Possible fenugreek induced haemolysis in a patient with previously unknown G6PD deficiency.

Glucose 6 phosphate dehydrogenase (G6PD) deficiency is the most common disease producing enzymopathy. People with G6PD deficiency cannot cope with oxidative stressors. These patients are asymptomatic until they develop a haemolytic crisis which presents as anaemia and jaundice. The agents known to cause haemolysis in these patients are: oxidant drugs, (primaquine, chloroquine and other anti-malarials), antibiotics, (chloramphenicol, nitrofurantoin, sulphonamides, and all quinolone antibiotics). Chemicals to be avoided are moth balls (napththalene), aniline dyes, and some Chinese herbal medicine (San Chi, Chuan Lian). The classic presentation of exposure to Fava beans (legumes), causing oxidative haemolysis, has led G6PD deficiency to be also known as Favism. The patient we present here had no exposure to any of the known causes of oxidative haemolysis. Instead his precipitating cause strongly suggests raw fenugreek (T foenum-graecum L), a legume used as a herbal treatment for diabetes and previously not known to be a precipitant of haemolysis in G6PD deficiency.

Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia.

Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph(+)) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasa-tinib (a dual-specific SRC/BCR-ABL kinase inhibitor) were compared in a preclinical mouse model of intracranial Ph(+) leukemia. Clinical dasatinib treatment in patients with CNS Ph(+) leukemia was assessed. In preclinical studies, dasatinib increased survival, whereas imatinib failed to inhibit intracranial tumor growth. Stabilization and regression of CNS disease were achieved with continued dasa-tinib administration. The drug also demonstrated substantial activity in 11 adult and pediatric patients with CNS Ph(+) leukemia. Eleven evaluable patients had clinically significant, long-lasting responses, which were complete in 7 patients. In 3 additional patients, isolated CNS relapse occurred during dasatinib therapy; and in 2 of them, it was caused by expansion of a BCR-ABL-mutated dasatinib-resistant clone, implying selection pressure exerted by the compound in the CNS. Dasatinib has promising therapeutic potential in managing intracranial leukemic disease and substantial clinical activity in patients who experience CNS relapse while on imatinib therapy. This study is registered at ClinicalTrials.gov as CA180006 (#NCT00108719) and CA180015 (#NCT00110097).

Aberrant positivity for CD79a in erythroid lineage cells--a finding observed in a subset of re-staging bone marrow trephine biopsies after treatment cell pain.

Aberrant expression of CD79a has been reported in neoplastic cells in peripheral T cell lymphoma, T-cell acute lymphoblastic leukemia and acute myeloid leukemia (especially those with t(8;21)). In this report, we document the first report of CD79a positivity in erythroid precursor cells in bone marrow. In all, we document this finding in five of 18 re-staging bone marrow trephine samples in patients of lymphoma treated with chemotherapy (one index case and 17 additional validation cases). It is important to appreciate this finding especially in rituximab treated patients where one tends to rely on CD79a to identify minimal marrow disease.

Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia.

The FIP1L1-PDGFRA fusion gene is a recurrent molecular lesion in eosinophilia-associated myeloproliferative disorders, predicting a favorable response to imatinib mesylate. To investigate its prevalence, 376 patients with persistent unexplained hypereosinophilia were screened by the United Kingdom reference laboratory, revealing 40 positive cases (11%). To determine response kinetics following imatinib, real-time quantitative-polymerase chain reaction (RQ-PCR) assays were developed and evaluated in samples accrued from across the European LeukemiaNet. The FIP1L1-PDGFRA fusion transcript was detected at a sensitivity of 1 in 10(5) in serial dilution of the EOL-1 cell line. Normalized FIP1L1-PDGFRA transcript levels in patient samples prior to imatinib varied by almost 3 logs. Serial monitoring was undertaken in patients with a high level of FIP1L1-PDGFRA expression prior to initiation of imatinib (100 mg/d-400 mg/d). Overall, 11 of 11 evaluable patients achieved at least a 3-log reduction in FIP1L1-PDGFRA fusion transcripts relative to the pretreatment level within 12 months, with achievement of molecular remission in 9 of 11 (assay sensitivities 1 in 10(3)-10(5)). In 2 patients, withdrawal of imatinib was followed by a rapid rise in FIP1L1-PDGFRA transcript levels. Overall, these data are consistent with the exquisite sensitivity of the FIP1L1-PDGFRalpha fusion to imatinib, as compared with BCR-ABL, and underline the importance of RQ-PCR monitoring to guide management using molecularly targeted therapies.

Systemic capillary leak syndrome after granulocyte colony-stimulating factor (G-CSF).

Capillary leak syndrome (CLS) commonly occurs in the intensive care setting. CLS is seen in conditions such as septic shock or may result from conditions such as multitrauma and pancreatitis, which result in the systemic inflammatory response syndrome (SIRS). We present two cases in which both patients suffered with CLS, which we believe was caused following administration of granulocyte colony-stimulating factor, to our knowledge not described in the intensive care patient previously. We discuss how these patients management differs from other intensive care unit patients with CLS and how it is important to diagnose this condition early in haematological oncology cases.