PubMed Health⌕ Search

Biomedical subjects

V Rocha

Publications and source records attributed to V Rocha.

At least 19 recordsLinked to original sources
PubMed2007

Haematopoietic stem cell transplantation trends in children over the last three decades: a survey by the paediatric diseases working party of the European Group for Blood and Marrow Transplantation.

This paper describes the trends in haematopoietic stem cell transplantation (HSCT) activity for children in Europe over the last three decades. We analysed 31,713 consecutive paediatric HSCTs reported by the European Group for Blood and Marrow Transplantation (EBMT) centres between 1970 and 2002. Data were taken from the EBMT registry and were compared according to period and centre category (paediatric or combined). Since 1996, there has been a significant increase in the number of HSCTs performed exclusively by paediatric centres, as well as in the number of alternative donor HSCTs, and in the use of peripheral blood stem cells (P<0.0001). The number of allogeneic HSCTs (allo-HSCTs) for acute lymphoblastic leukaemia, acute myeloblastic leukaemia and chronic myeloid leukaemia remained stable, whereas it increased for myelodysplastic syndromes and lymphomas, and decreased significantly for non-malignant diseases (P<0.0001). Multivariate analysis showed that younger age, human leukocyte antigen genoidentical donors, HSCT performed after 1996 and transplant centres performing more than 10 allo-HSCT/year were all associated with decreased transplant-related mortality (TRM) (P<0.0001). The number of autologus HSCTs (auto-HSCTs) for acute leukaemia decreased significantly, whereas it increased for solid tumours (P<0.0001). Multivariate analysis showed that both auto-HSCT performed before 1996 and paediatric solid tumours (P<0.0001) had higher TRM. Indications for paediatric HSCT have changed considerably during the last seven years. These changes provide tools for decision making in health-care planning and counselling.

Blood Transfusion↗
PubMed2006

HLA-identical sibling allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning compared to autologous peripheral blood stem cell transplantation for elderly patients with de novo acute myeloid leukemia.

We conducted a retrospective registry-based analysis to compare the outcome of 361 allogeneic human leukocyte antigen (HLA)-identical peripheral blood stem cell transplants (PBSCT) with reduced intensity conditioning (RIC) to that of 1369 autologous (auto) PBSCT in patients aged 50 years or older with de novo acute myeloid leukemia (AML), performed from 1997 until 2003 and reported to the European Group for Blood and Marrow Transplantation. Median age was 58 and 57 years in the RIC and auto groups, respectively. RIC patients had more advanced disease at the time of transplant. At a median follow-up of 24 months for RIC and 16 months for auto, multivariate analysis showed a lower risk for relapse (RR 0.77, P=0.013) without increased non-relapse mortality (NRM) in RIC patients (RR 1.26, P=0.28). Moreover, leukemia-free survival (RR 1.22, P=0.02) and overall survival (OS) (RR 1.32, P=0.005) were superior in the RIC group. In patients in 1st (CR), fewer relapses were counterbalanced by significantly increased NRM. Therefore, there was no survival advantage in this subgroup. In patients in 2nd or subsequent CR, LFS and OS were superior in the RIC group. RIC transplants show encouraging results in this older patient population with de novo AML.

Aged↗
PubMed2006

Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders.

Combinations of HLA and killer immunoglobulin-like receptors (KIR) may affect outcome in T-cell depleted haematopoietic stem cell transplantation (HSCT). The KIR gene family includes inhibitory (KIR2DL and 3DL) and activating receptors (KIR2DS). Ligands are HLA-C (KIR2D) and HLA-Bw4 (KIR3DL1) for inhibitory KIR and are still unknown for activating KIR. The impact of activating KIR genotypes from donor and recipient is poorly documented in HSCT outcome. Here, HLA and KIR genotypes were determined in 131 pairs from non-T-cell depleted HLA-identical sibling HSCT. No effect of 'missing KIR ligand' was detected on acute graft-versus-host disease (GVHD), relapse, survival or infections even in myeloid malignancies. However, additional activating KIR genes in the donor compared to the recipient's genotype or an identity between donor and recipient activating KIR genotypes was associated with a lower transplant-related mortality (TRM) (P=0.005) and in a multivariate analysis with a better survival (P=0.02, HR=0.28; P=0.013, HR=0.29) and a lower incidence of cytomegalovirus (CMV) reactivation (P=0.009, HR=0.36). These data highlight the impact of donor-activating KIR genes on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT.

Adolescent↗
PubMed2006

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe.

The Accreditation Subcommittee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published in 1996. Haemopoietic stem cell transplantation today includes grafting with allogeneic and autologous stem cells derived from bone marrow, peripheral blood and cord blood. With reduced intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged such as autoimmune disorders and AL amyloidosis for autologous, and solid tumours for allogeneic transplants. The introduction of alternative therapies has challenged well-established indications such as imatinib for chronic myeloid leukaemia. An updated report with revised tables and operating definitions is presented here.

Europe↗
PubMed2005

Use of intrathecal prophylaxis in allogeneic haematopoietic stem cell transplantation for malignant blood diseases: a survey of the European Group for Blood and Marrow Transplantation (EBMT).

SUMMARY: A survey was carried out among EBMT centres to describe the current practice concerning intrathecal (i.t.) prophylaxis in allogeneic stem cell transplantation for malignant diseases in patients with no central nervous system (CNS) manifestations of the disease at any time. A total of 90 centres reported their practice: 42 centres (47%) never used pre-transplant i.t. prophylaxis as part of the conditioning, whereas 48 centres (53%) gave i.t. prophylaxis to selected groups. The main indications were acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and lymphoma (53, 33, and 23% of all centres, respectively). Prophylaxis was usually given to all patients with ALL, but often restricted to high-risk patients in AML and lymphoma. Of the 90 centres, 29 (32%) gave prophylactic i.t. treatment after the transplantation, mainly for the same indications as pre-transplant. This survey illustrates the heterogeneity in the current practice of i.t. prophylaxis in allogeneic transplantation for malignant blood disorders in Europe. The documentation in the literature to support the use of i.t. prophylaxis as part of transplantation for malignant diseases in patients without preceding CNS involvement is sparse. Based on the rarity of isolated CNS relapse after allogeneic stem cell transplantation, EBMT does not recommend routine i.t. prophylaxis to patients without prior CNS involvement.

Antineoplastic Agents↗
PubMed2005

Granulocyte colony-stimulating factor for poor graft function after allogeneic stem cell transplantation: 3 days of G-CSF identifies long-term responders.

Poor graft function (PGF) is a frequent cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To study the value of granulocyte colony-stimulating factor (G-CSF) in PGF, we retrospectively analyzed 81 episodes of PGF in 66 patients transplanted from 01/94 to 01/99 from an HLA-identical sibling (n = 45) or an unrelated (n = 21) donor. Median age was 29 years, 55 patients had malignancies. A total of 11 patients received a CD34+ selected graft. Viral infections (25%), myelotoxic drug (33%), fungal/bacterial infections (14%), and GVHD (31%) were present before PGF diagnosis. Median time from allo-HSCT to PGF was 75 (25-474) days. All patients were treated with G-CSF. In 77/81 episodes, there was a response that was sustained in 57. A total of 27 patients presented an increase of white cell count (WBC) >0.1 x 10(9)/l after 3 days of G-CSF. The 5-year survival was 37% and was significantly better in patients with increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (65 vs 18%, P < 0.0001). In multivariate analysis, increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (P = 0.002) was associated with better survival, while BuCy-based conditioning (P = 0.02) and GVHD (P = 0.005) were associated with higher risk of death. In conclusion, hematological response after 3 days with G-CSF predicted a better survival for patients with PGF after allo-SCT.

Adolescent↗
PubMed2005

Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time.

We analysed a large homogeneous group of 14,403 patients transplanted for early leukaemia from an HLA-identical sibling and reported to the EBMT in four time cohorts: 1980-1989 (24%), 1990-1994 (26%), 1995-1998 (30%) and 1999-2001 (20%). We focused on death from infection. End points were survival, death from relapse and transplant-related mortality (TRM), which was subdivided into death from graft-versus-host disease (GvHD) (1315 patients; 25% of deaths), infection (597 patients; 11% of deaths) or 'other' causes (1875 patients; 34% of deaths). Survival increased from 52% at 5 years in the first to 62% in the third cohort (P<0.05) and TRM decreased from 36 to 26% (P<0.05) due to a reduction in death from infection (P<0.001). GvHD, 'other' causes and relapse did not improve. The relative proportions of bacteria (217 patients; 36%), viruses (183 patients; 31%), fungi (166 patients; 28%) or parasites (32 patients; 5%) as cause of infectious death (cumulative incidence of death at 5 years 1.8, 1.6, 1.4 and > or = 0.3%, respectively) and median time to death from infections (3 months (range 0-158 months)) did not change. Death from infections has been reduced significantly, but it still represents an ongoing risk after HSCT and draws attention to the time beyond the initial period of neutropenia.

Adolescent↗
PubMed2005

High-resolution HLA typing by sequencing for HLA-A, -B, -C, -DR, -DQ in 122 unrelated cord blood/patient pair transplants hardly improves long-term clinical outcome.

To determine the impact of high-resolution (HR) HLA typing with outcomes after UCBT, DNAs of 122 pairs were analysed for HLA class I and class II mismatches (MM) based on HR typing. For HLA-A, -B on low-resolution typing and -DRB1 on HR typing, the following MM situation resulted: no MM (13%), one MM (40%), two MM (36%), three MM (8%), four MM (3%). For A, B, C, DR and DQ based on HR typing the following MM occurred: No MM (4%), one MM (10%), two MM (15%), three MM (22%), four MM (25%), five MM (12%), six MM (6%), seven MM (3%), eight MM (2%). There was no significant association between number of MM (HR) for both HLA-A, -B and -DRB1 and HLA-A, -B, -C, -DRB1 and DQB1 and aGvHD grade II-IV. There was a trend that MM in class I HR were associated with neutrophil recovery; HLA-A locus typing analysed in HvG direction was associated with reduced cumulative incidence of engraftment (P=0.04), the same for C-KIR in HvG direction (P=0.01). No significant correlation was found between numbers of HLA-MM on the HR level with 2-year survival. The analysis shows that the degree of mismatching in UCBT is even higher than expected.

ABO Blood-Group System↗
PubMed2005

A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors.

We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.

Follow-Up Studies↗
PubMed2005

Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT).

Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II-IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10(-4), respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.

Aged↗
PubMed2005

History of the clinical use of umbilical cord blood hematopoietic cells.

The first cord blood (CB) transplant was performed in 1988 in a patient with Fanconi anemia. The donor was his HLA-identical sister who was known by pre-natal diagnosis to be HLA identical and not affected by the Fanconi mutation. The CB was collected and cryopreserved at birth. The transplant was successful without GvHD and the patient is currently alive and free of disease more than 15 years after transplant, with full hematologic and immunologic donor reconstitution. At the time of the first transplant, little was known about the biologic properties of CB cells and it was thanks to the pioneering work of H. E. Broxmeyer and E. A. Boyse, who studied the progenitor cell content of CB, and of A. D. Auerbach, who realized the pre-natal diagnosis of Fanconi anemia, that this transplant was possible. Since this first transplant, many questions have been answered but others are still open for further research. For example: would a single CB unit contain enough stem cells to permanently engraft children and adults? Would maternal cell contamination in fetal blood engraft and give severe GvHD? What are the immunologic properties of CB cells? How does it interfere with GvHD, GvL and immune reconstitution? Is the immune immaturity of CB lymphocytes able to overcome the HLA barrier and authorize HLA-mismatched transplants? Is it possible to establish CB banks for unrelated and related transplants? What would be the criteria for collection, quality control and cryopreservation?

Child↗
PubMed2002

Transplantation of peripheral blood stem cells as compared with bone marrow from HLA-identical siblings in adult patients with acute myeloid leukemia and acute lymphoblastic leukemia.

PURPOSE: Several studies show that allogeneic peripheral blood stem cells (PBSCs) engraft more rapidly than bone marrow (BM). However, the data are inconsistent with regard to acute and chronic graft-versus-host disease (GVHD), relapse, transplant-related mortality (TRM), and leukemia-free survival (LFS). PATIENTS AND METHODS: Between January 1994 and December 2000, 3,465 adult patients (older than 15 years of age) were reported to the European Group for Blood and Marrow Transplantation Registry from 224 centers. Among acute myeloid leukemia (AML) patients, 1,537 patients received BM and 757 patients received PBSC. In acute lymphoblastic leukemia (ALL) patients, the corresponding figures were 826 versus 345 patients who were analyzed for engraftment, GVHD, TRM, relapse, LFS, and survival. RESULTS: In multivariate analysis, the recovery of neutrophils and platelets was faster with PBSC than with BM (P <.0001). Chronic GVHD was associated with PBSC in patients with AML (relative risk [RR], 2.11; 95% confidence interval, 1.66 to 2.7; P <.0001) and ALL (RR, 1.56; 95% confidence interval, 1.09 to 2.27; P =.02). PBSC versus BM in patients with AML or ALL was not significantly associated with acute GVHD, TRM, relapse, survival, or LFS. In multivariate analysis of patients with AML, factors significantly associated with improved LFS included first remission at transplant (P <.0001), promyelocytic leukemia (M3) versus other French-American-British types (P <.0001), and donor age below median 37 years (P =.02). In patients with ALL, first remission (P <.0001) and methotrexate included in the immunosuppressive regimen (P =.001) were associated with improved LFS. CONCLUSION: Allogeneic PBSC results in faster neutrophil and platelet engraftment and a higher incidence of chronic GVHD than BM. However, acute GVHD, TRM, relapse, survival, and LFS were similar in patients receiving PBSCs versus BM.

Acute Disease↗
PubMed2001

Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.

In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]: 0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P <.07). In conclusion, the use of UCBT, as a source of hematopoietic stem cells, is a reasonable option for children with AL lacking an acceptably matched unrelated marrow donor.

Analysis of Variance↗
PubMed2001

Influence of bone marrow graft lymphocyte subsets on outcome after HLA-identical sibling transplants.

OBJECTIVE: The aim of this study was to analyze bone marrow lymphocyte subsets and CD34 cell dose and their influence on the outcomes of bone marrow transplantation. MATERIALS AND METHODS: Forty-eight patients (median age 30 years, range 5-54) receiving HLA-identical sibling bone marrow transplantation for hematologic malignancies were analyzed. RESULTS: Median number (range) of nucleated cells and CD34+ cells infused were 2.4 (0.4-6.0) x 10(8)/kg and 3.5 (0.5-13.0) x 10(6)/kg, respectively. Probability of neutrophil recovery was 97%. In a multivariate analysis, time to neutrophil recovery was shortened when a higher number of CD3/CD8 cells was infused (> or =1.0 x 10(7)/kg) (hazard ratio [HR] = 2.13, p = 0.018); when the patient was female or had negative cytomegalovirus serology (HR = 2.03, p = 0.03; HR = 0.41, p = 0.009; respectively). The incidence of grade II to IV acute graft-vs-host disease (GVHD) was 47%. Infusion of >1 x 10(7) CD4 infused/kg increased the risk of acute GVHD (HR = 2.86, p = 0.03). Nineteen of 40 patients at risk experienced chronic GVHD, the risk of which was increased by diagnosis of chronic leukemia (p = 0.03), <2.0 x 10(8) nucleated cells infused/kg (p = 0.05), and a low number of all lymphocyte subsets, except CD19. Estimated 3-year survival rate was 54%. Risk of death was increased in patients receiving <3.5 x 10(6)CD34 infused/kg (HR = 0.37, p = 0.02). Only six patients relapsed. CONCLUSIONS: A high cell dose of CD3/CD8 is associated with faster neutrophil recovery, whereas a high cell dose of CD4+ cells increases the incidence of acute GVHD. A high number of nucleated cells and CD34+ cells infused was associated with decreased risk of chronic GVHD and improved survival, respectively.

Acute Disease↗
PubMed2001

Results of unrelated umbilical cord blood hematopoietic stem cell transplant.

The number of umbilical cord blood transplants (UCBT) is increasing worldwide, and the purpose of Eurocord is to evaluate the results and compare the outcome of UCBT with allogeneic bone marrow transplants (BMT). Data have been reported to Eurocord by many transplant centers. Close links have been established with cord blood banks through Netcord. BMT data have been provided by transplant centers and also by the European Blood and Marrow Transplant (EBMT) and International Bone Marrow Transplant Registries (IBMTR). Eurocord has analyzed the outcome of unrelated UCBT from 121 transplant centers and 29 countries. The results have shown that survival with unrelated mismatched UCBT was comparable to that with unrelated BMT. Engraftment with cord blood was delayed, resulting in an increased incidence of early transplant complications. The incidence of acute and chronic graft-versus-host-disease (GVHD) was reduced with cord blood grafts even in HLA mismatched transplants and in adults. In patients with leukemia, the rate of relapse was similar to that after BMT. The overall event-free survival with UCBT was not statistically different when compared to BMT. In conclusion, this large registry study confirms the potential benefit of using umbilical cord blood hematopoietic stem cells for allogeneic transplants.

Adolescent↗