[Hairy cell leukemia in pregnancy]. / Bialaczka wlochatokomórkowa u kobiety w ciazy.

Pregnancy complicated by HCL is an extremlely rare event: only 5 report of HCL in pregnancy have been previously described. A 36-year-old women was diagnosed of HCL presented in 14 week of her 5th pregnancy. Therapy was initiated in 18 wk of gestation with IFN-alpha at dose 6 x 106 U subcutaneous 3 times per week and prednisone 20 mg/d. IFN-alpha administration was well tolerated. After IFN-alpha therapy partial remission was achieved. The course of the pregnancy was normal. At week 39 of gestation a cesarean cection was performed and the patient delivered a healthy male infant weighing 3460 g with Apgar score of 10. The placenta was of normal size, no infiltration of hairy cell was founded. Post-partum course was uncomplicated. The patient elected to not breast feed her infant. 3 weeks after delivery patient had a 5-days course of 2CDA

G-CSF administered in time-sequenced setting during remission induction and consolidation therapy of adult acute lymphoblastic leukemia has beneficial influence on early recovery and possibly improves long-term outcome: a randomized multicenter study.

Sixty-four untreated adult acute lymphoblastic leukemia (ALL) patients were randomized to receive chemotherapy alone, n = 31 or chemotherapy and granulocyte colony stimulating factor (G-CSF), n = 33. During induction patients received G-CSF for 5 days between four weekly Epirubicin+Vcr administrations, starting 36 h after each application and finishing 48 h before the next one with the intention to possibly generate a cell cycle dependent protection of normal hematopoietic progenitors and to stimulate granulopoiesis. The complete remission (CR) rate equaled 94% in the G-CSF group and 87% in controls. Patients who received G-CSF, if compared to the controls, had shorter granulocytopenia during induction and consolidation, displayed a lower infection rate, completed the induction-consolidation quicker and stayed shorter in hospital during induction, p < 0.001-0.04. Follow-up at 2 years revealed a rather higher probability of survival (59 vs. 27%, p = 0.04) and a lower relapse rate (32 vs. 60%) in G-CSF arm than in controls. The beneficial influence of G-CSF administered in time-sequenced fashion on survival needs further confirmation.

Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience).

Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.

A prospective study of the incidence of agranulocytosis and aplastic anemia associated with the oral use of metamizole sodium in Poland.

BACKGROUND: Metamizole is a common analgesic and antipyretic drug. However, its use has been associated with a risk of side-effects involving agranulocytosis and aplastic anemia. These reactions are rare and unpredictable. The aim of this prospective study was to evaluate the risks of these complications in Poland, where this medication is available without prescription. MATERIAL/METHODS: Six hematological centers, serving approximately 40% (ca. 15 million people) of the country's population, participated in the study. All cases of agranulocytosis and aplastic anemia were recorded and their severity and association with the use of drugs, especially metamizole sodium, were evaluated. All the patients receiving cytostatic or immunosuppressive drugs were excluded. RESULTS: During the 12 months of the study, 2 cases of aplastic anemia and no cases of agranulocytosis were confirmed which may have been associated with the use of metamizole. Overall, we recorded 16 cases of agranulocytosis and 27 cases of aplastic anemia. The two cases of metamizole sodium-induced aplastic anemia were non-fatal in character. CONCLUSIONS: Considering the consumption of 112,300,094 tablets of metamizole in Poland a year, the figures obtained result in an incidence of 0.25 cases of aplastic anemia per 1 million persons per day of treatment; this value being less than that for other nonsteroidal anti-inflammatory drugs. Nevertheless, caution is recommended in the application of metamizole, particularly over long periods and in large doses.

Ceramides and glycosphingolipids in maturation process: leukemic cells as an experimental model.

Leukemic cells were used as experimental material to demonstrate changes in the content of GSLs during the development and maturation of neutrophils. The most abundant cellular GSL is LacCer. An elevation in the LacCer level occurs twice during the maturation process: initially, on formation of azurophil granules, and subsequently, (a more significant rise) on formation of specific granules. The formation of the latter is accompanied by an increase in the level of GalGalCer. During the maturation of myeloblasts, there is a simultaneous growth in the content of LacCer and GM3 as well as that of their common precursors, that is, free ceramides. Like other tumor cells, GM3 rich myeloblasts in the peripheral blood from patients with AML are characterized by shedding of gangliosides. The quantitative Cer/GlcCer ratio in these cells seems to be advantageous for the efficacy of chemotherapy in the induction of apoptosis. Myelo- and metamyelocytes achieve the highest level of GSLs. Their entry into the full maturity stage is accompanied by a decrease in the level of GSLs. Patterns of GSLs expression change greatly during development and maturation. However, with respect to the composition and content of GSLs, there are no significant differences between normal and leukemic mature neutrophils. At each stage of the development and maturation of myelogenous leukemic cells, as well as in normal mature neutrophils, there occurs the synthesis of the same molecular species both free ceramides and ceramide portions of LacCer, precursor of more complex GSLs.