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G F Sanz

Publications and source records attributed to G F Sanz.

At least 19 recordsLinked to original sources
PubMed2005

Transplantation of CD34+ selected peripheral blood to HLA-identical sibling patients with aplastic anaemia: results from a single institution.

We evaluated the use of CD34+ selected allogeneic peripheral blood as a source of hematopoietic progenitors for allogeneic transplantation in 11 patients with aplastic anemia (AA). The median age was 17 years (range, 6--9), and the median time between diagnosis and transplant 1 month (range, 1--4). Conditioning consisted of cyclophosphamide (50 mg/kg per day) on days--7 to--4 and antithymocyte globulin (30 mg/kg per day) on days--4 to--2 in nine patients. Total lymphoid irradiation was added to the preparative regimen for two. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and prednisone. Median doses of CD34+ and CD3+ cells infused were 3.91 x 10(6) and 0.3 x 10(6)/kg, respectively. The median time taken to achieve a neutrophil count >0.5 x 10(9)/l was 12 days and to recover a platelet count >20 x 10(9)/l, 13 days. Two patients developed acute GVHD grade I--II and one developed limited chronic GVHD. There were two treatment-related deaths. At a median follow-up of 44 months (range, 4--3), nine patients were alive with sustained and complete engraftment. This is a promising procedure in patients with AA, resulting in a rapid hematopoietic recovery, a low transplant-related mortality, and a low incidence of GVHD.

Adolescent↗
PubMed2003

Factors influencing the collection of peripheral blood stem cells in patients with acute myeloblastic leukemia and non-myeloid malignancies.

Factors influencing the collection of autologous peripheral blood stem cells (PBSCs) were studied in 182 mobilization procedures performed on 145 consecutive patients with acute myeloblastic leukemia (AML; n=67) and with various non-myeloid malignancies (NMM; n=78). PBSC were collected following mobilization with chemotherapy, treatment with granulocyte colony-stimulating factor (G-CSF) or chemotherapy plus G-CSF. Fewer colony-forming unit granulocyte-macrophages (CFU-GMs) were collected from patients with AML than from patients with NMM (P<0.0001), although there were no differences in the numbers of CD34+ cells collected between both groups. Multiple regression analysis showed that chemotherapy alone was predictive of a low CD34+ yield in patients with NMM (regression coefficient (RC)=-2.1; P=0.003). In addition, the interactions "diagnosis mutliple myeloma (MM)xmobilization with chemotherapy" (RC=2.9; P=0.004) and "diagnosis MMxmobilization with chemotherapy plus G-CSF" (RC=2.1; P=0.04) also remained in the model, both showing a favorable influence. In AML, mobilization with chemotherapy plus G-CSF was associated with higher CD34+ yields (P=0.003). In this subgroup of patients, multiple regression analysis identified the number of cycles of previous chemotherapy (< or =2 cycles; RC=1.3; P=0.03) and peripheral blood counts (WBC > or =1.5 x 10(9)/l and monocytes >20%; RC=0.8; P=0.02) as the factors most predictive of CD34+ cell yield. These findings emphasize the need to optimize harvesting technique to enhance safety and minimize morbidity and costs of this valuable procedure.

Acute Disease↗
PubMed2002

Early infections in adult patients undergoing unrelated donor cord blood transplantation.

Early transplant-related mortality after cord blood transplantation from unrelated donors (UD-CBT) is close to 50%, mainly due to infectious complications. We have studied the incidence and characteristics of early infections (before day 100) in a series of 27 adult patients (median age 30 years, range 16-46) undergoing UD-CBT at a single institution. All 27 patients experienced at least one infectious episode and 18 (66%) suffered a severe infection. Bacteremia occurred in 55% of patients (13 with Gram-positive and 11 with Gram-negative microorganisms). Eleven of 19 CMV-seropositive patients (58%) developed CMV antigenemia and one patient had CMV disease. Fungal infections were documented in three patients (11%), comprising invasive fungal infections in two cases and a localized esophagitis in one. Ten patients (37%) died before day 100 after transplantation. Infection was considered the primary cause of death in four patients (sepsis by Acinetobacter spp. bacteremia in three cases) and contributed to death in another four. The most striking findings in this series were the high incidence of, and mortality due to multiresistant Acinetobacter spp. and the low incidence of and lack of mortality due to CMV disease. This report confirms that infection is a major complication in adults undergoing UD-CBT.

Acinetobacter Infections↗
PubMed2002

Unrelated donor umbilical cord blood transplantation in adults.

Umbilical cord blood (UCB) has emerged as an appealing alternative source of hematopoietic stem cells for unrelated donor transplantation. Shorter time to transplant and an improved chance of finding a suitable graft are evident advantages over bone marrow transplantation from unrelated donors. The majority of UCB transplants from unrelated donors have been performed in children, but the number in adults has been growing steadily in recent years. We review herein the reported experience with that source of hematopoietic stem cells in adults with hematological malignancies. The available data support the use of UCB transplantation from unrelated donors for young adults with hematological malignancies and no appropriate bone marrow donor, especially for those requiring urgent transplantation.

Adult↗
PubMed2002

Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution.

OBJECTIVE: To analyze the incidence and characteristics of documented infections in patients with hematologic malignancies undergoing unrelated donor bone marrow transplantation (UD-BMT). METHODS: We studied the occurrence of infections in 22 patients with hematologic malignancies or severe aplastic anemia who underwent UD-BMT from April 1990 to December 2000. The median age was 26 years (range 13-46). Acyclovir-ganciclovir, co-trimoxazole, fluconazole-nystatin and ciprofloxacin were administered for anti-infectious prophylaxis. RESULTS: We registered 61 infectious episodes. During the early post-transplant period, there were eight clinically documented infections (CDIs), four cases of fever of unknown origin (FUO), seven cases of bacteremia, two cases of cytomegalovirus (CMV) antigenemia, and one case of CMV disease. In the intermediate period (days 30-100 after BMT), there were nine cases of CMV antigenemia, three bacterial infections, two fungal infections, one case of disseminated toxoplasmosis, and one case of FUO. In the late period (day 100 and later), we documented 13 viral infections, eight bacterial infections, one CDI, and one case of invasive aspergillosis. Infections contributed to death in 10 of 17 patients. Citrobacter bacteremia and sepsis of unknown origin were the main causes of infectious mortality in the early period. Infection was the main cause of death in six of seven patients in the late period. CONCLUSION: A high incidence of life-threatening infections and infection-related mortality was observed. A high rate of CMV infection in the early period, and death caused by multiresistant Gram-negative microorganisms in the late period, were the main findings in this series.

Adolescent↗
PubMed2001

Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years), and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range, 13-52 days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor.

Adult↗
PubMed2001

Transplant-related mortality in patients older than 60 years undergoing autologous hematopoietic stem cell transplantation.

Although high-dose therapy with autologous hematopoietic stem cell transplantation (ASCT) is a widely used method of dose intensification in patients with hematological malignancies, patients aged over 60 are generally excluded. We evaluated high-dose therapy and ASCT in 29 cases involving 27 such patients (median age 63 years; range 61-68) with different malignancies. Patients were eligible if they had a good performance status, normal cardiac, respiratory, and hepatic function and a serum creatinine concentration of less than 2 mg/dl (<5 mg/dl in myeloma patients). Engraftment was assessable in 27 procedures. The median time to attain 0.5 and 1 x 10(9) PMN/l was 13 days (range 9-30) and 14 days (range 10-66), respectively. The median time taken to reach a platelet count greater than 50 x 10(9)/l was 14 days (range 8-223). Five patients (17%) died in the first 100 days after transplant, in two cases due to disease progression. The remaining three patients died as a consequence of transplant-related complications, with an overall transplant-related mortality of 10%. Five patients relapsed and died between 5 and 36 months after transplant. The remaining 17 patients are still alive without disease progression, with an actuarial overall survival of 47% at 42 months (95% CI 33-61). We consider that high-dose therapy with ASCT should be considered in those elderly patients with good performance status and without general organ impairment.

Aged↗
PubMed2001

Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution.

The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults is not well established. We report the results of UD-CBT in nine adult patients with chronic myeloid leukemia (CML). The median age was 27 years (range, 19-41 years), and the median weight was 62 kg (range, 45-78 kg). At transplant, six patients were in chronic phase (five in first, and one in second), two in blast crisis, and one in accelerated phase. Eight had received intensive chemotherapy, and three had undergone autologous peripheral blood hematopoietic stem cell transplantation. Four had received interferon with no cytogenetic response, and only three underwent UD-CBT within 1 year of diagnosis. After serological typing for class I antigens, and high-resolution DNA typing for DRB1, the degree of HLA match between patients and cord blood (CB) units was 4/6 in six cases and 5/6 in three cases. The median number of nucleated cells infused was 1.7 x 10(7)/kg (range, 1.2 to 4.9 x 10(7)/kg), and was above 2 x 10(7)/kg in only two cases. All patients received thiotepa, busulfan, cyclophosphamide and anti-thymocyte globulin as conditioning; cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis; and G-CSF from day +7 until engraftment. All seven evaluable cases engrafted. The median time to reach an absolute neutrophil count > or =0.5 x 10(9)/l and > or =1 x 10(9)/l was 22 days (range, 19-52 days) and 28 days (range, 23-64 days), respectively. In the four patients evaluable for platelet recovery time to levels of > or =20 x 10(9) platelets/l, > or =50 x 10(9) platelets/l, and > or =100 x 10(9) platelets/l, these ranged from 50 to 128 days, 60 to 139 days, and 105 to 167 days, respectively. Three patients developed acute GVHD above grade II, and three of the five patients at risk developed extensive chronic GVHD. Four patients, all transplanted in chronic phase, remain alive in molecular remission more than 18, 19, 24 and 42 months after transplantation. These preliminary results suggest that UD-CBT may be considered a reasonable alternative in adults with CML who lack an appropriate bone marrow donor.

Acute Disease↗
PubMed2001

Marked reduction in the incidence of hepatic veno-occlusive disease after allogeneic hematopoietic stem cell transplantation with CD34(+) positive selection.

Veno-occlusive disease of the liver (VOD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). To determine the incidence of, and the risk factors for the development of VOD, we performed a retrospective analysis of a series of 178 patients, who underwent allogeneic HSCT at our institution between 1990 and 1999. Busulfan and cyclophosphamide constituted the conditioning regimen most frequently administered. Bone marrow was the source of stem cells in 129 patients (73%), and peripheral blood (PBSC) in 49 patients (27%). Thirty-one patients of the PBSC group received CD34(+) positively selected grafts. Most patients were given cyclosporin A and methotrexate (MTX) as graft-versus-host disease (GVHD) prophylaxis. Overall, 30 patients (17%) developed VOD. In univariate analyses, the incidence of VOD was significantly higher in recipients of unmanipulated grafts (20% vs 0%; P = 0.01), in patients with active malignant disease at transplantation (24% vs 9%; P = 0.03), in recipients of marrow from unrelated donors (33% vs 15%; P = 0.03), in patients grafted with bone marrow (21% vs 6%; P = 0.03), and in those receiving MTX as GVHD prophylaxis (21% vs 6%; P = 0.05). Under multivariate analysis, only CD34(+) positive selection (P = 0.0004) and the status of the disease at transplant (P = 0.03) were statistically significant variables for the development of VOD. We conclude that CD34(+) positively selected PBSC transplantation could result in a marked reduction in the incidence of VOD after allogeneic HSCT.

Adolescent↗
PubMed2001

Absence of platelet response after eradication of Helicobacter pylori infection in patients with chronic idiopathic thrombocytopenic purpura.

Eradication of Helicobacter pylori infection has been associated with the correction of thrombocytopenia in patients with idiopathic thrombocytopenic purpura (ITP). We have analysed the response to eradication of H. pylori in a series of 56 adult patients with chronic ITP. Forty patients had H. pylori infection (71%) that was eradicated in 23 of 32 evaluable patients (72%). Platelet counts did not significantly vary according to H. pylori treatment outcome. Three of 56 patients (5%) achieved a partial response attributable to H. pylori eradication. Therefore, detection of H. pylori infection should not be routinely included in the initial work-up of ITP.

Adolescent↗
PubMed2000

Report of an international working group to standardize response criteria for myelodysplastic syndromes.

Standardized criteria for assessing response are essential to ensure comparability among clinical trials for patients with myelodysplastic syndromes (MDS). An international working group of experienced clinicians involved in the management of patients with MDS reviewed currently used response definitions and developed a uniform set of guidelines for future clinical trials in MDS. The MDS differ from many other hematologic malignancies in their chronicity and the morbidity and mortality caused by chronic cytopenias, often without disease progression to acute myeloid leukemia. Whereas response rates may be an important endpoint for phase 2 studies of new agents and may assist regulatory agencies in their evaluation and approval processes, an important goal of clinical trials in MDS should be to prolong patient survival. Therefore, these response criteria reflected 2 sets of goals in MDS: altering the natural history of the disease and alleviating disease-related complications with improved quality of life. It is anticipated that the recommendations presented will require modification as more is learned about the molecular biology and genetics of these disorders. Until then, it is hoped these guidelines will serve to improve communication among investigators and to ensure comparability among clinical trials. (Blood. 2000;96:3671-3674)

Disease Progression↗
PubMed2000

Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Español de Citogenética Hematológica.

Recently, a consensus International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in the myelodysplastic syndromes (MDS) has been developed. However, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities for which real prognosis at present is uncertain. The main aims of this study were to evaluate in an independent series the prognostic value of the IPSS and to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in 640 patients. In univariate analyses, cases with single 1q abnormalities experienced poor survival, whereas those with trisomy 8 had a higher risk of acute leukaemic transformation than the remaining patients (P = 0.004 and P = 0.009 respectively). Patients with single del(12p) had a similar survival to patients with a normal karyotype and showed some trend for a better survival than other cases belonging to the IPSS intermediate-risk cytogenetic subgroup (P = 0.045). Multivariate analyses demonstrated that IPSS cytogenetic prognostic subgroup, proportion of bone marrow blasts and haemoglobin level were the main prognostic factors for survival, and the first two characteristics and platelet count were the best predictors of acute leukaemic transformation risk. A large international co-operative study should be carried out to clarify these findings.

Adult↗
PubMed2000

Graft-versus-tumour effect in non-small-cell lung cancer after allogeneic peripheral blood stem cell transplantation.

Clinical evidence of a graft-vs.-tumour effect in solid tumours after haematopoietic stem cell transplantation is lacking. We report for the first time a complete and durable regression of a stage IB non-small-cell lung carcinoma in a patient who had received an allogeneic peripheral blood haematopoietic stem cell transplant for acute myeloblastic leukaemia in first complete remission. Disappearance of the tumour coincided with development of graft-vs. -host disease. This suggests that simultaneous generation of cytotoxic T lymphocytes against lung carcinoma cells could have been responsible for the regression. This unique clinical observation broadens the possibility of using allogeneic haematopoietic stem cell transplantation in treating neoplasias lacking significant sensitivity to chemotherapy.

Biopsy↗
PubMed2000

Rapid quantitative detection of BCR-ABL transcripts in chronic myeloid leukemia patients by real-time reverse transcriptase polymerase-chain reaction using fluorescently labeled probes.

BACKGROUND AND OBJECTIVES: The limited value of qualitative reverse transcription polymerase chain-reaction (RT-PCR) for monitoring chronic myeloid leukemia (CML) patients has prompted the development of quantitative assays. We have developed a quantitative real-time PCR (QC-PCR) method in the LightCycler, based on the use of fluorescently labeled probes (HybProbes), to estimate BCR-ABL fusion gene transcripts in samples from CML patients. DESIGN AND METHODS: Fifty-two samples (45 peripheral blood, five bone marrow, and two apheresis product samples) from nine patients with CML were analyzed. Seven patients were studied at diagnosis and during follow-up after hematopoietic stem cell transplantation (HSCT), whereas two were evaluated only after HSCT. The PCR reaction was carried out in capillary tubes in a final volume of 10 microL, using 2 microL cDNA, the Mensik et al. primers, and two HybProbes. The results for BCR-ABL were normalized with reference to ABL. The PCR program is completed in only 45 min. RESULTS: The sensitivity attained allowed the detection of rearrangements at dilutions of between 5-10(-4) and 10(-5) K562 cDNA. The within-assay coefficient of variation was 11% for BCR-ABL, and 9% for ABL. A greater than 2 log reduction in the BCR-ABL/ABL ratio was evident shortly after transplantation in all allografted patients. INTERPRETATION AND CONCLUSIONS: We may conclude that the TaqMan probe technology can be easily adapted to HybProbes with equivalent results. Besides, the results of BCR-ABL quantification in the follow-up of patients clearly confirm that real-time PCR with HybProbes is a reliable and sensitive method for monitoring minimal residual leukemia after HSCT in CML patients.

Adolescent↗
PubMed1999

Liver disease as primary manifestation of multiple myeloma in a young man.

We report a 27-year-old man who presented with fatigue, moderate weight loss and progressive abdominal distension as primary manifestations of a light-chain multiple myeloma (MM). Liver scan showed an enlarged liver with multiple low attenuation areas. Liver biopsy revealed sinusoidal infiltration by small size cells identified as Kappa light chain-producing primitive plasma cells by immunohistochemistry. The patient responded to three courses of EDAP. Subsequently he received intensive therapy with busulfan/melfalan and a peripheral blood stem cell transplantation enriched for CD34+ cells from his HLA-identical brother. No acute graft-versus-host disease was detected. Now, 12 months after transplant, the patient is asymptomatic.

Adult↗
PubMed1999

Chronic myeloid leukemia with expression of ALL-type BCR/ABL transcript: a case-report and review of the literature.

CML with exclusive expression of ALL-type bcr/abl has only been rarely described. In some cases, the presence of this fusion gene has been associated to a differentiated subtype of CML that share some features with CMML, while in another case this molecular hallmark has been associated to a bad prognosis of the disease with a blast phase as clinical presentation or an early transformation to blast phase. We report a case of a 30-year-old woman who was diagnosed of CML in chronic phase in May 1989. She received treatment first with busulfan, achieving hematological remission and afterwards with interferon and Hydroxiurea. In February 1998, she was admitted at our hospital for an ABSCT. Then, molecular studies were performed. Multiplex PCR revealed the presence of a 481 bp product identified as the ela2 bcr/abl transcript and confirmed by sequencing. After 9 years from diagnosis, the patient remains in hematological remission and in good clinical condition.

Adult↗
PubMed1999

Carboplatin plus cytarabine in the treatment of high-risk acute myeloblastic leukemia.

Thirty-one patients (20 male and 11 female; median age 51 years (16-79)) with high-risk acute myeloblastic leukemia (AML) (20 refractory AML and 11 secondary AML (s-AML) (four to myelodysplastic syndrome, five to chemo/radiotherapy, one to aplastic anemia and one blastic chronic myelogenous leukemia (B-CML)) were treated with CBDCA (300 mg/m2/day x 5 days in continuous i.v. infusion) plus intermediate-dose Ara-C (500 mg/m2/day x 3 days in rapid i.v. infusion). Nine patients (29%) achieved CR (five s-AML (three myelodysplastic syndromes, one CML and one ALL) and four refractory AML) and 11 patients had resistant disease. There were 11 early deaths (35%). Median disease-free survival of the nine responders was 4 months. The main toxicity was hematological, febrile episodes took place in nearly all the patients (96%). The CBDCA plus Ara-C regimen showed an evident antileukemic activity in high-risk leukemia. However, the lack of long-term disease-free survivors shows the need for innovative postremission strategies. The high initial response rate seen in AML secondary to myelodysplastic syndromes (MDS) warrants further investigation of CBDCA in combination regimens for MDS patients.

Adolescent↗