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J M Moraleda

Publications and source records attributed to J M Moraleda.

At least 37 records · Page 2Linked to original sources
PubMed2000

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). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P = 0.003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26-68] compared with 43% (CI 31-54) for MEL140 + TBI and 37% (CI: 18-56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 + TBI groups respectively. These differences were non-significant (P = 0.2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 + TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P = 0.01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.

Busulfan↗
PubMed2000

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). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17-53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57-86, median not reached) compared with any other response group (univariate comparison P < 0.00000 to P = 0. 004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0.6; median survival 56, 44 and 42 months respectively, P = 0.5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0.00000; OS P < 0.00000; both Cox models P < 0.00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF.

Electrophoresis↗
PubMed1999

Autoaggression syndrome resembling acute graft-versus-host disease grade IV after autologous peripheral blood stem cell transplantation for breast cancer.

Acute graft-versus-host disease (aGVHD) after autologous progenitor cell transplantation has been associated with blood transfusion or cyclosporine. Mild aGVHD grades I-II, identified as autoaggression or engraftment syndrome, has recently been described in autologous progenitor transplantation. Here, we report the first case of pathologically documented grade IV aGVHD after autologous peripheral blood progenitor cell transplantation in a patient with breast cancer. The allogeneic origin was excluded by molecular techniques, and no cyclosporine or cytokines were administered.

Adult↗
PubMed1998

Polymorphisms of platelet membrane glycoprotein Ib associated with arterial thrombotic disease.

Platelet membrane glycoprotein Ibalpha (GPIbalpha) is a major receptor for von Willebrand factor and thrombin, which plays a key role in the initial development of thrombi. Two polymorphisms (HPA-2 and VNTR) that affect phenotype have been described in GPIbalpha. The relevance of these polymorphisms to thrombotic disease was investigated by genotypic identification in three case-control studies: 104 case patients with acute cerebrovascular disease (CVD), 101 case patients with acute coronary heart disease (CHD), 95 patients with deep venous thrombosis (DVT), and one control age-, sex-, and race-matched for each case patient. Results show that the C/B genotype of the VNTR and the HPA-2b polymorphisms of GPIbalpha are strongly associated with increased risk of coronary heart disease and cerebral vascular disease but not with deep vein thrombosis. These two polymorphisms of GPIbalpha may represent newly identified risk factors for arterial thrombotic disease, but not for venous thrombosis.

Adult↗
PubMed1998

Bone marrow steady-state CD34+/CD71- cell content is a predictive value of rG-CSF-mobilized CD34+ cells.

Thirty-four patients diagnosed with breast cancer were included in a prospective study evaluating the bone marrow (BM) CD34+/CD71- cell content, as a predictive parameter of the CD34+ cell mobilization after rG-CSF administration. Analysis of the concentration of medullary CD34+/CD71- cells before priming schedules was significantly related with the collection of CD34+ cells in apheresis day 1 (P = 0.03, r = 0.36), apheresis day 1 + day 2 (P = 0.01, r = 0.42) or the total CD34+ cells collected (P = 0.005, r = 0.47). A BM CD34+/CD71- cell concentration greater than or less than a cut-off value of 30/microl was significantly associated with the yield of CD34+ cells collected by cytapheresis procedures (mean values 3.12 x 10(6)/kg, and 2.19 x 10(6)/kg, respectively, P = 0.013). These results suggest that in breast cancer patients undergoing priming with rG-CSF, steady-state BM CD34+/CD71- measurement is a relevant predictive parameter of CD34+ mobilization.

Adult↗
PubMed1998

Chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation from matched related donors. A case-control study. Spanish Group of Allo-PBT.

We retrospectively compared the incidence and clinical characteristics of cGVHD in 37 allo-PBT recipients transplanted between July 1994 and October 1996 and 37 historical control allo-BMT recipients in a case-control study. All patients received a first unmanipulated transplant, graft from an HLA-identical sibling donor, with CsA-MTX GVHD prophylaxis and survived more than 100 days after transplant. PBT and BMT groups were well matched for age, grade of acute GVHD, male patients grafted from female donors, and phase of disease. The median CD34+ and CD3+ cell numbers infused in the PBT group were 5.2 x 10(6)/kg and 307 x 10(6)/kg, respectively. The median time to an ANC greater than 0.5 x 10(9)/l was 16 days (range 11-22) after PBT and 22 days (range 14-36) after BMT (P < 0.001). The median time to a platelet count greater than 20 x 10(9)/l was 15 days (range 6-43) after PBT and 28 days (range 12-68) after BMT (P < 0.001). Median follow-up was 12.3 months (range 5.4-30.3) and 58.7 months (range 4-122.3), for patients receiving PBT and BMT, respectively. Seventeen out of 37 (46%) PBT recipients, vs nine out of 37 (24%) BM recipients developed cGVHD. Actuarial probability of cGVHD at 1 year was 59% (95% CI, 39-79) in the PBT group vs 27% (95% CI, 12-42) in the BM group (P = 0.01). Cumulative incidence estimate of cGVHD was 51% and 25%, for patients receiving PBT and BMT respectively (P = 0.03). Clinical characteristics of cGVHD and response to therapy were similar in both groups, except for a higher incidence of de novo cGVHD in the PBT group. Our results suggest that as compared with BMT, PBT may result in an increased incidence of cGVHD.

Adolescent↗
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

BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors.

In the present paper, we evaluate tolerability, outcome and prognostic factors in patients with poor prognosis non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) when uniformly treated with BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem cell transplant (ASCT). On hundred and forty-eight patients with NHL (n = 112) or HD (n = 36) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14). Twenty-eight patients had low-grade lymphoma (LGL), 68 intermediate- and 16 high-grade lymphoma (IGL). Within the NHL group, 21 patients were in 2nd or subsequent complete remission (CR) at transplant, 34 had sensitive disease and 11 resistant disease; 46 patients were transplanted in 1st CR due to the presence of > or = 2 adverse prognostic features at diagnosis or to a slow CR. Of the HD patients at transplant 17 had active disease, 16 were in > or = 2 CR and three in 1st CR. The overall percentage of toxic deaths was 5.4%, while in the group of patients transplanted with PBSC it was only 1.3%. NHL patients: 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease. Only two of the 11 patients transplanted with resistant disease achieved CR. Incidence of overall survival (OS) and disease-free survival (DFS) at 3 years was 65 and 75%, respectively. As far as histology was concerned, OS was significantly better for patients with LGL in comparison with IGL (88 vs 56%) (P = 0.002). DFS was significantly higher for patients transplanted in first CR or first partial remission (PR) than it was for those transplanted in a later CR or PR (86 vs 53%) (P = 0.02). Multivariate analysis for OS showed that histology, bulky disease, poor performance status at transplant and achievement of CR were independent prognostic factors. In addition, a high number of infused MNC was associated with poor DFS. HD patients: 30 (83%) were in CR after transplantation, with 25 maintaining CR at the end of the study. Only one of the four patients transplanted with resistant disease reached CR. Incidence of OS and DFS at 3 years was 78 and 81%. DFS was similar for patients transplanted with early or late relapse (95 and 93%). With multivariate analysis, the only independent variable for OS was CR after transplant. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other strategies should be investigated for patients with refractory lymphoma.

Adolescent↗
PubMed1997

Prospective randomized study comparing the efficacy of bioequivalent doses of glycosylated and nonglycosylated rG-CSF for mobilizing peripheral blood progenitor cells.

Thirty patients diagnosed with breast cancer were included in a prospective randomized study comparing the in vivo priming effect of bioequivalent doses of glycosylated (lenograstim) and nonglycosylated (filgrastim) rG-CSF administration. Analysis of the efficacy of equivalent biological doses of both rG-CSFs showed no significant differences either in the mobilization of the subpopulations of PBPC considered (CD34+, CD34+/38-, CD34+/DR-), the content of such CD34+ cell subsets in the leukapheresis product, or the cost of the mobilization and collection procedures between both recombinant molecules. These results suggest that priming with bioequivalent doses of the two commercially available forms of glycosylated or nonglycosylated rG-CSF has a similar in vivo effect on PBPC mobilization.

Adult↗
PubMed1997

Loss of high-affinity thrombin receptors during platelet concentrate storage impairs the reactivity of platelets to thrombin.

BACKGROUND: The storage of platelet concentrates (PCs) induces a reduction in the platelet surface expression of glycoprotein (GP) Ib alpha. The location of the platelets' high-affinity binding site for thrombin has been postulated as being located on GPIb alpha. This study attempts to determine whether loss or alteration of GPIb alpha during storage of PCs is related to impairment in the reactivity of platelets to thrombin. STUDY DESIGN AND METHODS: In this study, platelet surface expression of GPIb alpha was monitored by means of flow cytometry, throughout standard storage of PCs for up to 10 days. Two thrombin-induced platelet responses, the binding of radiolabeled fibrinogen and the platelet surface expression of P-selectin, were evaluated. Thrombin-binding assays were also performed to assess the number of thrombin receptors in platelets. RESULTS: The surface expression of the GPIb/IX complex declines during storage of PCs. The thrombin-induced maximal binding of fibrinogen in platelets stored for 3, 7, and 10 days was 77 +/- 7 percent, 60 +/- 20 percent, and 34 +/- 25 percent, respectively, of that found in fresh platelets. Moreover, the concentration of thrombin needed for 50 percent of platelets to express the CD62 antigen P-selectin at the surface increased from 0.05 U per mL in fresh platelets to 0.11, 0.56, and 1.2 U per mL in platelets stored for 3, 7, and 10 days, respectively. Thrombin-binding experiments demonstrated a significant reduction in the number of high-affinity binding sites throughout storage of PCs (55 +/- 21 sites/platelet in 10-day-stored platelets vs. 73 +/- 25 in fresh platelets). A significant correlation was also observed between the number of high-affinity thrombin-binding sites and surface expression of GPIb alpha. Selective blockage of the thrombin-binding site on GPIb alpha with monoclonal antibody LJ-Ib10 also inhibited the response of fresh platelets to thrombin, up to a level equivalent to that found in 3-day-stored platelets. CONCLUSION: The loss of the GPIb alpha-located high-affinity thrombin-binding site may impair the ability of platelets to become activated by thrombin as storage time increases.

Antibodies, Monoclonal↗
PubMed1996

[Economic costs of autotransplantation of hematopoietic progenitors].

BACKGROUND: A comparative analysis of the economic costs of the different methods of autologous transplantation was carried out. METHODS: A series of 22 patients was retrospectively studied: 8 treated with autologous bone marrow transplantation (ABMT), 9 treated with peripheral blood stem cell (PBSC) transplantation and 5 in whom mixed transplantation of bone marrow and peripheral blood hematopoietic progenitors was performed. The expenses derived from pretransplant studies and from the collection of hematopoietic progenitors and from the autologous transplantation procedure itself were evaluated. RESULTS: The pretrasplant study and the collection of hemopoietic progenitors were significantly more expensive in the PBSC than in the ABMT (p = 0.04 and p = 0.007, respectively). Nonetheless, the costs of the transplant procedure were lower in the PBSC than in the ABMT group although the differences were not statistically significant. The estimated costs of these procedures in the Hematology Unit of the General Hospital of the University of Murcia, Spain, is of 3 million pesetas for the ABMT and 2.5 million for the PBSC. The greatest cost observed in the ABMT was due to these patients requiring longer hospitalization, greater transfusion support and longer antibiotic treatment. CONCLUSIONS: Although the collection of hematopoietic progenitors and pretransplant evaluation are less expensive in autologous bone marrow transplantation, the early morbidity is higher than that of peripheral blood stem cell transplantation or mixed autotrasplanted of bone marrow and circulating progenitors thus resulting in higher costs.

Adolescent↗
PubMed1996

Immune recovery after autologous or rhG-CSF primed PBSC transplantation.

We performed a prospective study in 17 consecutive patients following Autologous bone marrow (BM) or rhG-CSF primed peripheral blood item cell (PBSC) transplantation, with the objective of comparing immune recovery between both procedures and to evaluate results in rhG-CSF mobilized peripheral blood stem cell transplantation (PBSCT). Kinetics of immune reconstitution showed differences, with a faster recovery of CD3+ and CD8+ T cells, and a more rapid and sustained recovery of CD8+/-/CD56+ natural killer (NK) cells in the PBCSCT group. Autologous bone marrow transplantation (ABMT) was associated with a improved reconstitution of the CD19+/CD5+/-subpopulation. Moreover, rhG-CSF mobilized PBSCT generated a greater recovery of CD8+/-/CD56+ cells than previous data concerning transplantation with peripheral blood (PB) progenitors collected after myelosuppressive chemotherapy or myelosuppressive therapy plus rhG-CSF. Our results show differences in the rate and pattern of B and T lymphocytes reconstitution after ABMT and PBSCT. Additionally, we state an enhancement of CD56+ cells in patients undergoing PBSCT mobilized solely using rhG-CSF.

Adolescent↗