuisa Hill ◽

Oluchi C. Ukaegbu ◽

Bipin N. Savani ◽

Salyka Sengsayadeth ◽

Stacey Goodman ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Partial Remission ◽

Progression Free Survival ◽

Free Survival ◽

Disease Response ◽

Graft Composition

Abstract Early lymphocyte recovery (ELC) is associated with improved outcomes of hematologic malignancies after autologous hematopoietic stem cell transplantation (auto-SCT). ELC, its composition and impact on outcome depends on many variables; however there is limited data on ELC after different mobilization strategies (G-CSF [G] vs. G + high dose cyclophosphamide [GC] vs. G + plerixafor [GP]). Results from a recent study showed that GP based mobilization can affect the number and subsets of immune competent cells contained in the graft. We studied whether these differences are associated with immune reconstitution (ELC), engraftment, or long-term outcomes. We retrospectively identified patients undergoing auto-SCT at the Nashville VA Transplant Center between January 2000 and December 2010 in our CIBMTR database. Disease response was determined by standard CIBMTR response criteria. At our center, GP mobilization is reserved for patients who failed prior mobilization, to rescue G or GC mobilization, or as upfront usage in heavily pre-treated patients. Our patient cohort primarily included patients with multiple myeloma (MM) and lymphoma (LY). We had evaluable data on 333 patients (MM=196; LY=127; others=10). Comparative analysis of different mobilization methods are summarized in Table 1. Median number of regimens pre-SCT for MM was 2 (range 1-5) and for lymphoma 2 (range1-7). Among LY patients, 60 (47.3%) patients were in complete remission (CR), 58 (45.7%) in partial remission (PR) and 9 (7%) had stable disease (SD). Among MM patients, 69 (35.2%) were in CR or very good partial remission (VGPR) pre-transplant, 105 (53.5%) were in PR, and 14 (7.1%) had SD. There was no significant difference between disease response status among different mobilization methods for either the MM or LY patients. A higher absolute WBC count was seen in grafts after GP mobilization compared to G or GC (p=0.01), despite a majority of patients having received GP mobilization after failed G or GC mobilization, or as a rescue regimen (n=20 [89%]). Similarly, absolute lymphocyte counts were higher in grafts mobilized after GP compared to G or GC (p=0.01). All patients engrafted and there was no difference in time to WBC or platelet engraftment between mobilization methods. Although the GP cohort was more heavily treated than the other cohorts (>2 regimens for GP 82%, vs. G 72% vs. GC 58% [p=0.02]), progression-free survival (PFS) and overall survival (OS) of G vs. GC vs. GP at 2-years was not significantly different between MM and LY cohorts (Table 1). In summary, grafts mobilized with GP exhibited major differences in graft composition in conjunction with favorable post- transplant outcomes compared with grafts mobilized with G or GC. GP mobilization accelerated lymphocyte engraftment in this heavily treated group compared to G or GC. For patients proceeding to transplant heavily pre-treated, GP is a better mobilization method to ensure a robust graft is collected while avoiding the need for multiple stem cell collections and providing similar outcomes as patients less heavily treated and mobilized by G or GC. A prospective randomized controlled trial would elucidate whether progression free survival and overall survival might be improved by utilizing GP mobilization as a first-line therapy rather than as a rescue method. Table 1. Graft composition and outcomes of different stem cell mobilization methods Variable G (n=97) GC (n=213) GP (n=23) P value Numbers of regimens pre-SCT, median 2.2 (95% CI, 2.0-2.4) 1.9 (1.8-2.0) 2.3 (1.9-2.7) 0.02 WBC in graft, median (range) 184.8 (12-777.7) 138.6 (11-542) 286.1 (186-400.3) 0.01 Absolute lymphocyte in graft (x103), median (range) 128.1 (13-321.1) 73.9 (3.4-433.6) 161.2 (47.4-302.0) 0.01 ANC >500 (days), median (range) 16 (11-25) 15 (7-86) 18 (13-24) 0.16 Platelets >20 (days), median (range) 13 (9-22) 12 (7-18) 12 (10-21) 0.07 OS (2 year) Lymphoma 74.5 77.9 72.7 0.054 Multiple myeloma 89.6 74.4 72 0.76 PFS (2 year) Lymphoma 58.2 57.6 46.1 0.1 Multiple myeloma 66.3 49 60 0.21 Disclosures No relevant conflicts of interest to declare.

Download Full-text

Reduced intensity allogeneic stem cell transplantation in patients with myelodysplastic syndrome: Does the conditioning matter? A retrospective study of the SFGM-TC on 61 patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.6547 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 6547-6547

Author(s):

L. Terriou ◽

Z. Chir ◽

H. Esperou ◽

J. Boiron ◽

N. Gratecos ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Myelodysplastic Syndrome ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Chronic Gvhd ◽

Immunosuppressive Treatment ◽

Conditioning Regimen ◽

The Impact ◽

Reduced Intensity

6547 Background: Reduced-intensity allogeneic stem cell transplantation (RIT) has emerged as an alternative to myeloablative transplantation in pts with myelodysplastic syndrome (MDS). Given the uncertainty regarding the appropriate conditioning, SFGM-TC conducted a retrospective multicenter study with the attempt to evaluate the impact of conditioning on pts’ outcome. Methods: The record of 61 pts (37 males) with MDS who received a RIT between 1998 and 2003, from 22 French transplantation centres, were reviewed. According to the FAB classification, 11 pts had RA at diagnosis, of whom one had progressed to REAB and one to AML before transplantation. Thirty-two pts had REAB, of whom 2 had progressed to REAB-T and 7 to AML. Twelve pts had REAB-T and 6 CMML, of whom 8 progressed to AML. The median time from diagnosis to RIT was 12 months (6–129). Conditioning regimen consisted of fludarabin (Flu) plus busulfan ( n=29), Flu plus 2-Gy TBI ( n=20) and idarubicin plus aracytine and Flu (n=12). Donors were HLA-identical siblings (n=52) and HLA-matched unrelated (n=9). All pts received peripheral blood stem cells. The median of CD34+ infused cell dose was 5 × 106/kg (0.5–17.3). Results: At the reference date of 1 July 2005, median follow-up was 44.7 months (21–85). Estimated 3-year overall survival (OS), progression free survival (PFS), relapse and transplant-relapse mortality (TRM) were 35%, 27%, 66% and 30%, respectively. Neither of the 3 conditioning regimens used had impact on pts’ outcome. In multivariable analyses, while acute III/IV grade GVHD development was the only factor found to adversely influencing OS (HR=3.6; 95% CI: 1.1–12.2), chronic GVHD development was the only favourably influencing PFS and relapse ratios (HR=0.3; 95% CI: 0.1–0.7 and HR=0.2; 95% CI: 0.1–0.6, respectively). TRM was adversely influenced by male sex of pt (HR=9.2; 95% CI: 1.5–66.6). Conclusions: RIT seems to be an effective treatment in MDS pts irrespective of conditioning type. While acute III/IV grade GVHD appeared to be detrimental, the benefit effect of chronic GVHD was to be bound to GVL effect. New approaches with focus on immunosuppressive treatment are needed to enhance the GVL effect with an acceptable risk of GVHD. No significant financial relationships to disclose.

Download Full-text

The Survival of Multiple Myeloma Patients: A Single Institution Study.

Blood ◽

10.1182/blood.v104.11.5223.5223 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5223-5223

Author(s):

Zwi N. Berneman ◽

An-Sofie Verstraete ◽

Alain Gadisseur ◽

Ann Van de Velde ◽

Wilfried A. Schroyens

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Progression Free Survival ◽

High Dose Chemotherapy ◽

High Dose ◽

Conventional Chemotherapy ◽

Free Survival

Abstract Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients. Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated. Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p < 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020). Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).

Download Full-text

Updated Outcomes and Impact of Age With Lenalidomide and Low-Dose Dexamethasone or Melphalan, Prednisone, and Thalidomide in the Randomized, Phase III FIRST Trial

Journal of Clinical Oncology ◽

10.1200/jco.2016.66.7295 ◽

2016 ◽

Vol 34 (30) ◽

pp. 3609-3617 ◽

Cited By ~ 49

Author(s):

Cyrille Hulin ◽

Andrew Belch ◽

Chaim Shustik ◽

Maria Teresa Petrucci ◽

Ulrich Dührsen ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Low Dose ◽

Progression Free Survival ◽

Disease Stage ◽

Newly Diagnosed ◽

Free Survival ◽

One To One

Purpose This analysis of the FIRST trial in patients with newly diagnosed multiple myeloma (MM) ineligible for stem-cell transplantation examined updated outcomes and impact of patient age. Patients and Methods Patients with untreated symptomatic MM were randomly assigned at a one-to-one-to-one ratio to lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks), stratified by age (≤ 75 v > 75 years), disease stage (International Staging System stage I/II v III), and country. The primary end point was progression-free survival. Rd continuous and MPT were primary comparators. Results Between August 21, 2008, and March 7, 2011, 1,623 patients were enrolled (Rd continuous, n = 535; Rd18, n = 541; MPT, n = 547), including 567 (35%) age older than 75 years. Higher rates of advanced-stage disease and renal impairment were observed in patients older than 75 versus 75 years of age or younger. Rd continuous reduced the risk of progression or death compared with MPT by 31% (hazard ratio [HR], 0.69; 95% CI, 0.59 to 0.80; P < .001) overall, 36% (HR, 0.64; 95% CI, 0.53 to 0.77; P < .001) in patients age 75 years or younger, and 20% (HR, 0.80; 95% CI, 0.62 to 1.03; P = .084) in those age older than 75 years. Median overall survival was longer with Rd continuous than with MPT, including a 14-month difference in patients age older than 75 years. Progression-free survival with Rd18 was similar to that with MPT, and overall survival with Rd18 was marginally inferior to that with Rd continuous. Rates of grade 3 to 4 treatment-emergent adverse events were similar for Rd continuous–treated patients age 75 years or older and those age older than 75 years; however, older patients had more frequent lenalidomide dose reductions. Conclusion Results support Rd continuous treatment as a new standard of care for stem-cell transplantation–ineligible patients with newly diagnosed MM of all ages.

Download Full-text