Blood
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Secondary neoplasms (SNs) represent serious late complications after successful treatment of malignant diseases. To evaluate the rate and type of SNs after Berlin-Frankfurt-Münster (BFM) treatment in children with acute lymphoblastic leukemia (ALL), we analyzed the data from the BFM database and the German Childhood Cancer Registry (GCCR). Between April 1979 and April 1995, 5006 children with B-precursor or T-ALL were enrolled in 5 ALL-BFM multicenter trials. ⋯ The development of secondary AML was not associated with the use of any specific cytotoxic agent. Considering the high-survival rate of this large unselected ALL cohort, the risk of SN is relatively low, though higher, especially after cranial irradiation, than in the general population. Long-term follow-up is mandatory, and further SNs with longer latency periods are to be expected. (Blood. 2000;95:2770-2775)
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The involvement of the cytokine signaling pathway in oncogenesis has long been postulated. Recently, rearrangements of the gene encoding the tyrosine Janus kinase 2 (JAK2) have been reported in human leukemias indicating a direct JAK-signal transduction and activator of transcription (STAT)-mediated leukemic process. The leukemia-associated TEL-JAK2 fusion protein is formed by the oligomerization domain of the translocated ets leukemia (TEL) protein fused to the catalytic domain of JAK2. ⋯ High levels of expression of the Stat5-target genes pim-1, osm, and Cis were observed in all the cytokine-independent cell lines. Furthermore, the expression of a dominant negative form of Stat5A markedly interfered with the growth factor independence process mediated by TEL-Jak2 in Ba/F3 cells. Because the BCR-ABL and TEL-PDGFbetaR oncoproteins also activate Stat5, activation of this factor should be a crucial step in activated tyrosine kinase-mediated leukemogenesis. (Blood. 2000;95:2076-2083)
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We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. ⋯ Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)
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Case Reports
Hypofibrinogenemia in an individual with 2 coding (gamma82 A-->G and Bbeta235 P-->L) and 2 noncoding mutations.
We investigated the molecular basis of hypofibrinogenemia in a man with a normal thrombin clotting time. Protein analysis indicated equal plasma expression of 2 different Bbeta alleles, and DNA sequencing confirmed heterozygosity for a new Bbeta235 P-->L mutation. Protein analysis also revealed a novel gamma(D) chain, present at a ratio of 1:2 relative to the gamma(A) chain. ⋯ This was supported by analysis of 31 normal controls in whom the Bbeta mutations were found at polymorphic levels, with an allelic frequency of 5% for the Bbeta235 mutation and 42% for the Bbeta 3' untranslated mutation. The gamma82 mutation was, however, unique to the propositus. Residue gamma82 is located in the triple helix that separates the E and D domains, and aberrant packing of the helices may explain the decreased fibrinogen concentration. (Blood. 2000;95:1709-1713)
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Comparative Study
Sickle cell anemia day hospital: an approach for the management of uncomplicated painful crises.
Painful crisis episodes are poorly treated in sickle cell anemia, both in timeliness and appropriateness of care. Delayed treatment in Emergency Departments, unrelieved pain, frequent admissions, and prolonged hospitalizations are common. We established a Day Hospital (DH) to determine if an alternative care delivery system could improve pain relief and reduce unnecessary hospital admissions for patients with uncomplicated painful crises. ⋯ The length of stay (LOS) for inpatients followed by the DH staff decreased by 1.5 days, while the LOS for patients followed by non-DH staff remained unchanged. Reduction of admissions and LOS represented a savings of approximately $1.7 million. We conclude that a dedicated facility provides the kingpin for effective and rapid painful crisis management, reduces hospitalizations, and facilitates integration of the approach into other areas of care. (Blood. 2000;95:1130-1136)