Management of Chronic Myeloid Leukemia with BCR/ABL Inhibitors: Current Status and Future Perspectives

2010 ◽  
Vol 2 ◽  
pp. CMT.S2439
Author(s):  
Peter Valent
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Current Status ◽  
Drug Resistant ◽  
Intrinsic Resistance ◽  
Hematopoietic Stem ◽  
Co Morbidity

Chronic myeloid leukemia (CML) is a hematopoietic neoplasm characterized by the Philadelphia chromosome (Ph) and the BCR/ABL oncoprotein. In chronic phase (CP) CML, leukemic cells display multilineage differentiation and maturation capacity. The BCR/ABL inhibitor imatinib exerts profound antileukemic effects in these patients and is considered standard frontline therapy. However, not all patients show a long-lasting response to this drug. Rather, resistance to imatinib has been recognized as an emerging clinical problem in CML. While CML stem cells exhibit intrinsic resistance against imatinib and thus survive therapy, one or more stem cell-derived subclones may acquire additional hits over time, so that an overt relapse occurs. A major triggering hit in such subclones are BCR/ABL mutations. For these patients, novel multikinase inhibitors targeting BCR/ABL such as nilotinib, dasatinib, bosutinib, bafetinib, as well as Aurora kinase inhibitors have been developed and shown to exert antileukemic effects in imatinib-resistant CML. In addition, hematopoietic stem cell transplantation (HSCT) remains an important treatment option for drug-resistant patients. The decision concerning second- or third line therapy, selection of drugs, and HSCT, is usually based on the presence and type of BCR/ABL mutation(s), phase of disease, other disease-related factors, and patient-related variables including age and co-morbidity. The current article provides an overview on current diagnostic and therapeutic strategies for patients with drug-naïve and drug-resistant CML.

Stem cell transplantation for chronic myeloid leukemia in children

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1224-1231 ◽  
Author(s):  
Kate Cwynarski ◽  
Irene A. G. Roberts ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Ronald Brand ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Disease Stage ◽  
Hematopoietic Stem ◽  
Advanced Phase

Abstract Hematopoietic stem cell transplantation (SCT) is the only proven cure for chronic myeloid leukemia (CML), a rare disease in childhood. We report outcomes of 314 children with Philadelphia-chromosome–positive (Ph+) CML undergoing SCT from HLA-matched siblings (n = 182) or volunteer-unrelated donors (VUD; n = 132). Three-year overall survival (OS) and leukemia-free survival (LFS) rates were 66% and 55% (n = 314). For 156 children in first chronic phase (CP1) who underwent transplantation from HLA-identical siblings, OS and LFS rates were 75% and 63%. For 97 children who underwent SCT in CP1 from VUD, 3-year OS and LFS rates were 65% and 56%, reflecting higher transplantation-related mortality (TRM) after VUD SCT (35% vs 20%; multivariate hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.0-3.5; P = .05). In a multivariate model for OS and LFS, outcomes were superior in CP1 than in advanced phase (AP/CP1) (OS HR, 2.0; 95% CI, 1.3-3; P = .001; LFS HR, 1.8; 95% CI, 1.2-2.6; P = .003). For relapse, donor source (VUD/sibling) (HR, 0.38; 95% CI, 0.19-0.76; P = .006) and disease stage (AP/CP1) (HR, 2.4; 95% CI, 1.36-4.3; P = .003) were significant. This is the first large series to show that SCT confers long-term LFS in most children with CML and helps assess alternative therapy, including tyrosine kinase inhibitors.

scholarly journals Stem Cell Factor as a Single Agent Induces Selective Proliferation of the Philadelphia Chromosome Positive Fraction of Chronic Myeloid Leukemia CD34+ Cells

Blood ◽  
1998 ◽  
Vol 92 (7) ◽  
pp. 2461-2470 ◽  
Author(s):  
Sarah Moore ◽  
David N. Haylock ◽  
Jean-Pierre Lévesque ◽  
Louise A. McDiarmid ◽  
Leanne M. Samels ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Factor ◽  
Myeloid Leukemia ◽  
Single Agent ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Leukemic Cell ◽  
Proliferative Effect ◽  
Cd34 Cells

Abstract The interaction between p145c-KIT and p210bcr-abl in transduced cell lines, and the selective outgrowth of normal progenitors during long-term culture of chronic myeloid leukemia (CML) cells on stroma deficient in stem-cell factor (SCF) suggests that the response of CML cells to SCF may be abnormal. We examined the proliferative effect of SCF(100 ng/mL), provided as the sole stimulus, on individual CD34+ cells from five normal donors and five chronic-phase CML patients. Forty-eight percent of isolated single CML CD34+ cells proliferated after 6 days of culture to a mean of 18 cells, whereas only 8% of normal CD34+ cells proliferated (mean number of cells generated was 4). SCF, as a single agent, supported the survival and expansion of colony-forming unit–granulocyte-macrophage (CFU-GM) from CML CD34+CD38+ cells and the more primitive CML CD34+CD38− cells. These CFU-GM colonies were all bcr-abl positive, showing the specificity of SCF stimulation for the leukemic cell population. Coculture of CML and normal CD34+ cells showed exclusive growth of Ph+cells, suggesting that growth in SCF alone is not dependent on secretion of cytokines by CML cells. SCF augmentation of β1-integrin–mediated adhesion of CML CD34+cells to fibronectin was not increased when compared with the effect on normal CD34+ cells, suggesting that the proliferative and adhesive responses resulting from SCF stimulation are uncoupled. The increased proliferation may contribute to the accumulation of leukemic progenitors, which is a feature of CML.

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.

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.

HLA-Haploidentical Related Hematopoietic Stem Cell Transplantation and Mesenchymal Stem Cell Transplantation in Patients with Hematologic Malignancies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5408-5408
Author(s):  
Xiaoyan Zhang ◽  
Jianyong Li ◽  
Kejiang Cao ◽  
Hanxin Wu ◽  
Hua Lu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Features ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only way to cure many hematologic malignancies. HLA-haploidentical related HSCT was performed in case of lack of HLA-matched donors. From the results of in-vitro and animal studies, Mesenchymal stem cells (MSCs) transplanted simultaneously with hematopoietic stem cells (HSCs) may support hematopoietic regeneration and have the immunomodulatory effect. MSCs together with HSCs transplantation from the same HLA-haploidentical donor were used in patients with hematologic malignancies. Patients and Methods: Three patients were chronic myeloid leukemia (blast crisis), chronic myeloid leukemia (chronic phase) and refractory T-cell lymphoblastic lymphoma (leukemia phase) respectively. Complete demographic and clinical details of these 3 patients are shown in Table 1. Bone marrow mononuclear cells obtained from their HLA-haploidentical related donors were cultured and expanded in vitro about 2 months before transplantation. Immunophenotype of the harvested cells were detected in order to identify them. After conditioned by cytosine arabinoside/cyclophosphamide/total body irradiation regimen, patients were co-transplanted with HSCs and ex-vivo expanded MSCs. Cyclosporine, methotrexate, antithymocyte globulin, mycophenolate mofetil and anti-CD25 monoclonal antibody were used together for prophylaxis of GVHD. Clinical features after transplantation in these patients were observed. Results: About 2×106 MSCs per kilogram of recipients’ weight were successfully expanded from bone marrow samples. These cells were CD73, CD90, CD105 positive and CD34, CD45, CD38, CD10, CD20, CD33, HLA-DR negative by flow cytometric analysis. No adverse response was observed during and after infusion of MSCs. Hematopoietic reconstruction was successful in all the patients. And they had full donor-type chimerism 1 month after transplantation. N1 received donor lymphocyte infusion (DLI) to prevent the relapse. N2 relapsed and received the therapy of STI571 combined with DLI. She had a complete remission at last. No graft-versus-host disease (GVHD) was observed in N1 and N2 until they received DLI. N1 died of infection 11 months after transplantation. N2 and N3 now have been followed up for 41 and 31 months respectively. Clinical features of patients after transplantation are shown in Table 2. Conclusions: Bone marrow derived MSCs can be tolerant well in HLA-haploidentical HSCT. Its exact effect in human HLA-haploidentical allogeneic HSCT needs to be studied further. Tab.1 Patient Demographic and Clinical Data Patient Diagnosis Age Sex Course of disease before transplantation Donor Mismatched HLA loci Abbr: LPL - lymphoblastic lymphoma; CML - chronic myeloid leukemia; BC - blast crisis; CP - chronic phase; yr - year; mo - month N1 T-LPL 22 F 7 yr mother 3 N2 CML-BC 32 F 6mo sibling brother 3 N3 CML-CP 22 M 5mo father 3 Tab.2 Clinical features of patients after transplantation Patient Hematopoietic reconstruction Donor-type chimerism Time of relapse time of DLI acute GVHD chronic GVHD survival Abbr: DLI - donor lymphocyte infusion; d - day; mo - month N1 15 d 100% no 5 mo IV (after DLI) extensive die in 11 mo N2 16 d 100% 6mo 6 mo IV (after DLI) no >41 mo N3 15 d 100% no no I limited >31 mo

Significance of Minimal Residual Disease in Patients with Chronic Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3269-3269
Author(s):  
Iwona Solarska ◽  
Barbara Nasilowska-Adamska ◽  
Maria Bieniaszewska ◽  
Jan Maciej Zaucha ◽  
Piotr Rzepecki ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Chronic Phase ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Low Level ◽  
High Level ◽  
Minimal Residual

Abstract Abstract 3269 Poster Board III-1 Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for patients (pts) with chronic myeloid leukemia (CML). AlloHSCT is associated with long-term disease-free survival in 40% to 80% pts transplanted in early chronic phase of disease. The probability of relapse for pts transplanted in first chronic phase is 10% to 20% at 5 years, and is even higher (30% – 60%) for pts who received transplant in advanced phases of CML. The significance of minimal residual disease (MRD) in this clinical setting is uncertain. We enrolled 63 consecutive pts with CML who had received an alloHSCT between 1995 and 2007 and had BCR-ABL transcript quantity measured by RQ-PCR method on at least 2 occasions during follow-up in the period starting 6 months after alloHSCT. The reverse transcription was preformed using SuperScriptIII and random hexamers. Quantification of BCR-ABL was performed by RQ-PCR assay according to ‘Europe Against Cancer' protocol. BCR-ABL expression was normalized with endogenous control ABL gene and expressed as a ratio BCR-ABL/ABL. According to the amount of BCR-ABL transcript detected in blood or bone marrow after alloHSCT pts were allocated into 3 categories, including pts with no-detectable or stable very low-level of BCR-ABL transcripts (ratio BCR-ABL/ABL below 0.005%), pts with fluctuating-low level of BCR-ABL transcripts (0.005 – 0.01%) and pts with high-level of BCR-ABL transcripts (0.01 – 0.1%). We didn't find any relationships between different BCR-ABL levels after alloHSCT and clinical parameters at the time of CML diagnosis or transplantation, including Sokal, Hasford and Gratwohl scores. Median time from alloHSCT to molecular relapse (MR) was 38 months (range, 8.5 – 88.5 months). The 3-year progression rate into cytogenetic or hematological relapse of CML since MR was 70%. This progression occurred at a median time of 1.4 months (range, 0 – 3.2 months). We found strong correlation between the levels of BCR-ABL transcripts after alloHSCT and a risk of relapse. The incidence of MR was 0%, 26%, 71% for the low-level, fluctuating-low level and high-level of BCR-ABL transcript (p<.0001), respectively. Similarly the risk of cytogenetic and hematological relapse was 0%, 21%, 43% for these pts (p=.001), respectively. Five-year leukemia-free survival was 100%, 83.9% and 66.7% for the pts with low-level, fluctuating-low level and high-level BCR-ABL transcript (p=.003), respectively. There was no apparent relationship between the level of BCR-ABL transcript and overall survival. We conclude that pts with fluctuating-low and/or high levels of BCR-ABL transcripts are at higher risk of disease progression. Sequential RQ-PCR monitoring coupled with pre-emptive therapy can provide a valid strategy to reduce rates of relapse and development of a more individualized approach to management of pts with CML in major molecular response after alloHSCT. Disclosures: Warzocha: BMS: Consultancy, Honoraria; Celgene: Consultancy; Roche: Honoraria; Pfizer: Honoraria; Amgen: Honoraria.

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.

Three decades of transplantation for chronic myeloid leukemia: what have we learned?

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 755-763 ◽  
Author(s):  
Jiří Pavlů ◽  
Richard M. Szydlo ◽  
John M. Goldman ◽  
Jane F. Apperley
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Hematopoietic Stem

Abstract Last year marked 30 years of hematopoietic stem cell transplantation as a curative treatment of chronic myeloid leukemia (CML). Initially studies used stem cells from identical twins but techniques rapidly developed to use cells first from HLA-identical siblings and later unrelated donors. During the 1990s CML became the most frequent indication for allogeneic transplantation worldwide. This, together with the relative biologic homogeneity of CML in chronic phase, its responsiveness to graft-versus-leukemia effect and the ability to monitor low level residual disease placed CML at the forefront of research into different strategies of stem cell transplantation. The introduction of BCR-ABL1 tyrosine kinase inhibitors during the last decade resulted in long-term disease control in the majority of patients with CML. In those who fail to respond and/or develop intolerance to these agents, transplantation remains an effective therapeutic solution. The combination of tyrosine kinase inhibitors with transplantation is an exciting new strategy and it provides inspiration for similar approaches in other malignancies.

scholarly journals Chronic Myeloid Leukemia Relapsing 25 Years after Allogenic Stem Cell Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Håkon Reikvam ◽  
Jørn Skavland ◽  
Stein-Erik Gullaksen ◽  
Randi Hovland ◽  
Tobias Gedde-Dahl ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Allogenic Stem Cell Transplantation ◽  
Relapsed Disease

Chronic myeloid leukemia (CML) is a myeloproliferative disorder in which neoplastic cells exhibit the Philadelphia chromosome and the related oncoproteinBCR-ABL1. Allogeneic stem cell transplantation (allo-SCT) was considered the first-line treatment for CML, before the introduction of tyrosine kinase inhibitors (TKIs). However, patients are at risk for relapse years after transplantation. We present a patient who relapsed 25 years after allo-SCT for chronic phase CML. Polymerase chain reaction (PCR) detected gradually evaluated levels ofBCR-ABL1transcripts, eventually leading to the diagnosis of relapsed disease. Additional mutational analyses did not reveal mutations in theBCR-ABL1gene, or other cooperating mutations. The patient was successfully treated with imatinib 400 mg daily, leading to new molecular remission. The case presentation emphasizes the need for long-term follow-up of such patients and the potential benefit of initiating TKI treatment with early signs of relapse.

Sign in / Sign up

Export Citation Format

Share Document