Hematopoietic Stem Cell Transplantation after Reduced Intensity Conditioning in Acute Myeloid Leukemia Patients Older Than 40 Years.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5074-5074
Author(s):  
Cynthia Huisman ◽  
Ellen Meijer ◽  
Eefke J. Petersen ◽  
Henk M. Lokhorst ◽  
Leo F. Verdonck
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free

Abstract Reduced intensity conditioning (RIC) protocols are increasingly used for allogeneic hematopoietic stem cell transplantation (HSCT) in elderly patients. We retrospectively analyzed the outcome of RIC HSCT in a homogeneous group of acute myeloid leukemia (AML) patients over the age of 40. Forty-three AML or high-risk myelodysplastic syndrome patients were treated with a fludarabine and low dose total body irradiation (TBI) based regimen, followed by a full peripheral stem cell graft. Antithymocyte globulin was given to matched unrelated recipients (34%) before infusion of fludarabine. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin and mycophenolate mofetil. All but 2 AML patients were in complete remission at the time of transplantation. Seventy-six percent of patients had a poor risk profile. Hematologic recovery was fast and primary graft failure occurred in one patient. Two patients with active disease at the time of HSCT experienced ongoing relapse. Infections were diagnosed in 9 patients (21%) and 6 patients (14%) were treated for CMV reactivation. Sixty percent of patients developed acute GVHD, which was grade 2 in 40% and grade 3 in 12%. Chronic GVHD occurred in 33% of patients. The incidence and severity of both acute and chronic GVHD was similar in patients with related and unrelated donors (P = 0.84 and 0.74, respectively). Treatment-related mortality (TRM) was low (9%), total nonrelapse mortality was 19%. After a median follow-up of 571 days, 16 patients (37%) experienced relapse. One-year progression-free and overall survival were 61% and 67%, respectively. Median disease-free survival has not been reached yet (> 58 months) and median overall survival was 31 months (Fig 1 and 2, respectively). Poor risk AML was significantly associated with disease-free survival in multivariate analysis (P = 0.02). Age > 60 years, gender, donor type, timing of RIC HSCT (upfront or after relapse) and acute GVHD were not identified as prognostic factors. In conclusion, fludarabine plus low-dose TBI-based RIC HSCT is effective in AML patients over the age of 40 without active disease at the time of transplant and is associated with low TRM. Figure Figure Figure Figure

Risk Factors for Graft-versus-Host Disease (GVHD) Following Myeloablative HLA-Identical Sibling Transplantation with Allogeneic Peripheral Blood Stem Cells (PBSC): An Analysis of 546 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3318-3318
Author(s):  
Mohamad Mohty ◽  
Keyword(s):  
Risk Factors ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Individual Patient Data ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Factors Associated ◽  
Disease Free

G-CSF-mobilized PBSCs are increasingly used in allogeneic transplantation. In comparison to bone marrow (BM), PBSCs have been shown to allow faster engraftment, but also can lead to more chronic GVHD. Our current knowledge of risk factors for GVHD is based primarily on historical analyses performed using BM as the stem cell source. This analysis sought to identify potential risk factors predicting for the development of acute and chronic GVHD after related HLA-identical PBSC transplantation (PBSCT). We analyzed the outcome of 546 patients who were part of an international database bringing together individual-patient data from nine randomized trials. Median age of recipients was 39 years. 180 (33%) patients had acute myeloid leukemia (AML), 237 (43%) had chronic myeloid leukemia (CML) and 129 patients had other hematological malignancies. 398 (73%) patients had standard risk disease at time of PBSCT and 218 (41%) patients received TBI-based myeloablative conditioning. 312 (57%) patients received short-course methotrexate (days 1, 3, 6) as GVHD prophylaxis, while 234 (43%) received long-course methotrexate (days 1, 3, 6, 11). 190 (35%) patients received G-CSF post-transplant. An ANC of >500/μL was reached at a median of 16 (range, 8–50) days. Platelet recovery occurred at a median of 15 (range, 5–376) days. The incidence of grades II-IV acute GVHD was 44% (95%CI, 40–48%), while the incidence of extensive chronic GVHD was 40% (95%CI, 36%–44%). In a Cox multivariate analysis, the incidence of acute GVHD was significantly associated with age (P=0.001; RR=1.60 for age >40; 95%CI, 1.2–2.1), and TBI-based conditioning (P=0.0009; RR=1.7; 95%CI, 1.2–2.2). The main risk factors associated with an increased risk of extensive chronic GVHD in a Cox multivariate analysis were grade II-IV acute GVHD and a female donor (P=0.009; RR=1.5; 95%CI, 1.1–2.0; and P<0.0001; RR=2.2; 95%CI, 1.6–2.9 respectively). At a median follow-up of 35 months, disease-free survival (DFS) was significantly higher in patients with extensive chronic GVHD compared to patients without extensive chronic GVHD (P=0.03). G-CSF post-transplant (P=0.0027; RR=1.9; 95%CI, 1.2–2.9), disease status at transplant ((P<0.0001; RR=2.9 for advanced diseases; 95%CI, 1.9–4.3), and a diagnosis of acute leukemia (AML or ALL; P<0.0001; RR=3.5; 95%CI, 2.2–5.6) were the major factors associated with worsened disease-free-survival. In conclusion, although the use of PBSCs is associated with more frequent and clinically more severe chronic GVHD, this large-scale analysis based on individual-patient data demonstrates that some risk factors for GVHD after PBSCT are qualitatively comparable to those observed with BM-derived stem cells and might be determinant for the ultimate outcome. Most importantly, extensive chronic GVHD is associated with significantly improved DFS, while the use of G-CSF post-transplant might be detrimental.

Allogeneic Stem Cell Transplantation In Chronic Myeloid Leukemia In TKIs Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5554-5554
Author(s):  
Parvez Ahmed ◽  
Syed Karman Mahmood ◽  
Tariq Mahmood Satti ◽  
Qamar Un Nisa Chaudhry ◽  
Nighat Shahbaz ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Treatment Option ◽  
Myeloid Leukemia ◽  
Cox Regression ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Free Survival ◽  
Standard Risk ◽  
Disease Free

Abstract Introduction Tyrosine kinase inhibitors (TKIs) have largely replaced allogeneic hematopoietic stem cell transplantation (HSCT) as first line treatment option in chronic phase chronic myeloid leukemia (CML) yet due to the need for continued administration the cost becomes prohibitive in majority of patients without any health insurance coverage. Therefore allogeneic stem cell transplant remains a reasonable treatment option for such patients especially in resource constrained countries. It is also useful treatment modality in children, CML in accelerated phase and in patients intolerant to TKIs. We report results of 64 consecutive patients undergoing HLA matched sibling allo HSCT at our center from April 2002 to September 2012. Methods Patients with Philadelphia positive CML were categorized into standard and high risk based on age >40 years, disease duration > 12 month from diagnosis to transplant and accelerated phase. Conditioning regimens used were oral busulphan 16 mg/kg plus cyclophosphamide 200 mg/kg (Bu16/Cy200), Bu16/Cy120, Bu16/Cy120/Etoposide30 and Bu16/Cy120/ATG. Source of stem cell was peripheral blood stem cells (PBSC) or bone marrow (BM) infusion. GVHD prophylaxis consisted of ciclosporin, short methotrexate (10 mg/m2 on day +1, 8 mg/m2 on day +3 & 6) ± prednisolone. Statistical calculations included Fisher’s exact test, Kaplan-Meier for survival analysis, and Cox regression for multivariate analysis. Results Median age of the patients was 28 years (range 7 – 54). Female donor to male recipient was seen in 12 cases while 20 patients had major blood group mismatch. Forty seven patients were standard risk while 17 were categorized as high risk. Bu16/Cy120 was the most common conditioning regimen given in 34 cases followed by Bu16/Cy200 in 19 cases. Fifty four patients received PBSC while BM was given in 8 cases. Grade I/II acute GVHD was seen in one-third of the cases while 7 (11%) had grade III/IV GVHD. Extensive chronic GVHD was seen in 10 (16%) cases while 12 (19%) patients had limited chronic GVHD. Complications observed were hemorrhagic cystitis (7), VOD (4), CMV infection (2) and septicemia (3). Five (8%) patients had disease relapse. The overall survival was 70.3% (median 1627 days) while disease free survival was 62.5% (median 1547 days). Nineteen patients died of various complications like extensive GVHD (n=5), septicemia (n=3), VOD (n=3), CMV infection (n=3) and disseminated aspergillosis (n==2). A significant difference was observed among patients bearing standard risk compared with those in high risk group in terms of overall survival (79% versus 47% , p=0.013), disease free survival (72% versus 35%, p=0.031) and incidence of acute GVHD (34% versus 71%, p=0.01) in univariate analysis. Age >40 year was the only factor associated with adverse outcome in multivariate Cox-regression model. Conclusions Early allogeneic HSCT in CML patients <40 years of age is associated with long term disease free survival in about 70% of cases. It is a reasonable treatment option in situations where TKIs cannot be employed as first line therapy due to various reasons. Disclosures: No relevant conflicts of interest to declare.

HLA DR15 Antigen Status Does Not Impact Graft-Versus-Host Disease or Disease-Free Survival in HLA-Matched Sibling Transplantation for Hematologic Malignancies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3094-3094
Author(s):  
Minoo Battiwalla ◽  
Kristin Ellis ◽  
Steven Z. Pavletic ◽  
Gorgun Akpek ◽  
Peiman Hematti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Graft Versus Host ◽  
Matched Sibling ◽  
Disease Free

Abstract Abstract 3094 The HLA class II DRB1 antigen DR15 is an important immunobiologic marker in immune mediated marrow failure states. DR15 has also been reported in small studies to be associated with favorable outcomes (reduction in acute GVHD and reduced relapse resulting in improved overall survival) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on major transplant outcomes, we conducted a retrospective study of 2, 891 recipients of first marrow or mobilized peripheral blood stem cell transplantation for the treatment of acute myeloid leukemia (n=1038), acute lymphoblastic leukemia (n=700), chronic myeloid leukemia (n=948), or myelodysplastic syndrome (n=205) between 1990–2008 and reported to the CIBMTR registry. Selection was confined to HLA-identical sibling transplantation to avoid HLA-disparity as a driving force for observed differences. All patients received conventional myeloablative conditioning, T-replete grafts and cyclosporine plus methotrexate- based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 (25.3%) patients as positive and 2159 (74.7%) patients as negative for DRB1*15 :01 or *15 :02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15-positive and -negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, acute graft-versus-host disease (GvHD) II-IV or III-IV, chronic GVHD, treatment related mortality, relapse, disease-free survival or overall survival. Confining the univariate analysis to myeloid malignancies did not alter these findings. Multivariate analysis models were constructed with DR15 status forced into the models in all steps of model building and the final model regardless of its statistical significance. Other variables tested included: donor/recipient age, CMV status, disease, disease stage, graft source, Karnofsky score, race and year of transplant. Variables that attained a p-value ≤0.05 were held in the final multivariate models. In multivariate analysis, DR15 status showed no significant difference in the primary outcomes of acute GVHD II-IV or III-IV, chronic GVHD, overall survival, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplantation outcomes in this large and homogenous cohort of leukemia and MDS patients. Disclosures: No relevant conflicts of interest to declare.

Predictable Prognostic Factor of CD56 Expression in Acute Myeloid Leukemia with t(8:21) Including Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3288-3288
Author(s):  
Deok-Hwan Yang ◽  
Yeung-Chul Mun ◽  
Ho-Jin Shin ◽  
Yeo-Kyeoung Kim ◽  
Je-Jung Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Cd56 Expression ◽  
Disease Free ◽  
Acute Myeloid

Abstract CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multi-drug resistance, but the clinical and prognostic significances are not yet clearly defined. Recently, some investigators reported that AML patients with t(8;21) showed more frequent CD56 expression rate and the expression of CD56 antigen adversely affected disease-free survival (DFS). It could explain a diverse clinical outcome in AML patients with favorable cytogenetics. This study investigated CD56 expression in 37 adult de novo AML patients with t(8:21) between November 1996 and June 2005 at three institutions. Immunophenotyping was performed with flow cytometry (Coulter EPICS XL) and considered positive if at least 20% of blasts expressed. CD56 was expressed in 25 cases (67.6%). There was no statistically significant differences in age, sex, leukocyte count, the percentage of bone marrow blasts or the presence of additional cytogenetic abnormalities between the CD56+ and the CD56- group. The complete remission (CR) rate to standard dose cytarabine or N4-behenoyl-1-D-arabinofuranosylcytosine (BH-AC) and idarubicin was similar in both groups (91.7% v 88.7%; P=0.73), but the relapse rate to high-dose cytarabine or allogeneic hematopoietic stem cell transplantation (HST) was quite different (60% v 25%; P=0.08). Allogeneic HST was performed from siblings in 15 patients (40.5%) who achieved CR, 8 patients (32.0%) in CD56+ and 7 patients (58.3%) in CD56- group (P=0.16). The median durations of DFS were significantly shorter in CD56+ (median, 12.2 months) than in the CD56- group (median, not reached) (P =0.02). Also, the median durations of survival showed the same results in the CD56+ group (median, 14.9 months) compared with the CD56- group (median, not reached) (P=0.01). Within fifteen transplanted patients, the median durations of DFS in eight CD56+ patients was significantly shorter than seven CD56- patients (median, 24.4 months v not reached; P=0.02)(Fig.1 and 2).We concluded that CD56 expression was associated with reduced DFS and survival for AML patients with t(8:21) including transplanted patients. Although further larger studies are needed, we suggested that CD56 expression at diagnosis is a predictable prognostic factor in AML with t(8:21). Fig. 1 Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 1. Disease-free survival (DFS) and Overall survival (OS) for patients with t(8:21) with CD56+ (n−25) and CD56− (n−12) group. Fig. 2 Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression. Fig. 2. Within transplanted patients, decreases from survival (DFS) for patients with t(8:21) with and without CD56 expression.

Graft-Versus-Host Disease (GVHD) Induced Graft-Versus-Leukemia (GVL) Effect: More Impact on Later Relapse and Disease-Free Survival Following Reduced Intensity Conditioning

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1014-1014
Author(s):  
Daniel J. Weisdorf ◽  
Mei-Jie Zhang ◽  
Mukta Arora ◽  
J. Douglas Rizzo ◽  
Mary M. Horowitz ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Treatment Failure ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Control Group ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract Abstract 1014 GVHD can induce non-relapse transplant-related mortality (TRM) and can augment the GVL effect after hematopoietic cell transplantation (HCT). The net impact on survival represents a balance of these parallel immunologic influences. We examined the effect of acute and/or chronic GVHD on risks of late (beyond 1 year) relapse, TRM and disease-free survival (DFS) after allogeneic HCT for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS); and probed any differential influences using either myeloablative (MA) or reduced intensity conditioning (RIC). Landmark analysis was performed at 1-year as all acute GVHD and over 95% of chronic GVHD had occurred within 1 year after HCT. Eligible patients had to be disease-free and alive at 1-year. Between 1997–2006, 5741 patients with AML/MDS received HCT; of these, 2369 patients survive disease-free at 1-year. Approximately 70% had AML and 30% MDS. Disease status at HCT for the study cohort (alive disease-free at 1-year), were 40% in first complete remission (CR), 17% in 2nd or later CR and 43% in relapse. MA conditioning recipients (70% of the cohort) had a median age of 42 years; RIC (30% of the cohort) median 56 years. For analysis we compared: 1) patients without acute or chronic GVHD [baseline control group; No], 2) acute GVHD only [Ac], 3) chronic GVHD only [Chr] and 4) both acute and chronic GVHD [Ac/Chr]. Following MA conditioning late relapse risks were not significantly different in the 4 groups: No GVHD (RR 1.0), Ac GVHD only (RR 0.96, p=0.87), Chr GVHD only (RR 1.01, p=0.94) and Ac/Chr GVHD (RR 0.96, p=0.81) (Figure 1). In contrast, TRM risks were higher with any GVHD; Ac GVHD only (RR 2.31, p=0.004), Chr GVHD only (RR 3.43, p<0.0001) and Ac/Chr GVHD (RR 4.50, p<0.0001). Consequently, after MA HCT, treatment failure (TRM or relapse) was similar with Ac GVHD only (RR 1.32, p=0.13) compared to those with No GVHD, but was significantly higher with either Chr GVHD only (RR 1.62, p=0.0002) or Ac/Chr GVHD (RR 1.85, p<0.0001). Following RIC regimens, relapse risks were similar with no GVHD (RR 1.0), Ac GVHD only (RR 0.70, p=0.37) and Chr GVHD only (RR 0.72, p=0.22), but relapse was significantly lower in patients Ac/Chr GVHD (RR 0.49, p=0.02) (Figure 2). TRM was similar with No GVHD, Ac GVHD only (RR 1.25, p=0.63) and Chr GVHD only (RR 1.36, p=0.36), but TRM was higher in patients with Ac/Chr GVHD (RR 2.69, p=0.002). Consequently, treatment failure was similar in all groups: No GVHD (RR 1.0), Ac GVHD only (RR 0.88, p=0.67), Chr GVHD only (RR 0.93, p=0.73) and Ac/Chr GVHD (RR 1.22, p=0.32) (Figure 3). These data suggest that when using MA conditioning either Ac and/or Chr GVHD has an adverse effect on TRM without compensatory augmentation of GVHD-associated GVL, thus leading to worse DFS. MA HCT must use better strategies to prevent any GVHD. However, using RIC regimens, Ac plus Chr GVHD limits risks of relapse, but without adverse effect on survival and disease-free survival. Therefore, following RIC HCT, GVHD-associated GVL may be more important in limiting late leukemia recurrence. Overly suppressive approaches to eliminate any GVHD might increase relapse risks after RIC HCT for AML and MDS. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem-Cell Transplantation Using a Reduced-Intensity Conditioning Regimen Has the Capacity to Produce Durable Remissions and Long-Term Disease-Free Survival in Patients With High-Risk Acute Myeloid Leukemia and Myelodysplasia

2005 ◽  
Vol 23 (36) ◽  
pp. 9387-9393 ◽  
Author(s):  
Sudhir Tauro ◽  
Charles Craddock ◽  
Karl Peggs ◽  
Gulnaz Begum ◽  
Premini Mahendra ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Purpose The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. Patients and Methods Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). Results The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. Conclusion The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.

Improved Disease Survival without Increased GVHD Using Low Dose Cyclosporine and Prednisone in Allogeneic Stem Cell Transplantation - a Case Control Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5148-5148
Author(s):  
John J. Moore ◽  
David D. Ma ◽  
Tony Dodds ◽  
Sam Milliken ◽  
Keith Fay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Survival Benefit ◽  
Low Dose ◽  
Disease Free Survival ◽  
Prophylactic Regimen ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Disease Free

Abstract Allogeneic stem cell transplantation (HSCT) can cure numerous malignant and non-malignant diseases but this is offset by significant morbidity and mortality from graft versus host disease (GVHD). The standard prophylactic regimen contains cyclosporine, methotrexate and/or prednisone however doses and the timing of tapering remain unclear. Recently Ruutu et al demonstrated reduced GVHD using a prednisone based prophylactic regimen without a survival benefit whereas Baclgalupo et al demonstrated an increased survival benefit with 1mg/kg cyclosporine over 3mg/kg which strongly correlated with cyclosporine levels. Since early 2002 we have adopted both these strategies in an attempt to reduce GVHD in myeloblative HSCT but still maintain disease free survival. Consecutive myeloblative allogeneic HSCT patients (n=47, median age 41 yrs, 28 sibling or family, 19 unrelated) underwent HSCT using cyclosporine 1mg/kg, standard dose methotrexate and prednisone commencing at D14 0.5mg/kg, according to Ruutu et al. All sibling allograft patients underwent conditioning with Bu/Cy whereas unrelated recipients received Cy/TBI. This group was compared with 94 historical controls for age and disease status (median age 36 yrs, 63 sibling or family, 31 unrelated). At a median of 1 year follow up (range 100–600 days), overall and disease free survival is significantly increased in the low dose cyclosporine/prednisone arm (OS: 75% vs 50% at 1 yr, p=0.04). Acute GVHD (II–IV) was similar in both arms at D100 with a trend to less GVHD in the low dose cyclosporine/prednisone arm (20% vs 30%, p=0.1). These results suggest that the low dose cyclosporine/prednisone regimen has controlled GVHD whilst maintaining an adequate GVL effect. Randomised trials using this regimen may be warranted to fully determine its place in allogeneic HSCT prophylaxis.

Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning (RIC) Regimen Has the Capacity To Produce Durable Remissions and Long Term Disease-Free Survival in Patients with High Risk Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1141-1141
Author(s):  
S. Tauro ◽  
S. Mackinnon ◽  
K. Peggs ◽  
G. Begum ◽  
P. Mahendra ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract The toxicity of allogeneic stem cell transplantation (SCT) can be substantially reduced by the use of a reduced intensity conditioning (RIC) regimen and this has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with AML and MDS has not yet been defined and consequently their role in the management of these diseases remains conjectural. Seventy-six patients with high risk AML or MDS were allografted using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range 18–71 years). There were 46 males and 30 females; 41 patients received an allograft from an unrelated donor and 35 from a matched sibling donor. The 100 day transplant related mortality was 9% and no patient developed greater than Grade 2 graft-versus-host disease (GVHD). With a median follow-up of 36 months (range 13–70 months) 27 patients were alive and in remission with a 3y actuarial overall survival (OS) and disease-free survival (DFS) rate of 41% and 37% respectively. The 3y OS and DFS of patients with AML in complete remission (CR) at the time of transplantation was 48% and 42% respectively. In a multivariate setting, Cox regression analysis demonstrated prognostic significance of disease stage at the time of transplant with improved DFS in patients with AML in CR at the time of transplantation (HR=2.03, 95% CI=1.02–4.07). Disease relapse was the commonest cause of treatment failure occurring at a median time of 6 months post-transplant. Fourteen out of 27 (52%) patients relapsed within 6 months and 23/27 (85%) within twelve months defining a relatively narrow window for therapeutic intervention to prevent disease recurrence. The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts are capable of producing sustained disease free survival in a significant number of patients with AML who would be ineligible for allogeneic transplantation using a myeloablative conditioning regimen.

Clinical Research of Autologous Hematopoietic Stem Cell Transplantation for Hematological Malignancies and Solid Tumors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5475-5475
Author(s):  
Zhen-qian Huang ◽  
Dong-hua Zhang ◽  
Huo Tan ◽  
Cheng-zhi Zhou ◽  
Dan Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Malignant Lymphoma ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free

Abstract Objective: To evaluate the therapeutic effect of autologous hematopoietic stem cell transplantation (AHSCT) on hematological malignancies and solid tumors. Methods: 20 patients with median age of 33.4±11.3 (18–50) years received AHSCT, 7 of them were acute non-lymphoblastic leukemias (ANLL)(CR1 5, CR2 1, refractory/relapse 1), 2 were acute lymphoblastic leukemia (ALL)(CR1 2), 1 was chronic myelogenous leukemia (CML-CP2), 1 was chronic lymphoblastic leukemia(CLL-NR), 6 were malignant lymphoma (CR1 2, CR2 2, NR 2), 1 was multiple myeloma, 1 was breast cancer relapsed after resection 10 years and lung and bone metastases, 1 was small cell lung cancer. 2 or 3 of following agents: Cytarabine(Ara-C)3–4g/m2, Cyclophosphamide (CTX) 4–6g/m2, Etoposide (VP-16) 0.5–1.0g/m2, Semustine (me-CCNU) 300mg/m2, Melphala n(Mel) 140mg/m2, Thiotep a (TSPA) 600mg/m2, Carboplatin (CBP) 1.0g/m2, were combined as conditioning regimen in all patients. Among them 2 patients with ALL accepted additional total body irradiation (TBI). Results: All the patients have reconstituted bone marrow hematopoiesis after transplantation. None of them had the transplantation-related mortality. Among 20 cases, 15 achieved disease free survival (DFS) follow-up 36.5(2–106) months. Conclusion: AHSCT might represent an effective approach for the treatment of some patients with chemosensitive solid tumor who are complete remission or part remission. Without compatible donors, patients with leukemia and malignant lymphoma at CR1 stage could receive AHSCT to reduce relapse and increase disease-free survival. It is suggest that have a obvious survival benefit from AHSCT.

Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5054-5054
Author(s):  
Amir Peyman ◽  
Stephen Couban ◽  
Kara Thompson ◽  
Louis Fernandez ◽  
Donna L. Forrest ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

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