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J Zuazu

Publications and source records attributed to J Zuazu.

At least 19 recordsLinked to original sources
PubMed2001

The number of donor CD3(+) cells is the most important factor for graft failure after allogeneic transplantation of CD34(+) selected cells from peripheral blood from HLA-identical siblings.

This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells depleted of T cells by CD34(+) positive selection (allo-PBT/CD34(+)) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14. 9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34(+) and CD3(+) cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3(+) cells in the inoculum. Twenty-three of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 x 10(6)/kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 x 10(6)/kg (actuarial probability 18% vs 1%, respectively; P =.0001). The actuarial probability of graft failure progressively increased as the number of CD3(+) cells in the graft decreased, which was determined by grouping the number of CD3(+) cells in quartiles (log-rank P =.03; log-rank for trend P =.003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3(+) cells less than or equal to 0.2 x 10(6)/kg (risk ratio = 17; P <.0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio = 4.8; P =.001). From these results it appears that the number of CD3(+) cells in the inoculum-with a threshold of 0.2 x 10(6)/kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34(+) from HLA-identical siblings. In addition, for patients with CML receiving 0.2 x 10(6)/kg or less CD3(+) cells, total body irradiation might be better than busulphan-based regimens.

Actuarial Analysis↗
PubMed2001

Autologous stem cell transplantation for clinically aggressive non-Hodgkin's lymphoma: the role of preparative regimens.

We investigated the impact of the most commonly used preparative regimens on the outcome of 395 patients with diffuse large cell lymphoma (DLCL), consecutively reported to the registry of the Spanish GEL/TAMO. Among them, 139 (35%) were autografted in 1st CR, 86 (22%) in 2nd/3rd CR, 124 (31%) had chemosensitive disease and 46 (12%) had chemoresistant disease. Conditioning consisted of chemotherapy-only in 348 patients (BEAM, 164; BEAC, 145; and CBV, 39) and radiochemotherapy with CY and TBI in 47. Median times to granulocyte, platelet recovery and to discharge were significantly shorter in the chemotherapy-only group. Early transplant-related mortality was significantly higher when using CY-TBI. After a median follow-up of 28 months, overall survival (OS) at 8 years of patients conditioned with BEAM or BEAC (58% (95% CI 50-66%)) was more favorable than with CBV (40% (95% CI 24-56%)), and significantly better than with CY-TBI (31% (95% CI 18-44%)). Multivariate analysis revealed that patients conditioned with chemotherapy-only regimens had improved OS, disease-free (DFS) and relapse-free survival (RFS) when compared to those conditioned with CY-TBI. Status at transplant was also a powerful prognostic indicator. We conclude that preparative regimens consisting of chemotherapy-only seem more efficacious than CY-TBI as conditioning for DLCL, because of faster engraftment and greater anti-lymphoma effect, as indicated by improved OS, DFS and RFS.

Adolescent↗
PubMed2001

Allogeneic transplantation of CD34+-selected cells from peripheral blood in patients with myeloid malignancies in early phase: a case control comparison with unmodified peripheral blood transplantation.

An allogeneic transplantation of CD34(+)-selected cells from peripheral blood (allo-PBT/CD34(+)) from HLA-identical sibling donors was performed in 50 adult patients with acute myeloid leukemia in first complete remission (AML CR1) (n = 29), myelodysplastic syndrome (MDS) (n = 4), or chronic myeloid leukemia in first chronic phase (CML CP1) (n = 17). Clinical results were compared to a concurrent group of 50 patients transplanted with unmodified peripheral blood progenitor cells (allo-PBT), matched for age, diagnosis, and disease stage. The median follow-up period was 29 months (range 1-69). The actuarial probability of developing acute GVHD clinical grade II to IV was 16% (95%CI: 6-26) for the allo-PBT/CD34(+) group and 41% (95%CI: 29-57) for the allo-PBT group (P = 0.002). The actuarial probability of developing extensive chronic GVHD was 22% (95%CI: 8-36) for the allo-PBT/CD34(+) group and 47% (95%CI: 31-63) for the allo-PBT group (P = 0.02). Recipients of allo-PBT/CD34(+) had less toxicity associated with the transplant and better Karnofsky index at the last follow-up. For AML/MDS patients, the actuarial probability of disease-free survival (DFS) for recipients of allo-PBT/CD34(+) and allo-PBT was 65% (95%CI: 45-85) vs43% (95%CI: 28-58) (P = 0.05), respectively. These data provide a rationale for a randomised trial of allo-PBT/CD34(+) vs allo-PBT in AML/MDS patients in early stage of the disease.

Acute Disease↗
PubMed2001

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

To assess the influence of graft-versus-host disease (GVHD) on the outcome of patients with advanced haematological malignancies (AHM) who received a primary, unmodified allogeneic peripheral blood progenitor cells transplant (allo-PBT) from a human leucocyte antigen (HLA) identical sibling donor, we analysed 136 patients with myeloid neoplasms (n = 70) or lymphoproliferative disorders (n = 66), transplanted at 19 Spanish institutions. Median age was 35 years (range 1-61). The cumulative incidence of relapse for all patients was 34% (95% CI, 26-42%), 41% (95% CI, 33-49) for patients without GVHD and 14% (95% CI, 3-25) (P = 0.001) for patients with acute and chronic GVHD. After a median follow-up of 11 months (range 2-49), 60 (44%) patients remained alive with an actuarial probability of overall survival and disease-free survival (DFS) at 30 months of 31% (95% CI, 21-41%) and 28% (95% CI, 17-39%) respectively. In patients surviving > 100 d, the low incidence of relapse in those with acute and chronic GVHD led to a DFS of 57% (95% CI, 38-76%) compared with a DFS of 34% (95% CI, 17-51%) in the remaining patients (P = 0.03). Our results indicate a reduced incidence of relapse for patients with AHM receiving an unmodified allo-PBT and developing acute and chronic GVHD, which results in an improved DFS.

Acute Disease↗
PubMed2001

Severe infections after allogeneic peripheral blood stem cell transplantation: a matched-pair comparison of unmanipulated and CD34+ cell-selected transplantation.

BACKGROUND AND OBJECTIVES: T-cell depletion of the graft delays immune recovery following allogeneic peripheral blood stem cell transplantation (PBSCT), but it is not clear whether it actually increases the risk of severe infections after the transplant. DESIGN AND METHODS: We have compared the occurrence of severe infections following 162 CD34+ cell-selected allogeneic PBSCT and 162 unmanipulated PBSCT (CD34+ and UM groups, respectively) from HLA-identical siblings. RESULTS: The probability of infection-related mortality (IRM) was 22% in the UM group and 31% in the CD34+ group (log-rank, p=0.2). In multivariate analyses only the use of fluconazole prophylaxis showed a protective effect on IRM in the whole set of patients, while in both transplant groups the most significant factor was the development of moderate-to-severe graft-versus-host disease (GVHD). The probability of developing cytomegalovirus (CMV) infection was 42% in the UM group and 59% in the CD34+ group (p=0.002), with no differences in CMV disease (10% and 9%, respectively). Multivariate analysis of CMV infection identified three variables associated with a higher risk in the whole set of patients: CMV positive serostatus, CD34+ transplant group and recipient age above 40 years. The development of moderate-to-severe GVHD was a significant factor only in the UM group. Disseminated varicella-zoster virus infection was more common in the CD34+ group (19% and 12%, p=0.05), as were early (< 30 days post-transplant) severe bacterial infections (28% vs 14%, p=0.002). Invasive fungal infections and pneumonias of unknown origin did not differ between groups. INTERPRETATION AND CONCLUSIONS: Our results do not show a significant increase in the risk of dying from an opportunistic infection with CD34+-PBSCT, but the risk of CMV infection is increased, with no differences in CMV disease or mortality attributable to CMV. There is an additive effect on IRM of developing moderate-to-severe GVHD (acute or chronic) following CD34+-PBSCT, and in this subset of patients maximum efforts for the prevention and early treatment of opportunistic infections should be pursued.

Adolescent↗
PubMed1999

[Acute leukemia in Jehovah's Witnesses].

Two cases of young patients, Jehova Witnesses (JW), diagnosed as having acute lymphoblastic leukaemia are presented. In one case a complete remission (CR) was obtained, lasting until now, 20 months after diagnosis; the other one died 11 months after diagnosis without achieving a CR. Three important questions can be raised in JW: 1) the absolute respect to patients' wishes; 2) to treat or not to treat; and 3) the pertinent therapy. The answer is yes to 1) and 2), and a slight myelotoxic therapy for the last one.

Adult↗
PubMed1998

Allogeneic transplantation of selected CD34+ cells from peripheral blood: experience of 62 cases using immunoadsorption or immunomagnetic technique. Spanish Group of Allo-PBT.

The objective of this study was to analyze CD34+ cell recovery and T cell depletion (TCD) achieved in CD34+ cell grafts using either immunoadsorption or immunomagnetic methods applied to leukapheresis products from healthy donors. We also wanted to determine the kinetics of engraftment and incidence and severity of graft-versus-host disease (GVHD) after allogeneic transplantation of selected CD34+ cells. HLA-identical sibling donors received G-CSF. After leukapheresis, peripheral blood progenitor cells were selected using immunoadsorption (Ceprate SC) (n = 38) or immunomagnetic (Isolex 300) (n = 24) methods. Sixty-two patients, with a median age of 42 years (range 17-60) diagnosed with hematological malignancies were conditioned with either cyclophosphamide and total body irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11) and CsA and methotrexate (n = 3). The median yield and purity of CD34+ cells after the procedure was 65 and 66% with immunoadsorption, and 48 and 86% with immunomagnetic method, respectively. The median number (range) of CD34+ cells infused into the patients was 3.5 x 10(6)/kg (1-9.6). The median number (range) of CD3+ cells administered was 0.4 x 10(6)/kg (0.01-2) using immunoadsorption and 0.14 x 10(6)/kg (0.03-2.5) using immunomagnetic methods. Neutrophil recovery >500 and >1000/microl was achieved at a median (range) of 13 days (8-22) and 14 days (9-31), respectively. Platelets recovered to >20000 and >50000/microl at a median (range) of 13 days (0-128) and 18 days (0-180), respectively. Two patients developed graft failure. Acute GVHD in patients at risk was clinical grade 0 (n = 43), I (n = 8), II (n = 4) and III (n = 1). No patient developed acute GVHD grade IV. Chronic GVHD was limited in two cases and extensive in four cases. The actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of extensive chronic GVHD was 12% (95% CI, 11-13%). The cumulative incidence of transplant-related mortality was 12.6%, and this figure was 9% at 6 months. In conclusion, with the immunomagnetic procedure, a lower recovery and higher purity of CD34+ cells, and stronger TCD is obtained as compared to immunoadsorption (P = 0.008, P < 0.0001 and P = 0.0002, respectively). Our results also indicate that allogeneic transplantation of selected CD34+ cells is associated with a very rapid engraftment and with a low incidence of severe GVHD.

Acute Disease↗
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↗
PubMed1998

Late intensification chemotherapy has not improved the results of intensive chemotherapy in adult acute lymphoblastic leukemia. Results of a prospective multicenter randomized trial (PETHEMA ALL-89). Spanish Society of Hematology.

BACKGROUND AND OBJECTIVE: Intensive induction and post-remission therapies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensification therapy in the overall results of treatment has not been consistently evaluated. The objective of this study was to analyze the results of a multicenter prospective protocol, PETHEMA ALL-89, in which, after intensive induction and consolidation therapy, randomization to receive delayed intensification treatment was performed. DESIGN AND METHODS: One hundred and eight adults (age > or = 15 years) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the end of the first year were randomized to receive one six-week cycle of late intensification therapy. Uni- and multivariate analyses of early response to treatment, complete remission (CR), leukemia-free survival (LFS) and overall survival (OS) were performed. RESULTS: The median (range) age of the series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34 months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-year probability 47% (34-59%). There were no differences in either LFS and OS between patients who did or did not receive delayed intensification therapy. Prognostic factors for CR attainment were advanced age and slow response to therapy. These two features were, in addition to high leukocyte counts, the parameters with negative influence in both LFS and OS. INTERPRETATION AND CONCLUSIONS: The results of PETHEMA ALL-89 are similar to those referred in other chemotherapy-based protocols in adult ALL. Delayed intensification has not improved the length of remission and survival. Efforts to improve the prognosis of adult ALL patients must be mainly focused in early intensification treatment.

Adolescent↗
PubMed1998

Allogeneic transplantation of purified CD34+ cells from peripheral blood: Spanish experience of 62 cases. Spanish Group of allo-PBT.

This report summarizes the Spanish experience of 62 cases of allogeneic transplantation of purified CD34+ cells from peripheral blood. HLA-identical sibling donors received G-CSF. After leukapheresis, peripheral blood progenitor cells were purified using one of two methods: Ceprate (n = 38), or Isolex 300 (n = 24). Sixty-two patients median age 42 years (range 17-60) diagnosed with hematological malignancies were conditioned with either cyclophosphamide and total body irradiation (n = 43) or busulphan and cyclophosphamide (n = 19). GVHD prophylaxis consisted of cyclosporin A (CsA) and prednisone (n = 48), CsA alone (n = 11), and CsA and methotrexate (n = 3). The median yield and purity of CD34+ cells after the procedure was 65% and 66% with Ceprate, and 48% and 86% with Isolex, respectively. The median number of CD34+ cells infused into the patients was 3.5 x 10(6)/kg (range 1-9.6). The median number of CD3+ cells administered was 0.4 x 10(6)/kg (range 0.01-2) using Ceprate and 0.14 x 10(6)/kg (range 0.03-2.5) using Isolex. Neutrophil recovery >500 and >1000/microl was achieved at a median of 13 days (range 8-22) and 14 days (range 9-31), respectively. Platelets recovered to >20,000 and >50,000/microl at a median of 13 days (range 0-128) and 18 days (range 0-180), respectively. The actuarial probability of acute GVHD II-IV was 10% (95% CI, 1-19%), and of extensive chronic GVHD 12% (95% CI, 11-13%).

Adolescent↗
PubMed1998

[Enterobacter amnigenus. An unusual human pathogen].

BACKGROUND: Enterobacter amnigenus is a bacteria with doubtful pathogenicity. The observation of a patient with a well-documented E. amnigenus infection has prompted us to review the pathology caused by this microorganism. METHODS: Retrospective evaluation of the clinical charts of patients with any isolate positive for E. amnigenus over a period of 46 months. Based on the clinical data, presence or absence of other causal microorganisms and/or alternative diagnosis, E. amnigenus was classified as definitive, probable, or improbable cause of infection. RESULTS: We analyzed 15 E. amnigenus isolates, representing 0.97 of 10,000, the total bacterial isolates in our laboratory for this period, and 0.52% of those corresponding to Enterobacter sp. We were able to clinically evaluate E. amnigenus in 7 patients, in whom infection by this microorganism was classified as definitive in 4, probable in 1, and improbable in 2. Antibiotic susceptibility studies showed a resistance level of 83% to ampicillin, 75% to cefazoline and cefoxitine, and 33% to amoxicillin-clavulanic acid. All isolates were susceptible to third-generation cephalosporins, aztreonam, ciprofloxacin, cotrimoxazole and aminoglycosides. CONCLUSIONS: E. amnigenus cause well-documented bacterial infection in man. Thus, isolation of this microorganism should not be considered as a contaminant or simple colonizer. The clinical behavior and antimicrobial susceptibility of E. amnigenus is similar to that of E. cloacae, a taxonomically-related species.

Aged↗
PubMed1991

Pregnancy outcome in hematologic malignancies.

By means of a mail questionnaire, information on a series of 56 pregnancies i in 48 women diagnosed with leukemia or lymphoma was collected from ten hospitals. Seven patients conceived while receiving treatment for their neoplasms; in 22 patients, the hematologic disease was diagnosed during pregnancy, and the remaining 27 patients became pregnant after completion of the antineoplastic treatment. When a comparison was made of the evolution of these pregnancies to that of pregnancies in a healthy population, no increase in the incidence of complications was observed: 64% of the pregnancies went to term, 9% resulted in spontaneous abortion, and 5% resulted in premature births. The observed incidence of one major malformation in 56 pregnancies did not differ from the frequency of malformations in the offspring of healthy individuals. There were no fetal losses in six pregnancies in which conception occurred during the first year after chemotherapy. In spite of the inherent limitations derived from the design of this type of study and the type of subject analyzed, the data here support the hypothesis that the cytostatic treatment of hematologic malignancies, if deemed necessary, should not be postponed because of pregnancy. Moreover, the authors agree with advice recommending that no antifolic or alkylating agents be used for prolonged periods and that radiotherapy be avoided, especially to those fields involving the pelvic area.

Abortion, Induced↗
PubMed1989

[Autoimmune hemolytic anemia and myelodysplastic syndromes].

The association between autoimmune haemolytic anaemia (AHA) and myelodysplastic syndromes (MDS) was found in seven out of 156 patients with SMD who received several transfusions as supportive therapy. Three patients were diagnosed of refractory anaemia (RA), three more of refractory anaemia with excess of blasts (RAEB) and one of refractory anaemia with ring sideroblasts (RARS). All patients showed a positive direct antiglobulin test (DAT) and the presence of anti-red blood cell IgG type antibodies, both in serum and eluate. Clinically, three patients showed signs of low grade haemolysis. It is suggested that in the reported patients, who seem to be immunologically predisposed, red blood cell transfusions could trigger the autoantibodies and the AHA development.

Anemia, Hemolytic, Autoimmune↗
PubMed1989

[Vindesine, CCNU, high-dosage ara-C, and prednisolone (VINAP regimen) in the treatment of relapsing or refractory non-Hodgkin's lymphomas].

Results of second line chemotherapy schedules to treat refractory lymphoma have usually been poor. In this study we have treated 21 patients with advanced non-Hodgkin's lymphoma, usually heavily pretreated, with VINAP regimen. This original four drug chemotherapy combination included: Vindesine, 2 mg/m2 iv on days 1 and 2; CCNU, 40 mg/m2 oral on days 3 and 4; Cytosine arabinoside, 2.4 g/m2 iv on day 3 to 6 and methyl-Prednisolone, 80 mg/m2 on days 1 to 6. Sixteen patients (76%) showed response, including 5 (23%) who achieved a complete remission (CR). Eight patients achieved a partial remission (PR), and two patients obtained an objective response. Although the responses to VINAP regimen were dramatic and rapid in onset, usually they were of short duration except in cases of lymphosarcoma cell leukaemia. The median duration of response for patients with CR was 42 weeks and for PR 11 weeks. Toxicity was acceptable, including predictable myelosuppression, frequent mucositis and occasional polyneuritis. Neither central nervous problems nor conjunctivitis or dermatitis had been seen.

Adolescent↗