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Biomedical subjects

M A Diaz

Publications and source records attributed to M A Diaz.

At least 19 recordsLinked to original sources
PubMed2002

Matched-pair analysis comparing allogeneic PBPCT and BMT from HLA-identical relatives in childhood acute lymphoblastic leukemia.

This multicenter study was designed to evaluate whether allo-PBPCT provides some advantages, if any, over BMT in terms of engraftment kinetics, acute and chronic GVHD incidence, TRM, relapse incidence and survival in acute lymphoblastic leukemia patients (ALL). From January 1995 to December 1999, 67 ALL patients (34 in the PBPCT group and 33 in the BMT group) were included in this study. Median age for both groups was 8 years (range, 1-18). There were 24 patients in first or second CR in the PBPCT group and 28 such patients in the BMT group. Preparatory regimens were TBI-based in 26/34 in the PBPC group and 25/33 in the BMT group. GVHD prophylaxis was CsA alone in 38 patients (18 PBPCT vs 20 BMT) and CsA plus short Mtx in 29 (16 PBPCT vs 13 BMT). Engraftment was achieved in all cases. Median days to neutrophil recovery was 10 (range, 7-18) after PBPCT vs 14 (range, 9-21) after BMT (P < 0.0001). Platelet engraftment (>50 x 10(9)/l) was also faster for PBPCT patients (median 13 days, range, 9-40 vs 23 days, range, 15-165) (P < 0.0001). Acute GVHD grade II-IV incidence was similar in both groups (46.4 +/- 8.8% vs 42.7 +/- 8.6%) (P = 0.45). Probability of chronic GVHD was 50.6 +/- 12.2% after PBPCT vs 27.8 +/- 9.2% after BMT (P = 0.1). Probability of relapse was similar (28.7 +/- 9.2% for PBPCT vs 27.1 +/- 8.2% for BMT) (P = 0.89). There were eight patients who died from transplant-related complications after PBPCT vs 5 after BMT (P, NS). With a median follow-up of 25 months the event-free survival probability was 53 +/- 8.9% for PBPCT vs 54.9 +/- 9.7% for BMT (P = 0.54). Using PBPC for allogeneic transplantation in childhood ALL results in faster hematopoietic recovery compared to BM, with a similar incidence of aGVHD, TRM, relapse and disease-free survival. However, the issue of cGVHD remains unresolved.

Adolescent↗
PubMed2001

Allogeneic peripheral blood stem cell transplantation (PBSCT) from HLA-identical sibling donors in children with hematological diseases: a single center pilot study.

Between February 1995 and July 1999 25 pediatric patients (8 months to 14 years old) underwent peripheral blood stem cell transplantation (PBSCT) from an HLA-identical sibling donor. Diagnoses included ALL (17), non-ALL (6), and non-malignant disease (2). GVHD prophylaxis consisted of cyclosporine plus methotrexate (15), only cyclosporine (8), cyclosporine plus prednisone (1), or nothing (1). All donors (6 months to 41 years old) received G-CSF at 10 microg/kg/day subcutaneously for 4-5 days and on day 5 underwent large volume leukapheresis. Median number of CD34(+) and CD3(+) cells collected and infused was 6.9 x 10(6) (range 2.5-32.8) and 4.5 x 10(8) (0.5-22.1) per kg of recipient body weight respectively. Median time to achieve ANC >0.5 x 10(9)/l and platelets >20 x 10(9)/l was 10 and 12 days, respectively. Acute GVHD grade > or =II developed in 10 of 24 evaluable patients (42%). Probability of acute GVHD was 62%. Median time to discharge was 25 days (range 14-52). Among 20 evaluable patients, five (25%) developed chronic GVHD at day 100. Probability of chronic GVHD was 29% after 1 year post PBSC. At a median follow-up of 558 (9-2071) days, overall survival for the whole group is 68%. Probabilities of event-free survival, overall survival and relapse for patients with malignant hematological diseases are 53%, 59% and 24% at 5 years, respectively. This study has confirmed the feasibility and safety of mobilization and collection of PBSC products and the applicability of this procedure to the pediatric population, both donors and recipients. Studies including larger numbers of pediatric patients undergoing allogeneic PBSCT are warranted to determine the long-term outcomes of such procedures.

Adolescent↗
PubMed2001

Molecular, antigenic, and functional analyses of Omp2b porin size variants of Brucella spp.

Omp2a and Omp2b are highly homologous porins present in the outer membrane of the bacteria from the genus Brucella, a facultative intracellular pathogen. The genes coding for these proteins are closely linked in the Brucella genome and oriented in opposite directions. In this work, we present the cloning, purification, and characterization of four Omp2b size variants found in various Brucella species, and we compare their antigenic and functional properties to the Omp2a and Omp2b porins of Brucella melitensis reference strain 16M. The variation of the Omp2a and Omp2b porin sequences among the various strains of the genus Brucella seems to result mostly from multiple gene conversions between the two highly homologous genes. As shown in this study, this phenomenon has led to the creation of natural Omp2a and Omp2b chimeric proteins in Omp2b porin size variants. The comparison by liposome swelling assay of the porins sugar permeability suggested a possible functional differences between Omp2a and Omp2b, with Omp2a showing a more efficient pore in sugar diffusion. The sequence variability in the Omp2b size variants was located in the predicted external loops of the porin. Several epitopes recognized by anti-Omp2b monoclonal antibodies were mapped by comparison of the Omp2b size variants antigenicity, and two of them were located in the most exposed surface loops. However, since variations are mostly driven by simple exchanges of conserved motifs between the two genes (except for an Omp2b version from an atypical strain of Brucella suis biovar 3), the porin variability does not result in major antigenic variability of the Brucella surface that could help the bacteria during the reinfection of a host. Porin variation in Brucella seems to result mainly in porin conductivity modifications.

Amino Acid Sequence↗
PubMed2001

Comparative cost analysis of autologous peripheral blood progenitor cell and bone marrow transplantation in pediatric patients with malignancies.

BACKGROUND AND OBJECTIVES: This study was conducted in order to compare and analyze clinical and economic outcomes of autologous transplantation using bone marrow or peripheral blood as the source of hematopoietic progenitor cells in pediatric patients with malignancies. DESIGN AND METHODS: We collected clinical information and resource utilization from 131 consecutive autologous transplantations (102 peripheral blood progenitor cell (PBPC) and 29 bone marrow (BM) transplants) at a single institution between January 1989 and December 1998 in children with a variety of malignancies. Multivariable linear regression was used to evaluate the associations between pre-transplantation variables, post-infusion events and overall costs. A cost-effectiveness analysis of transplantation for acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) patients was also performed. RESULTS: Hematopoietic recovery was faster in the PBPCT group (days to neutrophil and platelet engraftment: 9 and 13, respectively, versus 14 and 21 for BMT, p<0.0001). There were less transfusion, antibiotic and parenteral nutrition requirements and hospital stay was shorter (median 17 days; range 8-38) in the PBPCT group than in the BMT one (median 28 days; range 11-65) (p<0.0001) resulting in a median lower overall cost for PBPCT (US$ 7895) compared to BMT (US$ 11820)(p<0.0001). Major determinants of overall costs for both groups were total body irradiation (TBI)-based conditioning regimen, days of hospitalization and number of transfused platelets. In PBPCT patients, a graft containing > or = 5 x 10(6)/kg CD34+ cells decreased the total cost of transplantation by 27%. Cost-effectiveness was higher for PBPCT than BMT for pediatric AML patients (p<0.0001) whereas in ALL patients the cost-effectiveness of the two transplant strategies was not significantly different. INTERPRETATIONS AND CONCLUSIONS: We conclude that, compared to BMT, autologous PBPCT in children is associated not only with clinical benefits but also economic advantages.

Adolescent↗
PubMed2000

Autologous stem cell transplantation for advanced Hodgkin's disease in children. Spanish group for BMT in children (GETMON), Spain.

This study evaluates the outcome of myeloablative chemo-radiotherapy and autologous stem cell transplantation (ASCT) in children with Hodgkin's disease (HD). Twenty children aged 5 to 18 years (median 10.8 years) at diagnosis, with relapsed, refractory or very poor prognosis HD, underwent ASCT in eight hospitals of our country. Status at transplant was: second complete remission (CR2): n = 12; further CR (CR >2): n = 3, partial remission (PR): n = 2, relapse: n = 2 and first CR (CR1): n = 1. Eighteen patients received chemotherapy-based conditioning regimens: cyclophosphamide, carmustine and etoposide (CBV): 11 (55%), carmustine, etoposide, cytarabine and melphalan (BEAM): 5, other: 2; and two patients were conditioned with TBI/Cy. Peripheral blood (PB) was the source of progenitor cells in 12 patients, BM in seven, and BM plus PB, in one. All patients engrafted. One patient died of sepsis and multiorgan failure at day 28 after transplantation. All four patients with measurable disease (PR or relapse) at transplantation attained complete remission. Five patients relapsed 5-34 months after transplant (median: 11 months). Eighteen children remain alive with a median survival time of 40 months. The projected 5-year overall survival and event-free survival (EFS) rates were 0.95 and 0.62. High-dose therapy with stem cell rescue can lead to durable remissions in children with advanced HD. Bone Marrow Transplantation (2000) 25, 31-34.

Adolescent↗
PubMed2000

Long-term hematopoietic engraftment after autologous peripheral blood progenitor cell transplantation in pediatric patients: effect of the CD34+ cell dose.

BACKGROUND AND OBJECTIVES: We analyzed the relationship between long-term hematopoietic recovery and the number of CD34+ cells infused in order to determine the optimal dose of CD34+ cells for rapid and stable engraftment. PATIENTS AND METHODS: Between November 1993 and December 1998, 96 consecutive autologous transplantations were performed in 92 pediatric patients with different malignancies. Peripheral blood progenitor cells (PBPC) were mobilized by G-CSF alone (12 microg/kg/day s.c., Neupogen((R)); Amgen, Thousand Oaks, Calif., USA) and collected using a Cobe Spectra blood cell separator (Cobe, Denver, Colo., USA) through a central venous catheter with double lumen. The CD34+ cell contents of apheresis products were assessed by means of flow-cytometric analysis using an Epics Elite flow cytometer (Coulter, USA). RESULTS: The median number of CD34+ cells infused was 3.2 x 10(6)/kg (range 0.17-44.4). The median times for short-term engraftment (neutrophil count >0.5 x 10(9)/l and platelet count >20 x 10(9)/l) was 9 (range: 7-16) and 13 days (range: 7-91), respectively. The median times for long-term engraftment (platelet count >50 x 10(9)/l and >100 x 10(9)/l) was 21 (range: 10-249) and 45 days (range: 12-288). When the infused CD34+ cell dose was >/=5 x 10(6)/kg (median 7.99, range 5.01-44.4), there was a statistically significant increase in the rate of short- and long-term hematopoietic recovery compared to patients transplanted with a lower number of CD34+ cells (p < 0.0001). The earlier recovery in the high CD34+ cell group resulted in less transfusional support, fewer days on intravenous antibiotics and shorter hospitalization. CONCLUSIONS: This study confirms that G-CSF-mobilized PBPC provide rapid short- and long-term hematopoietic engraftment in pediatric patients undergoing autologous transplantation if a CD34+ cell dose >/=5.0 x 10(6)/kg is infused. As this PBPC dose seems to have clinical and potentially economic implications, it should be considered the optimal dose for apheresis.

Adolescent↗
PubMed1999

High-dose busulfan/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors.

We conducted a prospective pilot study to assess the feasibility and safety of high-dose busulfan/melphalan as conditioning therapy prior to autologous PBPC transplantation in pediatric patients with high-risk solid tumors. From January 1995 to January 1999, 30 patients aged 2-21 years (median 8) were entered into the study. There were 14 females and 16 males. Diagnoses included neuroblastoma in 10 patients; Ewing's sarcoma and peripheral neuroectodermal tumor (PNET) in 15 patients and rhabdomyosarcoma in five patients. Treatment consisted of busulfan 16 mg/kg, orally over 4 days (from days -5 to -2) in 6 hourly divided doses, and melphalan at a dose of 140 mg/m2 given by intravenous infusion over 5 min on day -1. G-CSF mobilized PBPC were used as autologous stem-cell rescue. One patient developed a single generalized convulsion during busulfan therapy. The most relevant non-hematologic toxicity was gastrointestinal, manifesting as grade 2-3 mucositis and diarrhea in 12 patients. Two patients died of procedure-related complications, one from veno-occlusive disease of liver and multiorgan failure and the other from adult respiratory distress syndrome. Probability of treatment-related mortality was 6.6 +/- 4.5%. With a median follow-up of 18 months (range, 1-48), 19 patients are alive and disease-free, the actuarial EFS at 4 years being 55 +/- 12% for the whole group. We conclude that high-dose busulfan/melphalan for autologous transplantation in children with solid tumors is feasible even in small patients. It is well-tolerated, with an acceptable transplant-related mortality and has proven antitumor activity.

Adolescent↗
PubMed1998

Peripheral blood progenitor cell collection by large-volume leukapheresis in low-weight children.

Large-volume leukapheresis (LVL), defined as the processing of at least three blood volumes in a single session for peripheral blood progenitor cell (PBPC) collection, was performed in 32 small children weighing < or = 25 kg, aged 10 months to 8 years, with a variety of malignancies. Harvesting of PBPC was started after 4 days of cytokine (G-CSF, 12 micrograms/kg s.c.) alone. Procedures were performed using a continuous flow blood cell separator (COBE Spectra). The automated program of lymphocytapheresis was modified to achieve a collection rate of 0.9 ml/min. The extracorporeal line was primed with a unit of a packed red blood cells before the procedure. Acid citrate dextrose (ACD) was used as anticoagulant with an ACD inlet ratio of 1:14 and an ACD infusion rate of 1.1 ml/min/L of total blood volume. The inlet flow ranged between 6 and 35 ml/min (median 20 ml/min). A total of 37 apheresis procedures were performed (median 1, range 1-3). In 84% of patients, a single apheresis yields the minimum number of PBPC cells required for transplantation. No consistent side effects were observed, and LVL was well tolerated by children. A median of 7.7 x 10(8) kg MNC, 5.4 x 10(6)/kg CD34+, and 6.2 x 10(4)/kg CFU-GM per apheresis were harvested. Patients with neuroblastoma had a significantly lower yield than other patients. To date, 27 patients have been transplanted after myeloablative treatment, and rapid and sustained engraftment was achieved in all cases. The number of CD34+ cells infused was highly correlated with engraftment kinetics. LVL can be safely and easily performed in small children, allowing adequate PBPC collection for transplantation with rapid hematologic recovery.

Blood Specimen Collection↗
PubMed1998

Peripheral blood progenitor cells for autologous transplant in children.

Autologous peripheral blood progenitor cell transplantation has become an accepted procedure to support high dose chemotherapy in adults and children with cancer. The use of hematopoietic growth factors alone for mobilization of PBSC avoids the potential side effects of myelotoxic regimens and is as effective in reconstituting hematopoiesis as other mobilization methods. Many problems associated with apheresis procedures arise when PBPCs are harvested in small children. Large-volume-leukapheresis using a continuous flow blood cell separator allows us the collection of peripheral blood stem cells in children, even in the small ones. The speed of hematological recovery highly correlates with the number of CD34+ infused cells. We consider that a CD34+ cell dose of 5.0 x 10(6)/kg may be sufficient to ensure a rapid neutrophil and platelet recovery in pediatric patients mobilized by G-CSF.

Antigens, CD34↗
PubMed1997

Allogeneic peripheral blood progenitor cell (PBPC) transplantation in children with haematological malignancies.

We report on five children with haematological malignancies who underwent allogeneic peripheral blood progenitor cell (PBPC) transplantation. PBPC were harvested from HLA-identical sibling donors after G-CSF (10 micrograms/kg/d s.c.) mobilization. Aphereses were carried out on day 5 after G-CSF using a Cobe Spectra blood cell separator. All PBPC allografts were cryopreserved before transplantation. The median of CD34+ cells and CD3+ cells infused were 14.1 x 10(6)/kg recipient body weight (range 4.92-22.3) and 2.40 x 10(8)/kg recipient body weight (range 0.54 4.82), respectively. Engraftment occurred in all cases. The median time to a neutrophil count > 0.5 x 10(9)/l and a platelet count > 20 x 10(9)/l were 15 and 14 d, respectively. The incidence of severe acute graft-versus-host disease was 20%. These data suggest that allogeneic PBPC transplantation might be an alternative to bone marrow transplantation in children.

Child↗
PubMed1996

Acylfulvenes, a new class of potent antitumor agents.

Acylfulvene, derived from the sesquiterpene illudin S by treatment with acid (reverse Prins reaction), is far less reactive to thiols than illudin S. However, it is reduced readily to an aromatic product, in the same way as illudin S. This may explain its greatly improved therapeutic index compared to that of the parent compound.

Animals↗
PubMed1996

Collection and transplantation of peripheral blood progenitor cells mobilized by G-CSF alone in children with malignancies.

Results of collection and transplantation of peripheral blood progenitor cells (PBPC) mobilized by G-CSF in 31 children with different malignancies were analysed. A total of 43 aphereses were performed, following administration of granulocyte colony-stimulating factor (G-CSF), using a continuous flow blood cell separator (Cobe Spectra) through a central venous catheter. For patients weighing 0.5 x 10(9)/l and a platelet count of 20 x 10(9)/l without platelet support were 9.5 and 18, respectively. The number of CD34+ cells infused correlated highly with engraftment kinetics. The extra-medullary toxicity was low and manageable.

Adolescent↗
PubMed1996

A unique dysembryonic neoplasm of the adrenal gland composed of nephrogenic rests in a child.

A primary neoplasm of the right adrenal gland in a 4-year-old boy was discovered after the patient developed bowel obstruction following an appendectomy. Until the histologic examination, the tumor was thought to be a neuroblastoma. However, the intra-adrenal tumor was composed of blastematous nodules, primitive tubules, and glomeruloid structures whose overall composition resembled a Wilms' tumor. Other than a single focus of mucinous glands, the tumor lacked the range of somatic tissue types of a teratoma. Approximately 50 cases of putative extrarenal Wilms' tumor have been reported. The retroperitoneum is one of the more common primary sites, yet our case is the first documented example of a neoplasm with features of a Wilms' tumor arising in the adrenal. Based on the embryologic and anatomic relationship between the adrenal gland and kidney, it is somewhat surprising that other instances of similar appearing tumors have not been described before the present case. Our patient was managed on a Wilms' tumor protocol and remains tumor free 15 months after surgery.

Adrenal Gland Neoplasms↗
PubMed1996

Non-tunneled catheters in children undergoing bone marrow transplantation.

We analyzed the use of non-tunneled (polyurethane double lumen) central venous catheters (CVCs) in 62 children undergoing bone marrow transplantation. The catheters were inserted in the Critical Care Unit without surgery or general anesthesia. The complications were pneumothorax in two patients and hemopneumothorax in two other patients (6.06%), entry site infection in six patients (9.6%), catheter-related infection in eight patients (12.9%) and catheter-related sepsis in nine patients (14.5%). The catheters were removed upon completion of therapy in 46 patients (74.1%), death in seven patients (11.3%) and in nine cases (14.5%) for infection. Despite the complications specific to non-tunneled catheter insertion, we believe this is indicated for patients during conditioning, transplantation and immediate post-transplantation periods.

Adolescent↗