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CML ALLO Transplant

Akira Kitanaka
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...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Bulent Kantarcioglu, Huseyin Saffet Bekoz, Fatih Erkam Olgun, Beytullah Cakal, Burak Arkan, Halil Turkoglu, Ali Mert, Deniz Sargin
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...
October 2016: Molecular and Clinical Oncology
Gheath Alatrash, Peter F Thall, Benigno C Valdez, Patricia S Fox, Jing Ning, Haven R Garber, Selma Janbey, Laura L Worth, Uday Popat, Chitra Hosing, Amin M Alousi, Partow Kebriaei, Elizabeth J Shpall, Roy B Jones, Marcos de Lima, Gabriela Rondon, Julianne Chen, Richard E Champlin, Borje S Andersson
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...
October 2016: Biology of Blood and Marrow Transplantation
Yutaro Hino, Noriko Doki, Keita Yamamoto, Yasushi Senoo, Satoshi Sasajima, Masahiro Sakaguchi, Keiichiro Hattori, Satoshi Kaito, Shuhei Kurosawa, Kaito Harada, Shuntaro Ikegawa, Daisuke Watanabe, Takeshi Hagino, Kosuke Yoshioka, Kyoko Watakabe, Aiko Igarashi, Yuho Najima, Takeshi Kobayashi, Kazuhiko Kakihana, Hisashi Sakamaki, Kazuteru Ohashi
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...
May 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Qing-Xin Huang, San-Fang Tu, Rui Huang, Yu-Xian Huang, Lan Deng, Bing-Yi Wu, Chao-Yang Song, Yu-Hua Li
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...
April 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Lan-Ping Xu, Zheng-Li Xu, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Wei Han, Yao Chen, Feng-Rong Wang, Jing-Zhi Wang, Yu Wang, Chen-Hua Yan, Xiao-Dong Mo, Kai-Yan Liu, Xiao-Jun Huang
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)...
June 2016: Biology of Blood and Marrow Transplantation
Neethu N Menon, Lydia M Jenkins, Haiyan Cui, Craig Jenkins, Faiz Anwer, Andrew M Yeager, Emmanuel Katsanis
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...
March 2016: Annals of Hematology
E V Morozova, Y Y Vlasova, M V Pryanishnikova, K V Lepik, B V Afanasyev
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...
2015: Biomarker Insights
Sohail Sarwar, Neelam Siddiqui, Waleed Zafar, Sameer Fasih, Abdul Basit, Abdul Hameed
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...
April 2015: Journal of Ayub Medical College, Abbottabad: JAMC
Katsuto Takenaka, Tetsuya Nishida, Yuki Asano-Mori, Kumi Oshima, Kazuteru Ohashi, Takehiko Mori, Heiwa Kanamori, Koichi Miyamura, Chiaki Kato, Naoki Kobayashi, Naoyuki Uchida, Hirohisa Nakamae, Tatsuo Ichinohe, Yasuo Morishima, Ritsuro Suzuki, Takuhiro Yamaguchi, Takahiro Fukuda
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...
November 2015: Biology of Blood and Marrow Transplantation
Lanping Xu, Huanling Zhu, Jianda Hu, Depei Wu, Hao Jiang, Qian Jiang, Xiaojun Huang
In the tyrosine kinase inhibitor (TKI) era, imatinib is the first-line therapy for patients with chronic myeloid leukemia (CML) in chronic or accelerated phase. Although second-generation TKIs (TKI2), including dasatinib and nilotinib, are appropriate treatment regimens for patients with disease that progressed to accelerated phase following imatinib therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy. This study retrospectively analyzed the efficacy of TKI2 and HSCT for treatment of CML in accelerated phase...
September 2015: Frontiers of Medicine
Kefeng Shen, Qifa Liu, Jing Sun, Qianli Jiang, Yanyan Ye, Hao Huang, Fanyi Meng, Yongjun Zhou, Mo Yang
OBJECTIVE: We conducted a retrospective single-center study of 106 patients to investigate the impact of prior exposure to imatinib before allogeneic hematopoietic stem cell transplantation (allo-HSCT) on outcome of HSCT for chronic myeloid leukemia (CML) in china. METHODS: Patients were divided into imatinib and non-imatinib group according to whether receiving imatinib therapy before transplantation or not. Hematopoietic engraftment, prognosis, congestive heart failure (CHF), hepatic veno-occlusive disease (HVOD), graft versus host disease (GVHD), hemorrhagic cystitis and infections were compared between the two groups in early stage of transplantation (within 100 days after transplantation)...
2015: International Journal of Clinical and Experimental Medicine
M Konopleva, C B Benton, P F Thall, Z Zeng, E Shpall, S Ciurea, P Kebriaei, A Alousi, U Popat, P Anderlini, Y Nieto, S Parmar, W Qiao, J Chen, G Rondon, B McMullin, R-Y Wang, H Lu, W Schober, G Woodworth, A Gulbis, R Cool, M Andreeff, R Champlin
We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day -9) plus plerixafor (doses of 0, 80, 160 or 240 μg/kg daily for 4 days starting on day -7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen...
July 2015: Bone Marrow Transplantation
S Saußele, Richard T Silver
Due to the high efficacy of BCR-ABL tyrosine kinase inhibition (TKI) in chronic phase (CP) chronic myeloid leukemia (CML), the frequency of blast crisis (BC) is greatly reduced compared to the pre-TKI era. However, TKI treatment of BC has only marginally improved the number of favorable responses, including remissions, which for the most part have only been transitory. Occasionally, they provide a therapeutic window to perform an allogeneic stem cell transplantation (allo-SCT). The challenge remains to improve management of BC with the limited options available...
April 2015: Annals of Hematology
Ke-Feng Shen, Qian-Li Jiang, Qi-Fa Liu, Jing Sun, Huai-Ming Wang, Dan Xu, Yu Zhang, Zhi-Ping Fan, Fen Huang, Hong-Sheng Zhou, Xiao-Fang Li, Yong-Qiang Wei, Min Dai, Fan-Yi Meng, Mo Yang
OBJECTIVE: The study was to analyze the acute heart failure's risk factors and clinical characteristics for the patient with chronic myelogenous leukemia (CML) during the early stage (within 100 d) of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 106 cases of CML received allo-HSCT were retrospectively studied in Nanfang Hospital from May 2003 to May 2013. On the basis of existence or absence of acute heart failure during early stage of allo-HSCT (100 d), the patients were divided into heart failure (15 cases) and control group (91 cases)...
February 2015: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jolanta Skalska-Sadowska, Danuta Januszkiewicz-Lewandowska, Katarzyna Derwich, Anna Pieczonka, Magdalena Samborska, Jacek Wachowiak
Few patients in remission of Ph-positive chronic myelogenous leukemia (CML) develop Ph-negative MDS/AML, usually with clonal cytogenetic abnormalities. Isolated Ph-negative myeloid sarcoma (MS) is presented here as a form of such disorder, different from Ph-positive MS establishing CML relapse in blastic phase. We describe 11-year-old male who developed Ph-negative isolated MS with NPM1 mutation, remaining in complete molecular remission of Ph-positive chronic myeloid leukemia treated with allo-HSCT in first chronic phase and with imatinib and donor lymphocyte infusion in molecular relapse...
June 2015: Pediatric Blood & Cancer
Liyu Wang, Huilan Liu, Changcheng Zheng, Baolin Tang, Xiaoyu Zhu, Wen Yao, Lei Zhang, Zimin Sun
OBJECTIVE: To explore the therapeutic efficacy of allo-geneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) patients with T315I mutation. METHODS: Retrospective analyses were conducted for 4 patients with T315I mutation of CML undergoing allo-HSCT from June 2012 to January 2014, including 2 cases in acceleration phase and 2 in chronic phase. There were 2 males and 2 females with ages from 26 to 45 years. Two patients received HLA-matched sibling allo-geneic peripheral blood stem cell transplantation (allo-PBSCT) while another 2 unrelated cord blood stem cell transplantation (UCBT)...
November 4, 2014: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Yao Chen, Lanping Xu, Daihong Liu, Kaiyan Liu, Huan Chen, Xiaohui Zhang, Fengrong Wang, Jingzhi Wang, Yu Wang, Wei Han, Yuhong Chen, Chenhua Yan, Ting Zhao, Xiaojun Huang
OBJECTIVE: To investigate the impact of body mass index (BMI) before transplantation on clinical outcomes of haploidentical allogeneic stem cell transplantation (allo-HSCT). METHODS: We performed a retrospective cohort study of 253 adult patients with acute or chronic leukemia who received haploidentical allo-HSCT from August 2008 to September 2011. All conditioning regimens were myeloablative and bulsufan based. Patients were stratified according to BMI values (low BMI group: <18 kg/m(2); normal BMI group: ≥ 18 and < 25 kg/m(2); overweight BMI group: ≥ 25 kg/m(2))...
September 2014: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
Xiaojin Cai, Jialing Wei, Yi He, Dongling Yang, Erlie Jiang, Yong Huang, Mingzhe Han, Sizhou Feng
BACKGROUND: Busulfan/cyclophosphamide (Bu/Cy) is commonly used as a standard conditioning regimen without total body irradiation for patients with hematological myeloid malignancies undergoing hematopoietic stem cell transplantation (HSCT). OBJECTIVE: To develop a new myeloablative conditioning regimen incorporating fludarabine (Flu) and cytarabine (Ara-c). SETTING: A tertiary blood disease hospital in Tianjin, China. METHODS: A Bu/Cy preparative regimen was used, modified by Flu 90 mg/m(2) and Ara-c 6 g/m(2) in 57 unselected patients (median age 37 years) with hematological myeloid malignancies...
February 2015: International Journal of Clinical Pharmacy
N A Jain, S Ito, X Tian, R Kurlander, M Battiwalla, K Lu, B N Savani, V Malkovska, K Rezvani, R Q Le, A Shenoy, C S Hourigan, K Keyvanfar, E Koklanaris, J Superata, P Muranski, A J Barrett, A S M Yong
Although there are now fewer allo-SCTs performed for CML, leukemic relapse post transplant remains a persistent problem. To better define clinical and biological parameters determining postrelapse outcome, we studied 59 patients with CML relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen (30.5%) were transplanted in advanced phase and 41 (69.5%) in chronic phase. With a median follow-up from relapse of 7.9 years, 5-year post relapse survival (PRS) was 62%. Multivariate analysis found disease status at transplant, time to diagnosis of relapse from transplant and pretransplant tyrosine kinase inhibitor (TKI) use as significant factors associated with PRS...
February 2015: Bone Marrow Transplantation
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