Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3456-3462 ◽  
Author(s):  
Partow Kebriaei ◽  
Michelle A. Detry ◽  
Sergio Giralt ◽  
Antonio Carrasco-Yalan ◽  
Athanasios Anagnostopoulos ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic stem-cell transplantation (HSCT) remains an effective strategy for inducing durable remission in chronic myeloid leukemia (CML). Reduced-intensity conditioning (RIC) regimens extend HSCT to older patients and those with comorbidities who would otherwise not be suitable candidates for HSCT. The long-term efficacy of this approach is not established. We evaluated outcomes of 64 CML patients with advanced-phase disease (80% beyond first chronic phase), not eligible for myeloablative preparative regimens due to older age or comorbid conditions, who were treated with fludarabine-based RIC regimens. Donor type was matched related (n =30), 1 antigen-mismatched related (n =4), or matched unrelated (n =30). With median follow-up of 7 years, overall survival (OS) and progression-free survival (PFS) were 33% and 20%, respectively, at 5 years. Incidence of treatment-related mortality (TRM) was 33%, 39%, and 48% at 100 days, and 2 and 5 years after HSCT, respectively. In multivariate analysis, only disease stage at time of HSCT was significantly predictive for both OS and PFS. RIC HSCT provides adequate disease control in chronic-phase CML patients, but alternative treatment strategies need to be explored in patients with advanced disease. TRM rates are acceptable in this high-risk population but increase over time.

Reduced-Intensity Conditioning Versus Conventional Regimen for Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation in Patients with Chronic Myeloid Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5299-5299
Author(s):  
Jianmin Wang ◽  
Weiping Zhang ◽  
Caobo Feng ◽  
Xianmin Song ◽  
Xiong Ni ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Median Time ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Reduced Intensity Conditioning ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Reduced Intensity

Abstract Objective To explore the significance of reduced-intensity conditioning allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) in the treatment of chronic myeloid leukemia. Patients and Methods Twenty-six consecutive patients received reduced-intensity conditioning (Flu 30mg/m2.d−1×5d+BU 4mg.kg−1.d−1×3d or CTX 100mg.kg−1+TBI≤6.0Gy) PBSCT(RIC group). Among them, 21 were male and 5 female with median age of 36 (23~49). Twenty three of them were in chronic phase and 3 in progressive phases. The median time from diagnosis to transplantation was 12 (3~84) months. Twenty-four consecutive patients received standard conditioning (CTX 120mg.kg−1+ TBI≥7.0Gy) prior to PBSCT (STAND group) were used as historic controls. In this group of patients, 22 were in chronic phase and 2 in progressive phases. Twenty patiens were male and 4 female with median age of 35 (18~49). The median time from diagnosis to transplantation was 13 (3~48) months. All patients received PBSC from HLA matched related donors. Mycophenolate mofetil (MMF),CsA and MTX were given for prophylaxis of acute graft-versus-host-disease (aGVHD). Results All patients were successfully engrafted and achieved a complete cytogenetic remission. One patient developed graft rejection 6 months post-transplantation in RIC group. The median time when granulocyte exceeded 0.5 ×109/L and platelets exceeded 20 ×109/L was 15(12–23) days and 19(12–32) days in STAND group and 13(11–18) and 17(11–30) days in RIC group, respectively. The cumulative incidence of aGVHD was 45.83% (11/24) in STAND group and 23.08% (6/26) in RIC group(P>0.05). The incidence of Grade III–IV aGVHD in STAND group and RIC group was 16.67% and 0%, respectively(P<0.05). Chronic GVHD (cGVHD) occurred in 15 out of 20 patients (75%) lived longer than 6 months post-transplantation in STAND group and 18 out of 25 patients (72%) in RIC group(P>0.05). The incidence of extensive cGVHD in STAND group and RIC group was 35% and 0%, respectively(P<0.01). Median follow-up for survivors was 34(14–89)and 18(6–39)months in the STAND and RIC groups, respectively. Relapse occurred in 12.5%(3/24)of the patients in STAND group and 11.54%(3/26)in RIC group (P>0.05). 4 patients experienced a cytogenetic relapse, which was successfully treated with donor PBSC infusions. The Cumulative incidence of TRM was 41.67% (10/24) for the STAND group and 19.23% (5/26) for the RIC group, respectively (P>0.05). GVHD copplicated with interstitial pneumatitis or severe infection were the main causes of death. The estimated 3-year probabilities of disease-free-survival (DFS) was 62% in STAND group and 76% in RIC group, respectively (P>0.05). Conclusion Our results indicate that reduced-intensity conditioning allogeneic peripheral blood stem cells transplantation is a safe, less toxic and curative approach for patients with chronic myeloid leukemia.

Treosulfan, Fludarabine, and Antithymocyte Globulin - A Low Toxicity Conditioning Regimen for Unrelated Donor - Hematopoietic Stem Cell Transplantation in Chronic Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2948-2948
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Giebel ◽  
Jerzy Wojnar ◽  
Miroslaw Markiewicz ◽  
Aleksandra Holowiecka-Goral ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Grade 3

Abstract Unrelated donor - hematopoietic stem cell transplantation (URD-HSCT) is the treatment of proved long-term efficacy for chronic myeloid leukemia (CML) patients not having an HLA-identical sibling. However, high procedure-related toxicity observed after oral busulfan- or TBI-based conditioning limits its applicability and deteriorates outcome [Radich, Blood2003, 102, 31–5]. This is of increasing importance in the presence of challanging options offered by tyrosine kinase inhibitors. Between 2003–2006 we introduced a new preparetive regimen consisting of Treosulfan (a soluble alkylyting agent) 14 g/m2/d on days -6, -5, -4, Fludarabine 30 mg/m2/d on days -6, -5, -4, -3, -2, and, anti-thymocyte globulin (ATG) at a total dose of 6 mg/kg. Thirty patients (age 32, range 16–48 years) with CML in the 1st chronic phase (n=29) or in 2nd chronic phase (n=1) were included in the study. Median interval from diagnosis to alloHSCT equaled 1.0 (0.5–12.0) years. 63% of patients had previously been treated with Imatinib. The donors were selected based on high resolution typing for both HLA class I and II. 43% of donors were mismatched for a single HLA-C (n=9), HLA-DQB1 (n=3) or HLA-B locus (n=1). Bone marrow was used a source of stem cells in 19 patients, peripheral blood - in 11 cases. GVHD prophylaxis consisted of Cyclosporin A and short-course Methotrexate. All patients engrafted with the median time to neutrophil recovery >0.5 G/L and PLT >50 G/L of 19 (10–30) days and 18 (12–29) days, respectively. Complete donor chimerism was achieved until day +100 in all but one patient. Grade 3–4 neutropenic infections occurred in 13% of patients. Grade 3–4 mucositis as well as hepatic toxicity including VOD were not observed. The incidence of grade II acute GVHD was 23%, whereas grade III-IV acute GVHD was not observed. The incidence of extensive chronic GVHD was 10%. At 3 years the probability of the overall survival and hematological relapse-free survival equaled 82% (+/−7%). The cumulative incidence of non-relapse moratlity was 18% (+/−7%) (fungal infection n=3, bacterial infection n=1, EBV-LPD n=1). Four patients required donor lymphocyte infusion or additional interferon or imatinib treatment because of incomplete donor chimerism or molecular/cytogenetic relapse after initial response. We conclude that treosulfan + fludarabine + ATG conditioning is associated with low organ toxicity, low incidence of severe GVHD and NRM. The regimen is feasible option for CML patients referred for URD-HSCT in tyrosine kinase inhibitors era.

Imatinib Mesylate Versus Allogeneic Hematopoietic Stem Cell Transplantation For Patients With Chronic Myeloid Leukemia In Chronic Phase

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5518-5518
Author(s):  
Liu Xiaoli ◽  
Guanlun Gao ◽  
Xuan Zhou ◽  
Na Xu ◽  
Yajuan Xiao ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Imatinib Mesylate ◽  
Hematopoietic Stem Cell ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Hematopoietic Stem ◽  
Risk Patients

Abstract Background and Objective Following the introduction of the tyrosine kinase inhibitor (TKI) imatinib in treatment of chronic myeloid leukemia (CML) patients, the allogeneic hematopoietic stem cell transplantation (allo-HSCT) scene in CML has changed dramatically. This retrospective cohort study was designed to compare medical outcomes of Imatinib mesylate and allo-HSCT for patients with CML in chronic phase. Patients and Methods From February 2002 to February 2012, 198 patients treated consecutively at the Nanfang Hospital,Southern Medical University were assigned to two groups according to treatment with imatinib or allo-HSCT. One hundred fifteen cases of imatinib group were given imatinib at an initial dose of 400mg daily and the dose was then adjusted according to the patient´s blood and therapy response. All the patients were evaluated for hematologic, cytogenetic and molecular response every 1-3months. Eighty-three cases of allo-HSCT group received myeloablative preconditioning regimen, and methotrexate (MTX) and cyclosporine A (CsA) were used for graft-versus-host disease(GVHD), parts combined with mycophenolate mofetil (MMF) and antihuman thymocyte globulin(ATG). The primary end points of the study were complete cytogenetic response (CCyR), relapse rate, overall survival (OS) and progression-free survival (PFS) after therapy. Results In total, 59 (68.9%) patients treated over 12 months achieved a CCyR after 12 months in imatinib group, while 67 (95.7%) patients in allo-HSCT group. The relapse rates were 14.8% (n=17) in imatinib group and 10.8% (n=9) in allo-HSCT group (P=0.456). Ten-year cumulative OS rates were 93.9% in imatinib group and 77.1% in allo-HSCT group(P=0.015) and ten- year cumulative PFS rates of two groups were 86.1% vs.88.0%(P=0.508). For Sokal rating stratified analysis, the ten-year OS rates of two groups were 96.4% vs.68.0% (P = 0.049) for high-risk patients,92.6% vs. 57.1% (P = 0.019) for intermediate-risk patients , while the ten-year PFS rates of two groups were 89.3% vs. 88.0% for high-risk patients (P = 0.942), 70.4% vs. 85.7% for intermediate-risk patients (P = 0.405).The ten-year OS rates and PFS rates were not significant difference for low-risk patients. The cumulative OS rates of two groups were 94.7% vs. 73.5%(P=0.019)for the patients who were not less than 30 years old,and the cumulative PFS rates of two groups were 84.2% vs. 94.1% respectively (P=0.147). Conclusion Imatinib mesylate treatment is superior to allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia in chronic phase. Disclosures: No relevant conflicts of interest to declare.

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