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

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.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4482-4482
Author(s):  
Malgorzata Sobczyk-Kruszelnicka ◽  
Tomasz Czerw ◽  
Anna Waclawik ◽  
Ryszard Wichary ◽  
Wlodzimierz Mendrek ◽  
...  

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.


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 ◽  
...  

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.


Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3641-3647 ◽  
Author(s):  
Elias Jabbour ◽  
Jorge Cortes ◽  
Fabio P. S. Santos ◽  
Dan Jones ◽  
Susan O'Brien ◽  
...  

Abstract Hematopoietic stem cell transplantation (HSCT) is effective therapy for patients with chronic myelogenous leukemia (CML) but is now mostly indicated for patients who develop resistance to tyrosine kinase inhibitors (TKIs), which can be associated with point mutations in BCR-ABL1. We reviewed the outcomes of imatinib-resistant CML patients (chronic phase, n = 34; accelerated phase [AP], n = 9; and blast phase [BP], n = 4) who underwent HSCT and had BCR-ABL1 sequencing. Mutations were found in 19 patients (40%); 15 of 19 had advanced CML (AP + BP + second chronic phase). Patients with mutations were more likely to transform to AP/BP at time of imatinib failure (69% vs 35%, P = .03). Forty-two patients (89%) responded to HSCT: 32 (68%) had at least a major molecular response. The 2-year event-free survival was 36% and 58% (P = .05) for the mutant and nonmutant groups, respectively; and the 2-year overall survival was 44% and 76% (P = .02), respectively. HSCT is an important salvage option for TKI-resistant patients with or without BCR-ABL1 mutations. Patients with mutations were more likely to develop advanced disease and had worse outcomes after HSCT. HSCT should be considered early for patients deemed to have a low probability of responding to second-generation TKI.


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