BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

OBJECTIVETo investigate the effectiveness and safety of domestically produced recombinant human interleukin 11 (rhIL-11) for the treatment of chemotherapy- induced thrombocytopenia.

METHODSA total of 32 solid cancer patients who developed chemotherapy-induced thrombocytopenia ( _70 x 10(9)/L) after the first cycle of chemotherapy was studied by self-cross control. The patients were given subcutaneous injection of rhIL-11 (25 microg x kg(-1) x d(-1)) for 7 to 14 consecutive days or until platelet count > or = 100 x 10(9)/L during the second cycle of chemotherapy using the identical regimen as in the first cycle.

RESULTSThe mean platelet count of the patients after rhIL-11 treatment was higher at different time points during the second cycle of chemotherapy than that during the first cycle of chemotherapy with the mean platelet count of (110.2 +/- 53.5) x 10(9)/L in the first cycle of chemotherapy versus (55.6 +/- 46.8) x 10(9)/L in the second cycle of chemotherapy (P < 0. 01). Patients with platelet count < or = 50 x 10(9)/L was 4/32 (12.5%) in the first cycle of chemotherapy and 12/32 (37.5%) in the second cycle of chemotherapy (P < 0.01). The time recovery to the normal platelet count was 2 - 18 days (median 5 days) in the first cycle of chemotherapy versus 5 - 27 days (median 12 days) in the second cycle of chemotherapy (P < 0.01). The case/frequency of the platelet transfusion was 2/2 in the first cycle of chemotherapy, while it was 7/9 in the second cycle of chemotherapy (P < 0.01). The major adverse reactions relative to rhIL-11 treatment were fatigue, myalgia/arthralgia, ache, headache, palpitation, edema and fever, most of which could be relieved automatically without any specific treament. However, some 3 grade side effects such as fatigue, myalgia/arthralgia and headache needed proper medication.

CONCLUSIONrhIL-11 is safe and effective for chemotherapy-induced thrombocytopenia with mild and manageable side effects.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; Fatigue ; chemically induced ; Female ; Humans ; Injections, Subcutaneous ; Interleukin-11 ; adverse effects ; genetics ; therapeutic use ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; Platelet Count ; Recombinant Proteins ; administration & dosage ; adverse effects ; therapeutic use ; Stomach Neoplasms ; drug therapy ; Thrombocytopenia ; chemically induced ; drug therapy ; Treatment Outcome

Imatinib mesylate has been commonly used in the treatment of patients with chronic myeloid leukemia (CML). However, a significant number of CML patients treated with imatinib developed thrombocytopenia. Platelet-derived growth factor (PDGF)/platelet-derived growth factor receptor (PDGFR) plays a significant role in the regulation of thrombopoiesis. It is suggested that imatinib may block the PDGF/PDGFR and PI3-K/Akt pathway, then inducing the apoptosis of megakaryocytes and developing thrombocytopenia in these patients. In this review, the potential molecular mechanism of imatinib-induced thrombocytopenia in the treatment of CML patients is discussed, including imatinib and thrombocytopenia, PDGF/PDGFR and thrombopoiesis, potential mechanism of imatinib-induced thrombocytopenia in treatment of patients with CML and so on.
Antineoplastic Agents ; adverse effects ; therapeutic use ; Benzamides ; Caspase 3 ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; metabolism ; Piperazines ; adverse effects ; therapeutic use ; Platelet-Derived Growth Factor ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Pyrimidines ; adverse effects ; therapeutic use ; Signal Transduction ; Thrombocytopenia ; chemically induced ; Thrombopoiesis