The Early Referral for Reduced-Intensity Stem Cell Transplantation in Patients with Ph1 (+) Chronic Myelogenous Leukemia in Chronic Phase in the Imatinib Era: Results of the Latin American Cooperative Oncohematology Group (LACOHG) Prospective, Multicenter Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4838-4838
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
David Gomez-Almaguer ◽  
Amelia Morales-Toquero ◽  
Cesar H. Gutierrez-Aguirre ◽  
Jorge Vela-Ojeda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Chronic Myelogenous Leukemia ◽  
Latin American ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Reduced Intensity

Abstract Using a reduced intensity stem cell transplantation (RIST) schedule, 24 patients with Ph1 (+) chronic myelogenous leukemia (CML) in first chronic phase were prospectively allografted in four Latin American countries: Mexico, Brasil, Colombia and Venezuela, using HLA-identical siblings as donors. Median age of the patients was 41 years (range 10 to 71); there were 8 females. Patients received a median of 4.4 x 106/ Kg CD34 cells. Median time to achieve above 0.5 x 109/L granulocytes was 12 days, range 0–41, whereas median time to achieve above 20 x 109/L platelets was also 12 days, range 0–45. Twenty two patients are alive 81 to 830 (median 497) days after the RIST. The 830-day probability of survival is 92%, whereas median survival has not been reached, being above 830 days. Eleven patients (46%) developed acute graft versus-host disease (GVHD), whereas 7 of 23 (30%) developed chronic GVHD. Two patients died 43 and 210 days after the RIST, one as a result of sepsis and the other one of chronic GVHD. The 100-day mortality was 4.4 %, whereas the transplant-related mortality was 8%. RIST for patients with CML in chronic phase seems as an adequate therapeutic option.

scholarly journals The role of stem cell transplantation for chronic myelogenous leukemia in the 21st century

Blood ◽  
2015 ◽  
Vol 125 (21) ◽  
pp. 3230-3235 ◽  
Author(s):  
A. John Barrett ◽  
Sawa Ito
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitors ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Blastic Phase

Abstract The introduction of tyrosine kinase inhibitors (TKIs), a treatment of chronic myelogenous leukemia (CML), has largely replaced curative strategies based on allogeneic stem cell transplantation (SCT). Nevertheless, SCT still remains an option for accelerated/blastic-phase and selected chronic-phase CML. Transplant outcomes can be optimized by peritransplant TKIs, conditioning regimen, BCR-ABL monitoring, and relapse management. Controversies exist in transplant timing, pediatric CML, alternative donors, and economics. SCT continues to serve as a platform of “operational cure” for CML with TKIs and immunotherapies.

Allogeneic Hematopoietic Stem Cell Transplantation with Nonmyeloablative Conditioning in Patients with Myeloid Leukemias: Results of a Prospective Study of the Latin American Cooperative Onco Hematology Group (LACOHG).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5154-5154
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
David Gómez-Almaguer ◽  
José D. Gómez-Rangel ◽  
Jorge Vela-Ojeda ◽  
Amado Kardus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Latin American ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Transplant Survival ◽  
Post Transplant

Abstract Using a nonmyeloablative stem cell transplantation (NST) program previously shown to be effective in individuals receiving allografts in México, 29 patients with either acute myelogenous leukemia (AML, n = 12) or chronic myeloid leukemia (CML, n = 17) from the Latin American Cooperative Onco Hematology Group (LACOHG) were prospectively given allogeneic bone marrow allografts. Patients received a modified NST conditioning regimen consisting of oral busulphan 4 mg/kg on Days −6 and −5, IV cyclophosphamide 350 mg/m2 on Days −4, −3, and −2, IV fludarabine 30 mg/m2 on Days −4, −3, and −2, oral cyclosporine A 5 mg/kg twice daily starting on Day −1 (continuing until Day 180), and IV methotrexate 5 mg/m2 on Days +1, +3, +5, and +11. Median patient age was 43 years (range, 10–63). All patients engrafted; median time to achieve an absolute neutrophil count >0.5 x 109/L was 14 days (range, 0–21), whereas the median time to achieve a platelet count >20 x 109/L was 12 days (range, 0–21). Follow-up periods ranged between 39 and 519 days (median, 249). In patients with CML, the median overall post-transplant survival has not been reached, whereas the 519-day overall survival was 88%, and the 100-day mortality was 0%. In patients with AML, the median overall post-transplant survival has not been reached, the 459-day overall survival was 66%, and the 100-day mortality was 8%. The results from this multicenter, multinational study complement and further support the efficacy of our NST preparative regimen. The initial experience obtained from individuals with CML and AML receiving allografts in 2 institutions in México has now been extended into other Latin American countries, and the results are acceptable.

Response to Tyrosine Kinase Inhibitors Therapy and Donor Lymphocyte Infusion In Patients with Chronic Myelogenous Leukemia Relapsing After Allogenic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4482-4482
Author(s):  
Malgorzata Sobczyk-Kruszelnicka ◽  
Tomasz Czerw ◽  
Anna Waclawik ◽  
Ryszard Wichary ◽  
Wlodzimierz Mendrek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Chronic Myelogenous Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Donor Chimerism

Abstract Abstract 4482 Tyrosine kinase inhibitors (TKIs) and donor limfocyte infusion (DLI) are nowadays possible treatment options to treat relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (alloHSCT). This report aim was to analyze management and outome of CML relapse after alloHSCT based on single centre experience. We retrospectively reviewed 8 patients treated with TKIs and/or DLI for CML relapse after alloHSCT. Study group chracteristic before transplantation: 8 patients (4 women, 4 men); median age 31 years (25-53); disease duration before alloHSCT 10 months (4-33); prior transplantation treatment: imatinib (n=8), nilotinib (n=1); CML phase: chronic phase 1 (n=7), chronic phase 2 (n=1); remission status: hematological (n=8), cytogenetic (n=4), molecular (n=3); donor type (identical sibling – 4, matched unrelated –3, 1 HLA-antigen mismatched unrelated – 1); stem cell source (bone marrow – 7, peripheral blood – 1); conditioning regimen (treosulfan and fludarabine – 7; busulfan and cyclophosphamide – 1); EBMT transplant risk score 2.5 (1-5). All transplantations were performed in intensive care, sterile air units. Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine A and short course of standard dose methotrexate. The median number of transplanted cells: nucleated cells 3.3 × 10^8 (2.1-8.9); CD34(+) cells 3.6 × 10^6 (0.8-12.9); CD3(+) cells 19.3 × 10^6 (17.6-237)/kg recipient body weight. All patients engrafted and achieved full donor chimerism before day 100 after transplantation. Hematopoietic recovery was as follows: leukocytes to 1,0 G/l – median 21 days (12-39); granulocytes to 0,5 G/l - 21 (12-42); platelets to 50 G/l –23 (18-38). Only 3 patients had signs of acute GvHD – grade I (1pt – skin 2 degree; 2pts – skin 1 degree). 8 patients relapsed at median time 5 months after HSCT (4-24). Type of relapse: hematologic –0, cytogenetic-4, molecular – 8. At the time of relapse four patients were still treated with immunosuppressive agents. The median donor chimerism at the relapse was 90% (40-100%) and in 5 cases was lower than 95%. All patients who relapsed started treatment with TKIs (imatinib-7; nilotinib-1). The madian treatment time is 10 months (2-50). Four of them are still treated with TKIs. Seven patients recieved also DLI – median 1.5 times (1-6). 7 of 8 patients patients achieved molecular remission and 1 patient a complete cytogenetic response. All patients who achieved remission showed evidence of conversion to complete donor chimerism. DLI have become the treatment of choise for CML patients who relapsed after allogenic HSCT. An alternative to DLI are now TKIs: imatinib or second line TKIs. Is the DLI still the “gold standard”? Or better chose only TKIs to achieve remission without the risk of GvHD? Or chose the combination with lower doses of DLI to maximise responses while minimising the risk of GvHD? We are still looking for optimal and most effective treatment option for these patients. Disclosures: No relevant conflicts of interest to declare.

Non-Myeloablative Allogeneic Stem Cell Transplantation in 154 Patients (pts) with Chronic Myeloid Leukaemia (CML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4975-4975
Author(s):  
Malek Benakli ◽  
Rose-Marie Hamladji ◽  
Redhouane Ahmed Nacer ◽  
Amina Talbi ◽  
Farih Mehdid ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Chronic Phase ◽  
Transfusion Requirements

Abstract Background: Allogeneic stem cell transplantation using a reduced intensity or nonmyeloablative conditioning (NSCT) represents an attractive treatment modality in CML. The rationale behind such approach is to decrease toxicity while inducing the graft-versus-leukemia (GVL) effect. Because of its significantly lower cost in comparison to Imatinib mesylate, NSCT may be considered an early treatment option in countries where limited resources. Material and Methods: Between April 2001 and December 2006, we treated 154 CML patients (131 in first chronic phase, 23 in accelerated phase) with NSCT from an HLA-identical family donor. The majority of pts has a Gratwohl score <2 prior to NSCT (n=115; 74,6%). The conditioning regimen included Fludarabine 150 mg/m2 and oral Busulfan 8 mg /kg (139 pts). GVHD prophylaxis consisted of association ciclosporine (CSA)-Mycophenolate (MMF). 15 pts received an additional prophylaxis with antithymocyte globulin (ATG). Median age was 35 (range, 18–55) years, and the sex-ratio (M/F) 0,87. The median time from diagnosis to NSCT was 11 (range, 4–50) months. All pts received G-CSF mobilised peripheral blood stem cells, median CD34+ cells count: 7,02.106/kg (range, 1,28–44,9). Results: Leucopenia is found almost at 71 pts (46,1%). The median time to achieve ANC >500. 109/l granulocytes was 14 (range, 7–24) days, and median time of aplasia was 7 (range, 2–19) days. Transfusion requirements were significantly reduced, only 3 pts (1,9%) required red blood cells transfusions. Only 15 pts (9,7%) needed platelets transfusions. Acute GVHD was seen in 65 cases (43,6%) including 26 (17,4%) cases of grade III–IV and 32 cases (21%) of late onset acute GVHD occurring after day 100 post-NSCT. 93 pts (67,3%) had chronic GVHD, of whom 58 with an extensive form. 23 pts (15,4%) had CMV reactivation. 24 pts (16,1%) relapsed (15 in chronic phase, 7 in blast crisis and 2 with a molecular relapse), but 11 pts could be salvaged and are currently in remission (7 after immunosupression discontinuation, one after DLI and 3 after a second conventional allograft). The chimerism of donor origin (STR-PCR method) of patients in remission was at an average of 74% at day 30, 80% at d100, 93% at 6 months, 97% at 1 year, and 99% at 2 years. Fifty pts (33,5%) have died, of whom 39 (22,1%) from GVHD and 10 (6,7%) from disease relapse. Transplant Related Mortality (TRM) at 100 days was 6%, but rose to 31,5% at 3 years. At last follow-up (median, 32 (range 6–68) months), 99 pts (66,4%) are still alive, 97 (65,1%) pts in hematologic remission; of whom 76 (78,3%) in complete molecular remission evaluated by RT-PCR. Overall survival and progression-free survival at 5 years are 61% and 51,6% respectively. Conclusion. The study demonstrates a relatively low rate of short-term toxicities after NSCT. However, long-term TRM is still high because of the GVHD. The GVL effect is well admited. The relapse can be often controled by immunomodulation (stoppage of immunosuppression, DLI) and eventually by second myeloablative allograft.

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