scholarly journals 361: Superior disease-free survival in acute myelogenous leukemia/myelodysplastic syndrome receiving reduced-intensity allogeneic hematopoietic stem cell transplantation from unrelated donors using fludarabine, busulfan, and total lymphoid irradiation

2007 ◽  
Vol 13 (2) ◽  
pp. 131 ◽  
Author(s):  
K. Kato ◽  
Y. Khaled ◽  
T. Braun ◽  
J.E. Levine ◽  
J.L.M. Ferrara ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Total Lymphoid Irradiation ◽  
Acute Myelogenous ◽  
Unrelated Donors ◽  
Disease Free ◽  
Reduced Intensity

Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients - A Single Center Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3030-3030
Author(s):  
Michael Stadler ◽  
Bernd Hertenstein ◽  
Juergen Krauter ◽  
Stefanie Buchholz ◽  
Elke Dammann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic cell transplantation (alloHSCT) has curative potential in many hematologic malignancies; however, substantial treatment related toxicity has restricted its use to younger patients (mostly under 55 years of age). With the development of conditioning regimens of reduced intensity, alloHSCT is being applied more widely in elderly patients, too. Here we report the results of all consecutive alloHSCT recipients above the age of 55 years transplanted at our institution between October 1996 and April 2006. Among 89 elderly patients transplanted, 50 patients were in the age group over 55 to 60 years, 31 patients in the cohort over 60 to 65 years, and 8 patients were older than 65 years. 36 patients were female and 53 male. Diagnoses included acute lymphoblastic leukemia (ALL, 10 patients), acute myelogenous leukemia (AML, 32), myelodysplastic syndromes (MDS) or secondary AML (30), chronic myelogenous leukemia (CML, 5), agnogenic myeloid metaplasia (AMM, 3), lymphoma (5), and multiple myeloma (4 patients). Advanced disease was present in 63 patients (71%) at the time of transplant. 85 patients (96%) had a WHO performance score of 0 or 1. Conditioning regimen was myeloablative in 20 patients (22%) and of reduced intensity in 69 patients (78%); in 46 patients (52%) irradiation was part of the conditioning regimen. Stem cell source was peripheral blood in 83 patients (93%) and bone marrow in 6 (7%). 32 patients (36%) received a graft from a related donor and 57 (64%) from an unrelated donor. After a median follow-up of 9 months (range: 1 to 104), 24 patients have since relapsed (27%). Treament related mortality was 27% (24 of 89 patients). 34 patients developed acute graft-versus-host disease (GvHD, 38%) and chronic GvHD was diagnosed in 25 of 71 patients at risk (35%). As of August 1st, 2006, 47 of 89 patients were alive and 41 of 89 in complete remission. Probabilities of overall and disease-free survival at three years were 45 and 32%, respectively. Interestingly, overall and disease-free survival were similar among the three age cohorts. In conclusion, according to our experience, alloHSCT is feasible in elderly patients of appropriate performance status, with acceptable relapse rates and toxicity. Figure Probability of overall survival in elderly patients after alloHSTC Figure Probability of overall survival in elderly patients after alloHSTC

Improved Outcomes for Peripheral Blood Stem Cell Transplantation in Advanced Myelodysplastic Syndrome.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2304-2304
Author(s):  
Scott R. Solomon ◽  
Richard Childs ◽  
Aldemar Montero ◽  
Elaine Sloand ◽  
Laura Wisch ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Advanced Disease ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Blood Stem Cell Transplantation ◽  
Reduced Intensity ◽  
Risk Of Relapse ◽  
Related Mortality

Abstract Allogeneic marrow or peripheral blood stem cell transplantation (PBSCT) is the only curative treatment for myelodysplastic syndrome (MDS). Historically, transplantation for MDS has produced long-term disease-free survival rates of 30–40%, partially due to high procedural mortality (~40%) in this patient population. Although transplant outcomes in younger patients with low-risk disease have been favorable, inferior results are seen in older patients and those with more advanced disease. Evidence suggests that the lower transplant-related mortality (TRM) and improved graft-versus-leukemia seen with PBSCT may translate into improved clinical outcomes for MDS patients. Forty-four patients, aged 12–73 years (median 50) received a PBSCT from a matched related sibling donor (MRD). Patients aged <55 years, without prohibitive comorbidity, received myeloablative conditioning consisting of total body irradiation and cyclophosphamide, followed by a T cell depleted allograft and scheduled post-transplant donor lymphocyte infusions (MST, n=23). Patients ineligible for an ablative transplant due to age or poor health received reduced intensity conditioning (fludarabine and cyclophosphamide, melphalan, or busulfan) followed by a T cell replete allograft (n=21). Six patients had low-risk MDS (RA/RARS), while the majority of patients (86%) had advanced disease (RAEB [9], RAEBT [6], AML [13], therapy-related MDS [10]). Median follow-up is 15.3 (range 2–82) months. Patients with therapy-related MDS had a significantly lower survival rate due to a very high risk of relapse (figure). The actuarial probabilities of overall survival (OS), disease-free survival (DFS), relapse, and TRM were 64%, 59%, 26%, and 23% for primary MDS patients, and 51%, 47%, 40%, and 25% for the whole cohort. Transplant-related mortality in patients under 50 years of age was 11% vs. 45% in patients ≥50 years (p=0.03). OS and DFS were significantly better in recipients of MST (64%, 57%) than in patients receiving reduced-intensity PBSCT (33%, 34%), due to a higher risk of relapse in the latter group (55% vs. 29%, p=0.10). In nineteen patients <50 years receiving MST, actuarial probability of OS, DFS, relapse, and TRM were 81%, 72%, 23%, and 7%, respectively. In summary, PBSCT yields superior outcomes for patients with primary MDS, even in patients in transformation to AML. The inferior outcomes seen in therapy-related MDS suggest alternative therapies are required for this patient population. Reduced intensity transplantation permits curative therapy for MDS patients not amenable to MST, but at the price of increased TRM and relapse in this older cohort. Figure Figure

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.

Disease-Free Survival Of Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation Is Not Associated With Disease Status and Donor Sources

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2158-2158
Author(s):  
Yue Lu ◽  
Tong Wu ◽  
Xing-Yu Cao ◽  
Yan-Li Zhao ◽  
De-Yan Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Disease Status ◽  
Refractory Anemia ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Disease Free ◽  
Related Mortality

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is an only curative modality currently for myelodysplastic syndrome (MDS). High-risk MDS usually has lower complete remission (CR) rate and higher chemotherapy-related mortality compared with de novo acute myeloid leukemia (AML). To examine whether CR before HSCT has survival benefit for MDS treated by HSCT, we retrospectively analyzed the data during 11 years from our center. The clinical outcomes of MDS after HSCT from different donor sources have also been evaluated. Objective In present clinical study, the effects of disease status and donor sources on disease-free survival (DFS) of MDS after HSCT were studied. Methods From August 2001 to December 2012, total 122 patients with MDS that underwent HSCT in our center were enrolled. Male to Female was 76: 46. The median age was 35 (8 to 57) years old. The median blasts in bone marrow (BM) before conditioning were 9% (1% to 65%). According to 2008 WHO classification, the patients were diagnosed as refractory cytopenias with unilineage dysplasia (RCUD) in 12, refractory anemia with ring sideroblasts (RARS) in 2, 5q- in 1, refractory cytopenias with multilineage dysplasia (RCMD) in 15, refractory anemia with excess blasts (RAEB) -1/RAEB-2 in 36 and transformed AML in 56. For International Prognostic Scoring System (IPSS), 12 patients were in low-risk, 27 in intermediate-1, 24 in intermediate-2, and 59 in high-risk. Based on BM blast percentage pre-conditioning, 47 cases were less than 5%, 43 patients were between 5% to 20%, and 32 cases were more than 20%. The stem cells were from identical siblings (45) or unrelated donor (24) or haploidentical family members (53). Conditioning regimens were BUCY/BUFLU for identical sibling HSCT, and BUCY/BUFLU plus ATG (Thymoglobuline, 8-10mg/kg) for unrelated or haploidentical transplants. Graft-versus-host disease prophylaxis was employed by Cyclosporin A, Methotrexate and Mycophenolate mofetil as reported previously (DP Lu et al., Blood 2006; 107:3065). Results: With median follow-up 31 (1-144) months, DFS was 73.8%. Fourteen patients (11.4%) relapsed. Transplant-related mortality was 14.8%. No significant differences on DFS were found among RCUD/RARS/5q- (68.8%), RCMD (85.7%), RAEB-1/RAEB-2 (72.2%) and transformed AML (73.2%) (p=0.761). A similar DFS was seen in different risk categories (73.3% in low-risk, 79.2% in intermediate-1, 75.0% in intermediate-2 and 71.2% in high-risk; p=0.861). Moreover, CR or not before HSCT has no remarkable effect on DFS (blasts <5%, 78.7%; blasts 5% to 20%, 67.4%; blasts > 20%, 75.0%; p=0.342). Donor sources have also no significant effects on DFS (identical sibling 75.6%, unrelated donor 79.2%, haploidentical family member 69.8%; p=0.651). Conclusions Our clinical results have shown that under current protocol, DFS of MDS after allogeneic HSCT is quite encouraging no matter the disease status and stem cell donor sources. Therefore, it is not necessary that complete remission is achieved by chemotherapy before transplant. Haploidentical family member is an important alternative donor for patients with MDS when matched either identical sibling or unrelated donor is not available. Disclosures: No relevant conflicts of interest to declare.

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