CML ALLO Transplant

More than 90% of patients with chronic myeloid leukemia (CML) have the chromosomal translocation t(9;22)(q34;q11), while 5-8% of patients have complex variant translocations that have previously been thought not to affect the efficacy of imatinib therapy. The present study reports a patient with CML in B-lymphoid blast crisis who had a rare three-way Philadelphia (Ph) variant t(3;9;22)(p21;q34;q11), in addition to isodicentric Ph chromosomes. The patient was initially treated with imatinib for >2 months with a very poor response...

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig® ; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP)...

BACKGROUND: Extramedullary blast crisis (EBC) of T315I BCR-ABL mutated chronic myelogenous leukemia (CML) is extremely rare. METHODS: We report an unusual case characterized by fever, right shoulder swelling, pleural effusion, and multiple bone destruction as the first signs of EBC of T315I BCR-ABL mutated CML. RESULTS: The patient did not respond to chemotherapy consisting of anthracyclines, cytarabine and etoposide. His condition improved after the treatment with ponatinib combined with allogenic stem cell transplantation (alloHCT), but soon worsened after ponatinib withdrawal...

Adolescent and young adult (AYA) patients with hematological malignancy aged 15 to 39 years are recognized as a separate entity, and the efficacy and safety of unrelated cord blood transplantation (CBT) for chronic myeloid leukemia (CML) in AYA patients has not been reported. From March 2002 to June 2015, total of 106 CML patients received allogeneic hematopoietic cell transplantation (allo-HCT) in our center. Included in the present study were CML patients aged 15 to 39 years who received unrelated CBT or sibling allo-HCT, and 74 consecutive AYA patients with CML enrolled in this analysis...

Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and relapse of myeloid neoplasms...

OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated...

Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with chronic myelogenous leukemia in the chronic phase (CML-CP), and outcomes of TKI treatment for patients with CML-CP have been excellent. Since multiple TKIs are currently available, second-line or third-line TKI therapy is considered for patients who are intolerant of or resistant to the previous TKI treatment. Therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered only for patients with disease progression or for patients after treatment failure with multiple TKIs...

BACKGROUND: Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS: A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted...

Allogeneic stem cell transplantation remains the standard treatment for resistant advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Relapse is the major cause of treatment failure in both diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse rates, but concerns regarding their effect on immune reconstitution have been raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL patients who received post-allo-SCT nilotinib...

PURPOSE: To compare the relative merits of imatinib and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML). MATERIALS AND METHODS: This cohort study was designed to compare the outcomes of imatinib (n=292) versus allo-HSCT (n=141) for CML, the clinical data of these patients being retrospectively analyzed so as to compare the event free survival (EFS) and overall survival (OS) between these two groups with patients in the chronic phase (CP) and advanced phases, including accelerate (AP) and blast phases (BP)...

The introduction of tyrosine kinase inhibitors (TKIs) has dramatically changed the management of patients with chronic myeloid leukemia (CML). Despite improved outcomes for most CML patients, disease progression from chronic phase (CP) to accelerated phase (AP) or blast phase (BP) occurs in 1-1.5% of cases per year with current TKI therapy. In addition, about 10-15% of newly diagnosed patients present in AP or BP. Even in the TKI era, the prognosis of patients with advanced-phase CML is not satisfactory. Although de novo AP patients who respond optimally to TKI have excellent outcomes, the prognosis of the remaining advanced-phase CML patients treated with TKI remains poor...

In chronic myeloid leukemia (CML), the occurrence of blastic transformation is rare. Treatment outcome is generally poor. Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative treatment option for advanced-phase CML. Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates are associated with high morbidity and mortality rates, particularly in patients with haematological malignancies. Infection and colonization by these multiresistant bacteria may represent a challenge in SCT recipients for the management of post-transplantation complications, as well as for the eligibility to receive a transplant in patients who acquire the pathogen prior to the procedure...

Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu...

A 58-year-old female was diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (CML) in blast crisis (BC) in 2004. The patient received imatinib, which quickly induced molecular remission, and subsequently underwent bone marrow transplantation (BMT) from an unrelated human leukocyte antigen (HLA)-identical donor. The post-transplant clinical course was essentially uneventful. In 2014, ten years after the BMT, the patient was admitted to our hospital complaining of lymphadenopathy, and blasts were observed in peripheral blood...

OBJECTIVE: To analyze the treatment outcome of a consecutive series of 100 leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of leukemia patients received allo-HSCT were analyzed retrospectively, the therapeutic efficacy was summarized. 100 evaluable cases of leukemia included 47 cases of AML, 33 cases of ALL, 2 cases of AL (biphenotypic), 16 CML and 2 CMML. Before transplantation, 76 cases were in first complete remission, 9 cases in second or greater complete remission and 15 cases in non-remission or relapse...

Allogeneic stem cell transplantation (SCT) is currently the only curative treatment option for chronic myeloid leukemia (CML) patients with BCR-ABL T315I mutations. We report the outcome of SCT in 22 patients with T315I(+) CML, most (n = 16) from haploidentical family donors (HID-SCT). At the time the mutation was detected, 8 patients were in the chronic phase (CP), 7 in the accelerated phase (AP), and 7 in the blast phase (BP). At the time of SCT 7 were in the CP, 8 in the AP or returning to the CP post-AP (AP/AP-CPn), and 7 in the BP or returning to CP post-BP (BP/BP-CPn)...

A second allogeneic (allo) hematopoietic cell transplant (HCT) is an important therapeutic consideration for patients relapsing after their first. We conducted a retrospective review of 41 pediatric patients with leukemia that underwent a second allo-HCT at our institution. Overall, 53.7 and 43.9 % of patients were alive and disease-free at 1 and 5 years, respectively, after the second allo-HCT. The factors affecting outcome by both univariate and multivariate analysis were interval between transplants and the use of a myeloablative conditioning (MAC) regimen prior to second transplant...

The introduction of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) has significantly increased survival rate and quality of life for patients with CML. Despite the high efficacy of imatinib, not all patients benefit from this treatment. Resistance to imatinib can develop from a number of mechanisms. One of the main reasons for treatment failure is a mutation in the BCR-ABL gene, which leads to therapy resistance and clonal evolution. Clearly, new treatment approaches are required for patients who are resistant to imatinib...

BACKGROUND: Chronic myelogenous leukaemia (CML) is a hematopoietic stem cell disease with a relatively stable clinical course. Survival has increased with addition of Tyrosine Kinase inhibitors (TKI's). Its conversion into blast crises (BC) heralds an accelerated clinical course that is less responsive to treatment and has high mortality. METHODS: Clinical records of 20 patients with CML who transformed to BC in two years between January 2012 and December 2013 were reviewed...

Cytomegalovirus (CMV) infection is a major infectious complication after allogeneic hematopoietic cell transplantation (allo-HSCT). Recently, it was reported that CMV reactivation is associated with a decreased risk of relapse in patients with acute myeloid leukemia (AML). The aim of this study was to evaluate the impact of early CMV reactivation on the incidence of disease relapse after allo-HSCT in a large cohort of patients. The Japan Society for Hematopoietic Cell Transplantation's Transplantation-Related Complication Working Group retrospectively surveyed the database of the Transplant Registry Unified Management Program at the Japan Society for Hematopoietic Cell Transplantation...