Favourable effect of the combination of acute and chronic graft-versus-host disease on the outcome of allogeneic peripheral blood stem cell transplantation for advanced haematological malignancies.

To assess the influence of graft-versus-host disease (GVHD) on the outcome of patients with advanced haematological malignancies (AHM) who received a primary, unmodified allogeneic peripheral blood progenitor cells transplant (allo-PBT) from a human leucocyte antigen (HLA) identical sibling donor, we analysed 136 patients with myeloid neoplasms (n = 70) or lymphoproliferative disorders (n = 66), transplanted at 19 Spanish institutions. Median age was 35 years (range 1-61). The cumulative incidence of relapse for all patients was 34% (95% CI, 26-42%), 41% (95% CI, 33-49) for patients without GVHD and 14% (95% CI, 3-25) (P = 0.

[The retinoic acid syndrome, a complication of acute promyelocytic leukemia therapy].

Objective: To describe the retinoic acid syndrome, a complication of therapy with all-trans retinoic acid (ATRA) in acute promyelocitic leukemia (APL).

Patients And Methods: Retrospective study of five patients with a morphologic diagnosis of APL by the French-American-British (FAB) classification that were treated for remission induction with ATRA and developed the ATRA syndrome.

Results: Three patients in newly diagnosed APL and two in leukemia relapse were analyzed.

Time-resolved spatial profile of TEA CO2 laser pulses: influence of the gas mixture and intracavity apertures.

The evolution of the intensity profile of transversely excited atmospheric CO2 laser pulses is investigated within the intensity moment formalism. The beam quality factor M2 is used to study the mode evolution. Attention is focused on the influence of both the gas mixture (N2 :CO2 :He) and the diameter of an intracavity diaphragm placed to attenuate higher-order modes.

Complete spatial characterization of a pulsed doughnut-type beam by use of spherical optics and a cylindrical lens.

A complete spatial characterization (in second-order moments) of a doughnut-type beam from a pulsed transversely excited atmospheric CO2 laser is described. It includes the measurement of the orbital angular momentum carried by the beam. The key element in the characterization is the use of a cylindrical lens in addition to the usual spherical optics.

Donor age-related differences in PBPC mobilization with rHuG-CSF.

Background: Data on the administration of rHuG-CSF to normal donors <18 years old are very limited.

Study Design And Methods: The results of rHuG-CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors > or = 18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.

Autologous stem-cell transplantation for Hodgkin's disease: results and prognostic factors in 494 patients from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group.

Purpose: To analyze clinical outcome and significant prognostic factors for overall (OS) and time to treatment failure (TTF) in a group of 494 patients with Hodgkin's disease (HD) undergoing autologous stem-cell transplantation (ASCT).

Patients And Methods: Detailed records from the Grupo Español de Linfomas/Transplante Autólogo de Médula Osea Spanish Cooperative Group Database on 494 HD patients who received an ASCT between January 1984 and May 1998 were reviewed. Two hundred ninety-eight males and 196 females with a median age of 27 years (range, 1 to 63 years) received autografts while in complete remission (n = 203) or when they had sensitive disease (n = 206) or resistant disease (n = 75) at a median time of 26 months (range, 4 to 259 months) after diagnosis.

Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients.

We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50-90% reduction).

Conditioning regimens in autologous stem cell transplantation for multiple myeloma: a comparative study of efficacy and toxicity from the Spanish Registry for Transplantation in Multiple Myeloma.

High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m2 melphalan (MEL200), 127 patients with 140 mg/m2 melphalan plus total body irradiation (MEL140 + TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL).

In vivo regulation of cell death by embryonic (pro)insulin and the insulin receptor during early retinal neurogenesis.

Programmed cell death is an established developmental process in the nervous system. Whereas the regulation and the developmental role of neuronal cell death have been widely demonstrated, the relevance of cell death during early neurogenesis, the cells affected and the identity of regulatory local growth factors remain poorly characterized. We have previously described specific in vivo patterns of apoptosis during early retinal neurogenesis, and that exogenous insulin acts as survival factor (Díaz, B.

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry. Spanish Group of Allo-PBT.

A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively.

Iron depletion by phlebotomy with recombinant erythropoietin prior to allogeneic transplantation to prevent liver toxicity.

Iron overload may induce liver toxicity after hematopoietic stem cell transplantation (HSCT), but it is not known if iron depletion prior to HSCT can reduce the risk of severe toxicity in this setting. We used subcutaneous recombinant erythropoietin (EPO) (25 UI/kg) three times a week and phlebotomy once a week, to prevent liver toxicity in a patient with advanced acute leukemia and liver disease due to severe iron overload, previous drug toxicity and hepatitis C viral infection. Over the 9 months prior to allogeneic HSCT, 34 phlebotomies were carried out.

(Pro)insulin and insulin-like growth factor I complementary expression and roles in early development.

Evidence that the insulin-like growth factors play a role in embryonic as well as postnatal growth and central nervous system development has accumulated recently from studies using knock-out mice models. However, no effects of IGF-I and II have been demonstrated prior to organogenesis in these studies. We summarize here results supporting the role of insulin (or its precursor proinsulin) in vertebrate development prior to the expression of IGFs.

Synthesis and differentially regulated processing of proinsulin in developing chick pancreas, liver and neuroretina.

Regulated preproinsulin gene expression in nonpancreatic tissues during development has been demonstrated in rodents, Xenopus and chicken. Little is known, however, about the synthesis and processing of the primary protein product, proinsulin, in comparison with these events in pancreas. Using specific antisera and immunocytochemistry, immunoblot and HPLC criteria, we characterize the differential processing of proinsulin in developing neuroretina, liver and pancreas.

Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group.

All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL.

Modulation of the chaperone heat shock cognate 70 by embryonic (pro)insulin correlates with prevention of apoptosis.

Insights have emerged concerning insulin function during development, from the finding that apoptosis during chicken embryo neurulation is prevented by prepancreatic (pro)insulin. While characterizing the molecules involved in this survival effect of insulin, we found insulin-dependent regulation of the molecular chaperone heat shock cognate 70 kDa (Hsc70), whose cloning in chicken is reported here. This chaperone, generally considered constitutively expressed, showed regulation of its mRNA and protein levels in unstressed embryos during early development.

Autologous peripheral blood stem cell transplantation for multiple myeloma: a report of 259 cases from the Spanish Registry. Spanish Registry for Transplant in MM (Grupo Español de Trasplante Hematopoyético-GETH) and PETHEMA.

Between January 1989 and November 1995, 259 patients with multiple myeloma (MM), 22 stage I, 57 stage II and 180 stage III at diagnosis were treated with myeloablative high-dose therapy followed by autologous peripheral blood stem cell (PBSC) transplantation. The median time from diagnosis to transplantation was 17 months (6-112). At the time of transplant, 56 patients were in CR, 153 in PR, 25 were nonresponders and 25 had progressive disease.

Role of prepancreatic (pro)insulin and the insulin receptor in prevention of embryonic apoptosis.

The characterization of (pro)insulin as an early embryonic growth factor requires demonstration of its expression and cellular effects in vivo. By in situ hybridization, we found widespread preproinsulin transcripts in the chick embryo throughout gastrulation and neurulation, before the beginning of preproinsulin-like growth factor I expression and pancreatic organogenesis. To analyze the prepancreatic (pro)insulin effect on apoptotic cell death, we treated embryos with antisense oligodeoxynucleotides in ovo and in vitro.

The use of an expanded circulating hematopoietic progenitor cell pool associated with bone marrow fibrosis for the support of autologous transplantation in IgD multiple myeloma.

Leukoerythroblastosis and myelofibrosis were observed at presentation in a patient with IgD myeloma. Interestingly, a 1000-fold increase in peripheral blood progenitor cells (PBPC) was found in the steady state without signs of any underlying myeloproliferative disorder. The myeloma was resistant to conventional therapy.

Idarubicin and intermediate dose ARA-C followed by consolidation chemotherapy or bone marrow transplantation in relapsed or refractory acute myeloid leukemia.

Sixty-one adult patients with relapsed or refractory acute myelogenous leukemia (AML) were treated in a cooperative study with Idarubicin 12 mg/m2/day on days 1 to 3 and AraC 1 g/m2/12h on days 1 to 4. Responding patients were scheduled for consolidation with Ida-IDAraC and bone marrow transplantation (BMT) when feasible. Twelve of 23 refractory patients (52%) and 21 of 38 relapsed patients (55%) achieved complete remission (CR).

Invasive Helicobacter-like organisms in feline gastric mucosa.

Background: Helicobacter-like organisms (HLOs) usually are present in the stomachs of cats. Although the histopathology of natural (H. felis or H.

Differential and tissue-specific regulation of (pro)insulin and insulin-like growth factor-I mRNAs and levels of thyroid hormones in growth-retarded embryos.

The control of embryonic growth in vertebrates appears to rely on the orchestrated action of several families of growth factors and hormones. The contribution of insulin-like growth factor (IGF-I) to prenatal growth regulation is better established in mammals than in other vertebrate species. The status of (pro)insulin gene product(s) in the pancreas and non-pancreatic tissues may be another important contribution to embryonic growth signals.