Posted by rob on October 22, 2010 under Uncategorized | 
The IFNG (IFN-{gamma}) Genotype Predicts Cytogenetic and Molecular Response to Imatinib Therapy in Chronic Myeloid Leukemia.
Clin Cancer Res. 2010 Oct 19;
Authors: Kim DH, Kong JH, Byeun JY, Jung CW, Xu W, Liu X, Kamel-Reid S, Kim YK, Kim HJ, Lipton JH
PURPOSE: The present study analyzed treatment outcomes of imatinib therapy by interindividual genetic variants in candidate biological pathways of chronic myeloid leukemia (CML) such as apoptosis, angiogenesis, IFN-? signaling pathways, or drug transport/metabolism of imatinib. EXPERIMENTAL DESIGN: Peripheral blood DNAs were genotyped for 79 single nucleotide polymorphism markers involved in the pathways of apoptosis, angiogenesis, myeloid cell growth, xenobiotic metabolism, WT1 signaling, IFN signaling, and others in CML patients who were included in discovery (n = 229, Canada) and validation cohorts (n = 187, Korea). RESULTS: We found several genotypes associated with complete cytogenetic response: IFNG (rs1861494, rs2069705), FASL (rs763110), FAS (rs2234767, rs2234978), VEGFR2 (rs1531289), and WT1 (rs2234590); with major molecular response: IFNG (rs1861494, rs2069705), BIRC5 (rs9904341), FAS (rs2234978), and ABCG2 (rs2231142); with loss of response: IFNG (rs2069705), IFNGR2 (rs9808753), BIRC5 (rs9904341), and ORM (rs3182041); and with treatment failure: IFNG (rs2069705), JAK3 (rs3212713), and ORM (rs3182041). External validation for the above significant genotypes confirmed that the IFNG genotype (rs2069705) was predictive of complete cytogenetic response (hazard ratio, 2.17; P < 0.001) and major molecular response (hazard ratio, 1.96; P = 0.0001) in validation cohorts of Korean ethnicity. CONCLUSIONS: The IFNG genotype was predictive for response to imatinib therapy, suggesting potential involvement of the IFN-? signaling pathway in the mechanism of action of imatinib in CML. Clin Cancer Res; 16(21); 5339-50. ©2010 AACR.
PMID: 20959405 [PubMed - as supplied by publisher]
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Posted by rob on October 21, 2010 under Uncategorized |
Safety and efficacy of azacitidine in myelodysplastic syndromes.
Drug Des Devel Ther. 2010;4:221-9
Authors: Vigil CE, Martin-Santos T, Garcia-Manero G
PURPOSE: The clinical efficacy, different dosages, treatment schedules, and safety of azacitidine are reviewed. SUMMARY: Azacitidine is the first drug FDA-approved for the treatment of myelodysplastic syndromes that has demonstrated improvements in overall survival and delaying time to progression to acute myelogenous leukemia. The recommended dosage of azacitidine is 75 mg/m(2) daily for 7 days, with different treatment schedules validated. It appears to be well tolerated, with the most common adverse effects being myelosuppression. Several other off-label recommendations were also analyzed. CONCLUSION: Azacitidine is the first DNA hypomethylating agent approved by FDA for the treatment of myelodysplastic syndromes with demonstrated efficacy.
PMID: 20957213 [PubMed - in process]
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Posted by rob on October 20, 2010 under Uncategorized |
Phase 1 Study of sorafenib in patients with refractory or relapsed acute leukemias.
Haematologica. 2010 Oct 15;
Authors: Borthakur G, Kantarjian H, Ravandi F, Zhang W, Konopleva M, Wright JJ, Faderl S, Verstovsek S, Mathews S, Andreeff M, Cortes J
Background. Sorafenib is a multi- kinase inhibitor with activity against fms-like tyrosine kinase 3 with internal tandem duplication mutation and Raf kinase among others. A phase 1 dose escalation study of sorafenib was conducted in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias. Design and Methods. Fifty patients received one of two different schedules: Schedule “A”: Once or twice daily, 5 days per week, every week for a 21 day cycle; and Schedule”B”: Once or twice daily, for 14 days every 21 days. Dose limiting toxicities were grade 3/4 hypertension, hyperbilirubinemia, and amylase elevation. The recommended phase 2 dose in hematologic malignancies is 400 mg twice daily for both schedules. Results. Complete remissions or complete remissions with incomplete recovery of platelets were achieved in 5 (10%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Significant reduction in bone marrow and/or peripheral blood blasts was seen in an additional 17 (34%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Eleven of these responses (including 3 complete remissions /complete remissions with incomplete recovery) lasted for 2 cycles or beyond. In conclusion, sorafenib is active and well tolerated in acute myelogenous leukemia with fms-like tyrosine kinase 3 internal tandem duplication mutation. Conclusions. Additional studies of sorafenib in patients with acute myelogenous leukemia, particularly those with fms-like tyrosine kinase 3 internal tandem duplication, are warranted, including sorafenib-based combinations.Clinical Trial Registration Information: ClinicalTrials.gov Identifier: NCT00217646.
PMID: 20952518 [PubMed - as supplied by publisher]
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p57Kip2 is a downstream effector of BCR-ABL kinase inhibitors in chronic myelogenous leukemia cells.
Carcinogenesis. 2010 Oct 15;
Authors: Borriello A, Caldarelli I, Bencivenga D, Cucciolla V, Oliva A, Usala E, Danise P, Ronzoni L, Perrotta S, Della Ragione F
Chronic myelogenous leukemia (CML) is characterized by the expression of BCR-ABL tyrosine kinase, which results in increased cell proliferation and inhibition of apoptosis. In this study, we show that BCR-ABL positive CML cell lines treated with imatinib (STI571) undergo G1 cell cycle arrest associated with the accumulation of p57(Kip2), a cyclin-dependent kinase inhibitor (CKI). Interestingly, p57(Kip2) increase precedes the reported STI571-dependent up-regulation of p27(Kip1). A number of complementary approaches allow the demonstration that p57(Kip2) build-up is due to the transcriptional activation of CDKN1C, the p57(Kip2)-encoding gene, while neither p57(Kip2) half-life elongation nor its cell relocalization were observed. We also identified a heretofore undescribed pattern of p57(Kip2) phosphorylated isoforms which, however, did not change in response to STI571 cell treatment. The imatinib-dependent p57(Kip2) up-regulation occurs only in STI571-responsive cells, while the CKI accumulation was not evidenced in an imatinib-resistant clone. Nilotinib and dasatinib (second-generation BCR-ABL inhibitors), at concentrations comparable to those used in therapy, increase the CKI but do not affect p27(Kip1) level. Finally, CD34(+) cells from CML patients display a clear imatinib-dependent p57(Kip2) up-regulation, which was not observed in CD34(+) cells from control subjects. In conclusion, our study points to p57(Kip2) as a novel and precocious effector of BCR-ABL targeting drugs.
PMID: 20952511 [PubMed - as supplied by publisher]
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Can grapefruit juice decrease the cost of imatinib for the treatment of chronic myelogenous leukemia?
Leuk Res. 2010 Oct 15;
Authors: Kimura SI, Kako S, Wada H, Sakamoto K, Ashizawa M, Sato M, Terasako K, Kikuchi M, Nakasone H, Okuda S, Yamazaki R, Oshima K, Nishida J, Watanabe T, Kanda Y
PMID: 20952061 [PubMed - as supplied by publisher]
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Chronic myelogenous leukemia cells convert to myofibroblasts in vitro: Effect of vascular endothelial growth factor on development of the microenvironment.
Leuk Res. 2010 Oct 15;
Authors: Shirasaki R, Tashiro H, Mizutani-Noguchi M, Kawasugi K, Shirafuji N
To elucidate the biological characteristics of chronic myelogenous leukemia (CML) cells, we observed morphological and functional changes of CML cells during primary long-term culture, in which their morphology changed to that of myofibroblasts with similar molecular characteristics to the parental CML cells including BCR-ABL fusion gene, and produced cytokines such as granulocyte colony-stimulating factor, interleukin-6, and vascular endothelial growth factor (VEGF)-A. When cultured on the CML-derived myofibroblasts, parental non-adherent CML cells significantly proliferated. When anti-VEGF-A-neutralizing antibody was added to the cultures, non-adherent CML cell proliferation was significantly inhibited. These observations indicate that CML cells can convert their morphology and function to adherent myofibroblasts, and produce a significant amount of cytokine to give a growth-promotion activity to CML cells.
PMID: 20952060 [PubMed - as supplied by publisher]
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The Nationwide Austrian Aspergillus Registry: a prospective data collection on epidemiology, therapy and outcome of invasive mould infections in immunocompromised and/or immunosuppressed patients.
Int J Antimicrob Agents. 2010 Oct 12;
Authors: Perkhofer S, Lass-Flörl C, Hell M, Russ G, Krause R, Hönigl M, Geltner C, Auberger J, Gastl G, Mitterbauer M, Willinger B, Knöbl P, Resch G, Waldner R, Makrai A, Hartmann G, Girschikofsky M, Greil R
A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ?7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P>0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.
PMID: 20947312 [PubMed - as supplied by publisher]
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Dasatinib in imatinib-resistant or imatinib-intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily.
Cancer. 2010 Aug 15;116(16):3852-61
Authors: Saglio G, Hochhaus A, Goh YT, Masszi T, Pasquini R, Maloisel F, Erben P, Cortes J, Paquette R, Bradley-Garelik MB, Zhu C, Dombret H
BACKGROUND: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS: In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML.
PMID: 20564086 [PubMed - indexed for MEDLINE]
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Delivery of therapeutic shRNA and siRNA by Tat fusion peptide targeting BCR-ABL fusion gene in Chronic Myeloid Leukemia cells.
J Control Release. 2010 Aug 3;145(3):272-80
Authors: Arthanari Y, Pluen A, Rajendran R, Aojula H, Demonacos C
Gene silencing by RNA interference (RNAi) is a promising therapeutic approach for a wide variety of diseases for which the biological cause is known. The main challenge remains the ineffective RNAi delivery inside the cells. Non-viral gene delivery vectors have low immunogenicity compared to viral vectors, but are constrained by their reduced transfection efficiency. Silencing of the bcr-abl gene expression by RNAi confers therapeutic potential in Chronic Myeloid Leukemia (CML), but is limited by the cytotoxicity of the existing delivery methods. Here, we present evidence that the fusion between the cell penetrating peptide (CPP) HIV-Tat (49-57) and the membrane lytic peptide (LK15), Tat-LK15, mediates high transfection efficiency in delivering short hairpin RNA (shRNA) and small interfering RNA (siRNA) targeting the BCR-ABL oncoprotein in K562 CML cells. Our results show that shRNA complexes induce a more stable gene silencing of bcr-abl when compared to silencing mediated by siRNA complexes. In addition, silencing of the BCR-ABL oncoprotein by both shRNA and siRNA delivered by Tat-LK15 is more efficient and longer lasting than that achieved using Lipofectamine and more importantly without considerable cytotoxicity. In these terms Tat-LK15 can be an alternative to DNA/siRNA delivery in difficult-to-transfect leukemic cells.
PMID: 20403398 [PubMed - indexed for MEDLINE]
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Posted by rob on under Uncategorized |
Interferon regulatory factor 4 (IRF-4) plays important functions in B- and T-cell development and immune response regulation and was originally identified as the product of a proto-oncogene involved in chromosomal translocations in multiple myeloma. Although IRF-4 is expressed in myeloid cells, its function in that lineage is not known. The closely related family member IRF-8 is a critical regulator of myelopoiesis, which when deleted in mice results in a syndrome highly similar to human chronic myelogenous leukemia. In early lymphoid development, we have shown previously that IRF-4 and IRF-8 can function redundantly. We therefore investigated the effects of a combined loss of IRF-4 and IRF-8 on hematologic tumorigenesis. We found that mice deficient in both IRF-4 and IRF-8 develop from a …
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Posted by rob on October 17, 2010 under Uncategorized |
Interferon regulatory factor 4 (IRF-4) plays important functions in B- and T-cell development and immune response regulation and was originally identified as the product of a proto-oncogene involved in chromosomal translocations in multiple myeloma. Although IRF-4 is expressed in myeloid cells, its function in that lineage is not known. The closely related family member IRF-8 is a critical regulator of myelopoiesis, which when deleted in mice results in a syndrome highly similar to human chronic myelogenous leukemia. In early lymphoid development, we have shown previously that IRF-4 and IRF-8 can function redundantly. We therefore investigated the effects of a combined loss of IRF-4 and IRF-8 on hematologic tumorigenesis. We found that mice deficient in both IRF-4 and IRF-8 develop from a …
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Posted by rob on October 15, 2010 under Uncategorized |
Benzene and human health: A historical review and appraisal of associations with various diseases.
Crit Rev Toxicol. 2010 Nov;40(S2):1-46
Authors: Galbraith D, Gross SA, Paustenbach D
Over the last century, benzene has been a well-studied chemical, with some acute and chronic exposures being directly associated with observed hematologic effects in humans and animals. Chronic heavy exposures to benzene have also been associated with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) in humans. Other disease processes have also been studied, but have generally not been supported by epidemiologic studies of workers using benzene in the workplace. Within occupational cohorts with large populations and very low airborne benzene exposures (less than 0.1–1.0 ppm), it can be difficult to separate background disease incidence from those occurring due to occupational exposures. In the last few decades, some scientists and physicians have suggested that chronic exposures to various airborne concentrations of benzene may increase the risk of developing non-Hodgkin’s lymphoma (NHL) ( Savitz and Andrews, 1997 , Am J Ind Med 31:287–295; Smith et al., 2007 , Cancer Epidemiol Biomarkers Prev 16:385–391), multiple myeloma (MM) ( Goldstein, 1990 , Ann NY Acad Sci 609:225–230; Infante, 2006 , Ann NY Acad Sci 1076:90–109), and various other hematopoietic disorders. We present a state-of-the-science review of the medical and regulatory aspects regarding the hazards of occupational exposure to benzene. We also review the available scientific and medical evidence relating to benzene and the risk of developing various disorders following specific levels of exposure. Our evaluation indicates that the only malignant hematopoietic disease that has been clearly linked to benzene exposure is AML. Information from the recent “Benzene 2009,” a symposium of international experts focusing on the health effects and mechanisms of toxicity of benzene, hosted by the Technical University of Munich, has been incorporated and referenced.
PMID: 20939751 [PubMed - as supplied by publisher]
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Posted by rob on October 13, 2010 under Uncategorized |
[ABL1, SRC and other non-receptor protein tyrosine kinases as new targets for specific anticancer therapy]
Klin Onkol. 2010;23(4):203-9
Authors: Klener P, Klener P
Non-receptor protein tyrosine kinases are responsible for signal transduction during many physiologic cellular processes, including cell growth and proliferation, apoptosis, differentiation, regulation of actin cytoskeleton, cell shape, adhesion, motility and migration. Aberrant activity of protein tyrosine kinases (acquired as a result of chromosomal translocation or point mutation) has been implicated in the stimulation of cancer growth and progression, the induction of drug-resistance, tumour neovascularization, tissue invasion, extravasation and the formation of metastases. Small molecule tyrosine kinase inhibitors interfere with these pathophysiological circuits by blocking the signalling cascades triggered by the aberrantly activated protein tyrosine kinases (e.g. BCR-ABL1, FIP1L1-PDGFRA or ETV6-PDGFRB).Tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib) now belong to established anti-cancer agents with clinical activity in patients with CML, Ph+ ALL, and myeloid neoplasms with overexpression of PDGFRA, PDGFRB and wild-type KIT. New generation tyrosine kinase inhibitors (e.g. dasatinib) with extended activity against SRC and EPH kinases belong to promising anti-cancer agents with documented preclinical activity in several solid tumours (e.g. prostate cancer).
PMID: 20806817 [PubMed - indexed for MEDLINE]
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Tumor cell contamination in ovarian tissue cryopreserved before gonadotoxic treatment: should we systematically exclude ovarian autograft in a cancer survivor?
Bone Marrow Transplant. 2010 Jul;45(7):1247-8
Authors: Courbiere B, Prebet T, Mozziconacci MJ, Metzler-Guillemain C, Saias-Magnan J, Gamerre M
PMID: 19915633 [PubMed - indexed for MEDLINE]
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Posted by rob on October 12, 2010 under Uncategorized |
Early lymphocyte recovery following intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.
Blood. 2010 Oct 8;
Authors: Kanakry CG, Hess AD, Gocke CD, Thoburn C, Meyer C, Briel J, Luznik L, Smith BD, Levitsky H, Karp JE
Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery and attendant cytokine profiles in twenty consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4+ and included a greatly expanded population of CD3+CD4+CD25+Foxp3+ T cells. Recovering CD3+CD4+CD25+Foxp3+ T cells were phenotypically activated regulatory T cells and demonstrated suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells demonstrated marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by the majority of newly diagnosed AML patients after induction timed sequential chemotherapy. A better understanding of this oligoclonal regulatory T cell population will be fundamental towards developing effective immunomodulatory techniques to improve survival for patients with AML.
PMID: 20935254 [PubMed - as supplied by publisher]
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Allosteric inhibition of BCR-ABL.
Cell Cycle. 2010 Sep 3;9(18)
Authors: Hassan AQ, Sharma SV, Warmuth M
Impaired regulation of kinase activity can lead to a variety of diseases, including cancer. Inhibition of kinase activity has, therefore, been considered an attractive anti-cancer therapeutic strategy. The success of targeted therapy with kinase inhibitors has been well documented with BCR-ABL, where imatinib specifically inhibits kinase activity with impressive pharmacological responses in chronic myelogenous leukemia (CML). However, the success of kinase inhibitors as cancer therapeutics is being challenged clinically by the emergence of acquired resistance. Most kinase inhibitors available today are ATP-competitive. There have been efforts to develop kinase inhibitors with new modes of action. In this review, we highlight the development of ‘allosteric kinase inhibitors’ that inhibit kinase activity by binding to a site remote from the active site of the kinase. We focus on recent efforts directed towards BCR-ABL, for which, significant progress has been made to develop allosteric inhibitors with promising therapeutic activity, especially in the context of overcoming clinically acquired resistance mutations to the first generation of ATP-competitive kinase inhibitors.
PMID: 20930519 [PubMed - as supplied by publisher]
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Decitabine in myelodysplastic syndromes and chronic myelomonocytic leukemia: Argentinian/South Korean multi-institutional clinical experience.
Leuk Lymphoma. 2010 Oct 7;
Authors: Iastrebner M, Jang JH, Nucifora E, Kim K, Sackmann F, Kim DH, Orlando S, Jung CW, Basquiera A, Klein G, Santini F, Bernard HI, Korin J, Taborda G
This multicenter, open-label study evaluated the efficacy and safety of decitabine in patients from Argentina and South Korea with myelodysplastic syndromes or chronic myelomonocytic leukemia. Of 106 patients who received decitabine 20 mg/m<sup>2</sup> intravenously over 1 h once daily for 5 days in 4-week cycles, 99 patients were evaluable after receiving at least two cycles. The overall improvement rate was 35% (19% complete response +4% marrow complete response +4% partial response +8% hematologic improvement). Overall survival at 2 years was 71%. Treatment-related adverse events included febrile neutropenia, thrombocytopenia and bleeding, asthenia, fatigue, and eosinophilia. After complete response (CR), three patients received an allogeneic stem cell transplant. Four patients who relapsed after CR responded to decitabine retreatment. Acute myelogenous leukemia developed during follow-up in 21% of patients. Decitabine in a 5-day outpatient administration schedule was effective and well tolerated in typical clinical practice settings in South America and Asia.
PMID: 20929328 [PubMed - as supplied by publisher]
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Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia.
J Hematol Oncol. 2010 Oct 6;3(1):36
Authors: Pidala J, Kim J, Anasetti C, Kharfan-Dabaja MA, Nishihori T, Field T, Perkins J, Perez L, Fernandez HF
ABSTRACT: Optimal conditioning therapy for hematopoietic cell transplantation (HCT) in acute myelogenous leukemia (AML) remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1mg/kg every 6 hours for 4 days) and cyclophosphamide (60mg/kg IV x 2 days) – (Bu/Cy) with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC < 6000uM/L*min per day x 4 days) and fludarabine (40mg/m2 x 4 days) – (t-IV Bu/Flu). The Bu/Cy and t-IV Bu/Flu groups significantly differed according to donor relation, stem cell source, aGVHD prophylaxis, remission status, primary vs. secondary disease, median age, and % blasts prior to HCT (p < 0.01 for each). Conditioning with t-IV Bu/Flu reduced early toxicity including idiopathic pneumonia syndrome (IPS) and hepatic veno-occlusive disease (VOD). Additionally, the trajectory of early NRM (100 day: 16% vs. 3%, and1 year: 25% vs. 15% for Bu/Cy and t-IV Bu/Flu, respectively) favored t-IV Bu/Flu. Grade II-IV aGVHD (48% vs. 82%, p < 0.0001), as well as moderate/severe cGVHD (7% vs. 40%, p < 0.0001) differed between the Bu/Cy and t-IV Bu/Flu groups, due to the predominance of peripheral blood stem cells in the t-IV Bu/Flu group. Pharmacokinetic targeting of intravenous busulfan in combination with fludarabine is associated with reduced conditioning regimen related toxicity compared to oral busulfan and cyclophosphamide. However, multivariable analysis did not demonstrate significant differences in overall survival (p = 0.78) or non-relapse mortality (p = 0.6) according to conditioning regimen delivered.
PMID: 20925957 [PubMed - as supplied by publisher]
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Blast phase of chronic myeloid leukemia presenting lymphoid phenotype with a chronic phase of extremely short duration.
Intern Med. 2010;49(13):1297-301
Authors: Sumimoto H, Tsujimura H, Ise M, Mimura N, Sakai C, Takagi T, Kumagai K
Chronic myeloid leukemia (CML) is generally diagnosed in the chronic phase. We have recently encountered two CML-blastic phase (BP) cases, a 71-year-old woman and a 74-year-old man, who resembled de novo acute leukemia. The complete blood count was normal at least 11 and 13 months before the presentation, respectively. The leukemic cells showed predominant lymphoid phenotype. The blasts and granulocytes were positive for BCR-ABL, indicative of CML-BP. Both patients were successfully treated with prednisone and vincristine, followed by Imatinib. Our cases indicate rare presentations of CML-BP with an extremely short chronic phase. Ph-positive de novo acute leukemia should be carefully distinguished from CML-BP.
PMID: 20606363 [PubMed - indexed for MEDLINE]
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Graft-versus-host driven graft-versus-leukemia effect of minor histocompatibility antigen HA-1 in chronic myeloid leukemia patients.
Leukemia. 2010 Jul;24(7):1388-92
Authors: Mutis T, Brand R, Gallardo D, van Biezen A, Niederwieser D, Goulmy E, ,
PMID: 20508613 [PubMed - indexed for MEDLINE]
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