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Biomedical subjects

J Sierra

Publications and source records attributed to J Sierra.

At least 145 records · Page 8Linked to original sources
PubMed1997

[Hemopoietic progenitor cell transplantation: 20 years' experience at the Hematology School "Farreras-Valentí"/Clinical Hospital of Barcelona].

BACKGROUND: Hemopoietic progenitor cell transplantation (HPCT) is acquiring an increasing role in the therapy for a variety of disorders. In this study, main characteristics and results of HPCT along 20 years are analyzed from the experience of Postgraduate School of Hematology "Farreras-Valentí" at the Hospital Clínic in Barcelona. PATIENTS AND METHODS: Six-hundred ninety-five patients transplanted between June 1976 and January 1996 were analyzed. Median age (range) were 33 (4-63) years. The following aspects were considered: donor type, source or progenitor cells, type of disease and disease-stage at transplantation, transplant related mortality and survival. RESULTS: A total of 714 HPCT were performed (448 allogeneic, 13 isogeneic, 253 autogeneic). Allogeneic HPCT were from an HLA-identical sibling in 408 cases, from other familial donors in 10, and from non-familial donors in 30. Most HPCT from non-familial donors (93%) were performed during the last five years of the study (1991-1995). The source of hemopoietic progenitor cells was bone marrow in 625 instances (88%), peripheral blood in 88 (12%), and fetal liver in one. During more than 15 years, the only source of progenitors was the bone marrow; in contrast, in the last 3 years (1993-1995) transplants using peripheral blood were predominant. Main indications for HPCT were the following: acute leukemias (n = 387) (54%), chronic leukemias (n = 134) (19%), severe aplastic anemia (n = 58) (8%), lymphomas (n = 80) (11%), multiple myeloma (n = 39) (5%) and myelodysplastic syndromes (n = 14) (2%). In patients with hematological malignancies (n = 656), HPCT was performed in first complete remission or in first chronic phase in 321 instances (49%), in subsequent remissions in 144 (22%), and in more advanced stages in the remaining 191 (29%). In the more recent years, a progressive decrease in the number of HPCT for acute leukemia or aplastic anemia was observed, contrasting with an increase in transplants for lymphoma, multiple myeloma and myelodysplastic syndromes. Of note, a significant decrease in transplant related mortality was evident along the years, both after autogeneic HPCT (21% during 1985-1992 and 6% thereafter) (p = 0.001) and after allogeneic transplantation (54%, 44%, and 20% during the periods 1976-1984, 1985-1992 and 1993-1995, respectively) (p = 0.004). The fact translated into an increase in the actuarial probability of survival after allogeneic HPCT (25%, 33% and 58% in the three mentioned periods, respectively) (p = 0.0003), and after autogeneic HPCT (33% in the interim 1985-1992, and 55% in the period 1993-1995) (p = 0.001). CONCLUSIONS: During the last 20 years, HPCT has significantly evolved in aspects such as type of donor, source of progenitor cells and indications. Remarkably, a progressive decrease in transplant related mortality has been observed translating into a improvement in survival after the procedure.

Actuarial Analysis↗
PubMed1997

Autologous stem cell transplantation for poor prognosis Hodgkin's disease in first complete remission: a retrospective study from the Spanish GEL-TAMO cooperative group.

Although more than 50% of Hodgkin's disease patients are cured with conventional chemotherapy, many will relapse and eventually die from their disease. Many efforts have been made to identify poor prognostic factors that could be useful in selecting high-risk patients in 1st CR who may benefit from high-dose chemo/radiotherapy. However, the role of early transplantation in 1st CR remains unclear. We have retrospectively analyzed the results obtained with this procedure in 22 hospitals belonging to the Spanish GEL/TAMO cooperative group. Twenty-seven patients, of whom 19 were males, underwent autologous transplantation for Hodgkin's disease in 1st CR between January 1987 and January 1996. Remission had been achieved after one (n = 22) or two (n = 5) lines of treatment. Twenty-four patients had advanced stage disease, 12 patients bulky mediastinal disease, nine bone marrow involvement and 18 had extranodal disease. Peripheral blood was used as the source of hematopoietic stem cells in 15 patients, BM in nine, and both in three. All but three patients received chemotherapy-based conditioning regimens (16 CBV, four BEAM and four BEAC), while three were conditioned with CY and TBI. There were no transplant-related deaths. Median (range) times to recover >0.5 x 10(9)/l neutrophils and >50 x 10(9)/l platelets were 14 (8-56) days and 16 (8-240) days, respectively. With a median follow-up of 30 (8-66) months, 21 patients are alive and in continuous CR. Four patients who relapsed after transplant at 8, 17.5, 22 and 26 months achieved a second CR with conventional chemotherapy; one patient relapsed 92 months post-transplant and died 5 months afterwards. Another patient died 30.5 months post-transplant from a secondary malignancy. In conclusion, high-dose therapy in poor prognosis Hodgkin's disease in 1st CR was well tolerated with no transplant-related mortalities. Although the follow-up of this series is relatively short, our results seem promising. Nevertheless, late relapses can occur, and the role of this procedure vs conventional treatment in very high-risk patients should be assessed in prospective randomized studies.

Adolescent↗
PubMed1997

Successful autografting in chronic myelogenous leukaemia using Philadelphia negative blood progenitor cells mobilized with rHuG-CSF alone in a patient responding to alpha-interferon.

Several non-randomized studies suggest a possible survival advantage for chronic myelogenous leukaemia (CML) patients treated with an autologous stem-cell transplantation. Due to the possible contribution of residual leukaemic cells present in the inoculum in post-transplant relapse, several methods are being evaluated to eliminate neoplastic cells or to select 'normal' (Ph1 negative) progenitor cells for autografting. Recently, several studies have shown that Ph1 negative blood progenitor cells can be mobilized by rHuG-CSF alone in patients who have a cytogenetic response to alpha-interferon (IFN). We describe the first case, as far as we are aware, of a CML patient responding to IFN autografted by using blood progenitor cells collected by rHuG-CSF alone.

Adolescent↗
PubMed1997

[Molecular genetic study in congenital myotonic dystrophy].

Congenital myotonic dystrophy (CMD) is the neonatal form of Steinert's myotonia. However, the symptoms and neuro-physiological findings are different from the classical adult form, there is a high mortality and early diagnosis of the condition is difficult. CMD occurs as a result of abnormal expansion of CTG triplets on chromosome 19. There is dominant autosomal transmission of this multi-systemic disorder, although when it occurs in children, it is the mother who is always the affected parent. Molecular genetic techniques enable unequivocal diagnosis of the condition, evaluation of anticipation and the possibility of offering genetic counselling to the families involved.

Chromosome Aberrations↗
PubMed1996

[Allogeneic transplant of peripheral blood hematopoietic progenitors. Preliminary experience].

Myeloablative treatment followed by allogeneic transplantation of peripheral blood hemopoietic progenitors (alloPBT) was administered to five leukemia patients with a high risk of relapse. The donors subcutaneously received 10 micrograms/kg/day of G-CSF for five days. The tolerance to this medication was good with only complaints of moderate bone pain. Two of the peripheral blood donors had previously been bone marrow donors and both expressed their preference for the new method. The product of peripheral blood leukapheresis contained from one to four-fold more hemopoietic progenitors and approximately ten-fold more T-lymphocytes than the bone marrow received from normal donors. Prophylaxis of the graft versus host disease (GVHD) consisted of cyclosporine A (CsA) in one case and CsA and methotrexate (MTX) in four cases. The bone marrow implantation was verified with a neutrophil count of up to more than 0.5 x 10(9)/l between days 12 to 21 after transplant and a platelet count higher than 20 x 10(9)/l from days 11 to 41 after transplant. Acute GVHD was clinical grade O (two cases), II (one case) and grade III (two cases). In conclusion, alloPBT may be more safely and comfortably performed to the donor. This method may provide rapid recovery of neutrophils and platelets in patients without an apparent increase in the risk of developing graft versus host disease.

Adolescent↗
PubMed1996

Study of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation using PCR amplification of short tandem repeats.

Allogeneic peripheral blood progenitor cell transplantation (PBPCT) is increasingly being used to treat hematologic malignancies. However, the capacity of PBPC to maintain long-term hematopoiesis remains controversial. To add further information to this issue we studied the chimeric status in 12 patients receiving G-CSF-mobilized PBPC from HLA-identical sibling donors. All patients were conditioned with cyclophosphamide and total body irradiation. In six cases the apheresis product was partially T-cell depleted by counterflow centrifugation (n = 2) or the immunoadsorption biotin-avidin method (n = 4). The follow-up was longer than 6 months in five patients, with a maximum of 420 days. Molecular analysis of the engraftment was done using PCR amplification of short tandem repeats. Apparent complete donor chimerism was detected in all patients between 28 and 420 days after engraftment. This study indicates that full short-term engraftment is achieved in patients receiving allogeneic G-CSF-mobilized PBPC from healthy donors and suggests that this might also be true for long-term engraftment.

Adult↗
PubMed1996

Effects of G-CSF administration and peripheral blood progenitor cell collection in 20 healthy donors.

The effects of both daily G-CSF administration and subsequent peripheral blood progenitor cell collection (PBPCC) by apheresis on 20 healthy adult donors were studied. All received daily G-CSF (filgrastim) 10 micrograms/kg for 5-7 days by subcutaneous injection. G-CSF administration was well tolerated, except for moderate bone pain and headache. Peak values of CD34+ cells were observed on days 5 (n = 12) or 6 (n = 8). In all donors a significant increase in CD3+, CD4+, CD8+, CD19+, and NK cells was observed on day 5 in relation to the baseline values. CD4/CD8 lymphocyte ratio was unmodified by G-CSF. None of the donors required a central venous line for PBPCC. Immediately after PBPCC, a platelet count below 100 x 10(9)/1 was observed in nine of 18 cases, although in all donors platelet counts were over 100 x 10(9)/1 7 days later. A lymphocytopenia on day 7 following PBPCC was observed, although there was a tendency to achieve baseline values 30-90 days after the procedure. Mean numbers ( +/- SD) of collected cells x 10(6)/kg after a median of two (1-4) apheresis sessions and a median of 20 1 (10-40) processed were: CD34+ 5.5 ( +/- 2.3), CD3+ 326 ( +/- 105), CD4+ 207 ( +/- 64), CD8+ 164 ( +/- 60), CD19+ 88 ( +/- 32), and NK cells 32 ( +/- 14). We conclude that G-CSF administration to healthy donors is a well-tolerated procedure which is associated with (a) obtaining a high number of hematopoietic progenitor cells, and (b) a significant increase in T, B, and NK cells in donors' blood. In addition, PBPCC by apheresis results in a moderate, rapidly reversible, and clinically irrelevant thrombocytopenia and a moderate lymphocytopenia, which tends to resolve within 3 months following the procedure.

Adolescent↗
PubMed1996

The effect of hormone replacement therapy on bone mass in patients with ovarian failure due to bone marrow transplantation.

BACKGROUND: Long permanent remissions in malignant hematopoietic disorders can often be achieved by autologous bone marrow transplantation (ABMT) or by allogenic bone marrow transplantation (BMT). Previous studies have shown that such therapies may induce osteoporosis due to iatrogenic ovarian failure. The administration of hormone replacement therapy (HRT) in these women could prevent the adverse effects of long-term ovarian failure without remarkable side effects. The aim of this study was to evaluate how the bone mass is affected by HRT in patients undergoing ABMT or BMT adjusting the results for age, weight, and height. SUBJECTS AND METHODS: Thirteen women with previous ABMT/BMT were treated with a standard dose (0.625 mg/day) of conjugated equine estrogen (CEE) or with 50 micrograms/day of 17-beta-estradiol in transdermal therapeutic systems (TTS) plus 5 mg/day of medroxyprogesterone acetate sequentially added to the last 12 days of estrogen therapy. Bone mass was measured prior to and 12 months following HRT. Blood samples were collected before therapy and during the 6th and 12th treatment months. RESULTS: The mean time elapsed between bone transplantation and HRT initiation was 13.0 months (range 3-26 months). Before treatment nine patients were osteopenic and after HRT bone mass increased in all cases. Following ABMT/BMT, hepatic hyperenzymemia was detected in three patients. After 6 and 12 months of treatment no significant changes were observed in hepatic enzymes. CONCLUSION: Although hepatic hyperenzymemia is commonly considered as a contraindication for HRT, our results suggest that HRT is safe for these patients and that such therapy should be initiated after transplantation in women to prevent adverse effects of long-term ovarian failure.

Administration, Cutaneous↗
PubMed1996

A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia. Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY/TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogeneic (BMT)), diagnosis (acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML)), status (early (first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. In ABMT recipients (matched paired 530 x 2) with ALL CR-1, AML CR-1 and AML intermediate disease, transplant-related mortalities (TRM) relapse incidence (RI) and leukaemia-free survival (LFS) did not differ significantly in patients treated with BU/CY or CY/TBI. However, in ABMT recipients with ALL intermediate disease, the probability of relapse was 82 +/- 5% (+/- 95% confidence interval) in the BU/CY group compared to 62 +/- 6% in the CY/TBI group (P = 0.002) and the 2-year leukaemia-free survival 14 +/- 4% and 34 +/- 6%, respectively (P = 0.002). In BMT recipients of bone marrow from HLA-identical siblings (matched paired 391 x 2), the TRM, RI and LFS did not differ significantly between the two treatments in all groups. In particular, the 2-year LFS in patients with AML CR-1 was 64 +/- 3% in those treated with BU/CY (n = 237) compared to 66 +/- 3% in those given CY/TBI (n = 237). In all groups the findings were confirmed in a multivariate analysis of prognostic factors. Veno-occlusive disease (VOD) of the liver (P < 0.05) and haemorrhagic cystitis (P < 0.001) was more common in the BU/CY group compared to the CY/TBI group for ABMT and BMT patients. In conclusion, BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI.

Acute Disease↗
PubMed1996

Undetected viral infection in diffuse alveolar damage associated with bone marrow transplantation.

To investigate the presence of nondiagnosed viral lung infections in patients who developed acute respiratory failure and diffuse pulmonary infiltrates after bone marrow transplantation (BMT), we studied necropsy-obtained lung specimens with features of diffuse alveolar damage (DAD) where no other specific histological diagnosis could be established, by using in situ hybridization and immunohistochemistry. Lung tissue samples obtained at necropsy from 19 patients (12 males and 7 females; 31 +/- 11 yrs mean +/- SD age) who died 56 +/- 36 days after BMT (12 allogeneic and 7 autologous), were studied retrospectively using specific deoxyribonucleic acid (DNA) probes to detect cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV), and adenovirus genomes. Tissue samples were additionally processed with antibodies to CMV and HSV antigens. Cells infected by CMV were detected by in situ hybridization in five cases, and by immunohistochemistry in four cases. Combining the results of both procedures, a previously undiagnosed CMV infection was found in six patients. All of them had received an allogeneic BMT and had developed graft-versus-host disease (GVHD). No evidence of cells infected by HSV, EBV, or adenovirus was found in any case. No viral infection was detected either in recipients of autologous marrow or in recipients of allogeneic BMT without GVHD. These results indicate that pulmonary cytomegalovirus infection not detected by conventional histological examinations may be present in patients with diffuse alveolar damage associated with bone marrow transplantation, especially in recipients of allogeneic marrow who develop graft-versus-host disease. Furthermore, the use of in situ hybridization and/or immunohistochemistry on pulmonary histology might improve the diagnosis of viral lung infections in patients receiving bone marrow transplantation.

Adolescent↗
PubMed1996

Feasibility and results of bone marrow transplantation after remission induction and intensification chemotherapy in de novo acute myeloid leukemia. Catalan Group for Bone Marrow Transplantation.

PURPOSE: To evaluate prospectively the feasibility and results of bone marrow transplantation (BMT) after induction and intensification chemotherapy (CT) in patients with de novo acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 159 patients less than 51 years of age were treated. Induction CT consisted of daunorubicin 60 mg/m2 for 3 days, cytarabine (ARA-C) 100mg/m2 for 7 days, and etoposide 100 mg/m2 for 3 days. The first intensification therapy included mitoxantrone 10 mg/m2 for 3 days and ARA-C 1.2 g/m2 every 12 hours for 4 days. Amsacrine (100 or 150 mg/m2 for 3 days) and ARA-C (1.2 g/m2 every 12 hours for 2 or 4 days) were given as the second intensification therapy. Depending on the availability of a human leukocyte antigen (HLA)-identical sibling, the intention of treatment after CT was allogeneic BMT (allo-BMT) or autologous BMT (ABMT). RESULTS: Complete remission (CR) was obtained in 120 patients (75%) and partial remission (PR) in 11 (7%), while 15 patients (10%) were refractory and 13 (8%) died during induction. There was a trend for better leukemia-free survival (LFS) at 4 years for patients assigned to the ABMT group (50% +/- 6%) compared with the allo-BMT group (31% +/- 7%) (P = .08). This difference in LFS reached statistical significance when considering only transplanted patients (63% +/- 3% at 4 years after ABMT and 38% +/- 11% after allo-BMT, P = .02). The favorable results in patients who received ABMT (no toxic deaths and 37% +/- 7% probability of relapse at 4 years) contrast with the poor outcome of allografted patients (11 patients with transplant-related mortality). CONCLUSION: Our study reflects the difficulties in the completion of a therapeutic strategy that include BMT and suggests that intensification before BMT may be useful in the setting of ABMT, but this approach was associated with a high mortality rate in allo-BMT patients.

Acute Disease↗
PubMed1996

Neurologic complications of autologous and allogeneic bone marrow transplantation in patients with leukemia: a comparative study.

We retrospectively evaluated the neurologic complications in 425 patients who underwent bone marrow transplant (BMT) (310 allogeneic, 115 autologous) for leukemia. Forty-six patients (11%) developed 47 central and three peripheral neurologic complications. The most common complications were cerebral hemorrhage (3.8%), metabolic encephalopathy (3%), and CNS infections (2%). All CNS infections occurred with allogeneic BMT. Eleven of 16 hemorrhages were subdural hematomas (69%), which were more frequent in autologous (8%) than in allogeneic (0.6%) BMT (p < 0.0001), and in patients with acute myelogenous leukemia (AML) (5%) than in the remaining leukemia patients (0.8%) (p = 0.013). Eight of 11 subdural hematomas occurred in AML patients receiving autologous BMT. When we compared patient-, disease-, and transplant-related characteristics of these patients with those without subdural hematoma, only platelet refractoriness correlated with an increased risk of subdural hematoma. The actuarial probability of developing subdural hematoma was 44% in patients with platelet-refractory disease and only 2.5% in the other patients (p < 0.0001). Ten patients with subdural hematoma did not have surgery and eight had significant clinical improvement associated with reduction or resolution of the hematoma, confirmed by CT scan in six patients. The subdural hematoma was the cause of death in only one patient. This study shows that the frequency of the different neurologic complications varies among types of BMT. Patients undergoing autologous BMT for AML with platelet refractoriness have an increased risk of subdural hematoma that may be treated with conservative measures.

Adolescent↗
PubMed1996

Allogenic transplants with peripheral blood progenitor cells: a report of six cases.

Six patients with high-risk leukaemia received a myeloablative regimen followed by allogeneic peripheral blood progenitor cells transplantation (PBPCT) from an HLA-identical sibling donor. Donors received 10-12 mu g/kg/day of G-CSF subcutaneously for 5 days. G-CSF was well tolerated except for moderate bone pain. Peripheral blood leukapheresis product contained 1-4 times more CD34+ cells and approximately a log more of T lymphocytes than marrow grafts from normal donors. In the two first cases the leukapheresis product was partially depleted of T-lymphocytes using counterflow centrifugation. No growth-factors were administered post-transplant. GVHD prophylaxis consisted of cyclosporin A (CyA) in one case, and CyA and methotrexate in five cases. All patients engrafted with a neutrophil count reaching more than 0.5 x 10(9)/L by day 12 to 21 post-transplant and a platelet count above 20 x 10(9)/L by day 6 to 41 post-transplant. Acute GVHD was clinical grade 0 (n = 2), I (n = 1), II (n = I), grade III (n = I) and grade IV (n = 1). One case presents an extensive chronic cutaneous GVHD and is currently being treated with methylprednisolone. In conclusion, allogeneic transplants using PBPC can be performed safely. This may result in a rapid neutrophil and platelet engraftment, without an apparent increased risk of GVHD.

Acute Disease↗
PubMed1996

Physical and psychosocial functioning of 117 survivors of bone marrow transplantation.

All surviving patients receiving a BMT at our center since 1976 were surveyed. Among 163 eligible patients, 145 were contacted and 117 (81%) responded. Their median follow-up was 55 months (range 6-154). The research instruments consisted of a demographic questionnaire, a current medical status form, a quality of life questionnaire (Nottingham Health Profile), and a screening instrument for psychiatric morbidity (the 28-item version of the General Health Questionnaire). Current functioning varied considerably across patients. They reported a high use of medical services (37%) and varied ongoing medical problems within the last 6 months. Most of them (93%) received Karnofsky ratings of 80 or above. Eight percent had current chronic GVHD. Comparing our patients' quality of life with a British reference population, most important differences were found for physical mobility, work, and sex life. Psychiatric morbidity in BMT survivors was higher than in a Spanish general population. Multivariate analyses revealed that a higher systemic symptomatology score, a lower educational level, an older age at BMT, a shorter time post-BMT, a female gender, and impotence were significant predictors of an impaired overall quality of life. Similarly, a higher systemic symptomatology score, a shorter time post-BMT, a higher number of major infections, and a lower educational level were predictive factors of a higher psychosocial distress. No differences in quality of life or psychosocial status between allogeneic and autologous transplants were found. Quality of life and psychosocial distress improved with the passage of time, specially within the first 3 years.

Adolescent↗
PubMed1995

vnd, a gene required for early neurogenesis of Drosophila, encodes a homeodomain protein.

The development of the central nervous system in Drosophila is initiated by the segregation of neuroblasts, the neural progenitors, from the embryonic neuroectoderm. This process is guided by at least two classes of genes: the achaete-scute complex (AS-C) proneural genes and the neurogenic genes. It has been known for some time that loss-of-function mutations in the AS-C result in neural hypoplasia and the first observed defect is failure of segregation of a fraction of neuroblasts. Loss-of-function mutations at the ventral nervous system defective (vnd) locus are known to lead to similar phenotypic defects in early neurogenesis. More recently, the vnd locus has been implicated in the regulation of the proneural AS-C genes and the neurogenic genes of the Enhancer of split complex. In this paper we report the identification of a transcript associated with the vnd locus, the transcript distribution in embryogenesis, which is compatible with the nervous system mutant phenotypes described for this gene, and that the protein product is a member of the NK-2 homeodomain family. We discuss these findings within the framework of early Drosophila neurogenesis and the known phenotypes associated with the vnd locus.

Amino Acid Sequence↗