Clinical outcome after sex-mismatched allogeneic stem cell transplantation from human lymphocyte antigen-identical sibling donors: influence of stem cell source.
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Adolescent↗
Biomedical subjects
D Caballero
Publications and source records attributed to D Caballero.
Oral beclomethasone dipropionate for the treatment of gastrointestinal acute graft-versus-host disease (GVHD).
Acute graft-versus-host disease (aGVHD) remains one of the most severe complications after allogeneic transplantation; in particular, the presence of gut involvement has been related to increased mortality and poorer response. The use of systemic steroids remains the standard for first-line treatment despite its severe secondary effects. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with low absorption, thereby avoiding many of the deleterious side effects associated with systemic steroids. In the present study we analyzed the efficacy of BDP in a series of 26 patients who were diagnosed with grade 1 and 2 gastrointestinal aGVHD. Twenty patients (77%) responded to BDP treatment, 17 (65.5%) reached complete remission (CR), and 3 (11.5%) showed partial response. Among those patients who reached CR, 5 relapsed, although 1 of them reached second CR after a second course of BDP; therefore, 13 (50%) of the 26 patients did not require systemic steroids to treat gastrointestinal aGVHD. CR rates in those showing gastrointestinal symptoms were 68% for patients with persistent nausea, 50% for those with vomiting, and 54% for those with diarrhea (P=.2). No patient included in the study developed any symptom related to adrenal axis suppression. Thirteen patients (50%) developed >or=1 infectious episode during the first 100 days after transplantation. Transplant-related mortality was 0% at 100 days, and overall transplant-related mortality was 30%, with only 2 patients dying due to infectious complications. Therefore, our study shows that monotherapy with oral BDP is an effective initial therapeutic approach for mild to moderate intestinal GVHD, which avoids complications related to systemic steroids.
Administration, Oral↗
Vincristine is an effective therapeutic approach for transplantation-associated thrombotic microangiopathy.
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Adolescent↗
Reduced-intensity conditioning allogeneic transplantation is associated with a high incidence of extramedullary relapses in multiple myeloma patients.
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Bone Marrow Transplantation↗
Long-term outcome of allogeneic PBSC transplantation in pediatric patients with hematological malignancies: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) and the Spanish Group for Allogeneic Peripheral Blood Transplantation (GETH).
We analyzed the clinical outcome in 90 children undergoing allogeneic PBSC transplantation from HLA-identical relative for leukemia. GvHD prophylaxis was CsA+ methotrexate in 50 and CsA+/-steroids in 40. Median CD34+ cells infused were 6 x 10(6)/kg (range, 1.4-32). Median follow-up was 60 months (range, 6-115). CI of transplant-related mortality (TRM) was 18.4+/-4%. On multivariate analysis, high Lansky score (>80) at transplantation was associated with lower TRM (HR, 0.9; P<0.0002). Relapse incidence (RI) was 33.6+/-6%. On multivariate analysis, high Lansky score at transplantation and cGvHD were associated with lower RI (HR, 0.04; P<0.0005 and HR, 0.23; P<0.03, respectively). Disease-free survival (DFS) was 57.8+/-5%. Disease status at transplantation (HR, 0.33; P<0.02), steroid treatment at day +90 (HR, 5.61; P<0.005) and cGvHD (HR, 0.23; P<0.005) had a significant impact on DFS in multivariate analysis. CI of cGvHD was 63.7+/-7%. Patients with cGvHD had better DFS (65+/-5%) because of lower RI (15.7+/-6%) and similar TRM (27.4+/-4%). These data suggest acceptable long-term outcomes after allogeneic PBSC transplantation in children despite the high incidence of cGvHD. These patients had a lower risk of relapse and a better DFS.
Adolescent↗
Successful treatment of rhinocerebral zygomycosis with a combination of caspofungin and liposomal amphotericin B.
Genera of the order Mucorales (Rhizopus, Mucor, Rhizomucor, Absidia, Apophysomyces, Cunninghamella, and Saksenaea) cause an angioinvasive infection called zygomycosis. Mortality rates can approach 100% depending on the patient's underlying disease and form of zygomycosis. We report here on the unusual case of a patient with acute myelogenous leukemia and zygomycosis unresponsive to monotherapy with liposomal amphotericin B, who responded favorably following the addition of the echinocandin caspofungin acetate.
Amphotericin B↗
Antibiotic prophylaxis with meropenem after allogeneic stem cell transplantation.
In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.
Acute Disease↗
Risk assessment and outcome of chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell transplantation in pediatric patients.
We retrospectively evaluated the incidence, risk factors for chronic graft-versus-host disease (cGvHD) and outcome in 80 pediatric patients (36 male) (median age 13 years) who underwent allogeneic peripheral blood progenitor cell transplantation. Patients were grafted from an HLA-identical sibling after myeloablative conditioning (total body irradiation (TBI) based 52; non-TBI 28). GvHD prophylaxis used were: cyclosporin A (CsA)+ short methotrexate (MTX) in 52 and CsA+/-prednisone in 28. The median number of CD34+ cells infused were 5.8 x 10(6)/kg (range: 1.4-32.8). The median follow-up was 24 months (range: 3-94). In all, 28 patients had cGvHD (confidence interval (CI): 54.2+/-10%). Factors that were significant on univariate analysis were diagnosis (P=0.03) and GvHD prophylaxis administered (P=0.04). On multivariate analysis, only GvHD prophylaxis used was associated with a significant risk of cGvHD (hazard ratio (HR): 3.94; 95% CI: 1.41-10.91, P=0.009). The CI of cGvHD for patients receiving CsA+MTX was 40.9+/-12 vs 76.5+/-18% for patients who did not (P=0.03). The probability of relapse was 36+/-6% for all patients (12.5+/-8% for patients with cGvHD vs 47.9+/-8% without cGvHD). The probability of disease-free survival was better for patients with cGvHD (69.9+/-10 vs 37.9+/-7%; HR: 3.59, 95% CI: 1.47-5.56; P=0.001). Our data suggest that the GvHD prophylaxis used is the most relevant predictor of cGvHD. Patients with cGvHD had a lower risk of relapse and a better survival.
Adolescent↗
Lenograstim after autologous peripheral blood progenitor cell transplantation: results of a double-blind, randomized trial.
A phase III, randomized, double-blind, placebo-controlled, multi-center trial was conducted in order to compare the incidence of microbiologically defined infections occurring after high-dose chemotherapy (HDT) and ASCT in 98 patients given lenograstim (Granocyte) and 94 patients given placebo after transplantation. Hematopoietic recovery, the use of i.v. antibiotics, the numbers of red blood cell and platelet transfusions, the days spent in hospital, and the days on parenteral nutrition were also compared. The incidence of infections until neutrophil recovery was significantly less in patients who received lenograstim after HDT and ASCT as compared to patients who received placebo (66 of 98 vs 86 of 94 patients, P<0.001). Lenograstim also significantly reduced the use of i.v. antibiotics (P<0.001) and the median duration of i.v. antibiotic treatment (8 days vs 10 days, P=0.04), improved neutrophil recovery (absolute neutrophil count >0.5 x 10(9)/l: 11 days vs 15 days, P<0.001) and reduced the number of days spent in hospital (15 days vs 17 days, P<0.001). The administration of lenograstim after HDT and ASCT significantly reduces the incidence of microbiologically defined infections until neutrophil recovery. It also leads to less use of antibiotics and earlier discharge from hospital.
Adjuvants, Immunologic↗
Predicting survival for myeloid leukemia after HLA-identical sibling donor allogeneic stem cell transplantation.
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Disease-Free Survival↗
Predicting survival for myeloid leukemia after HLA-identical sibling donor allogeneic stem cell transplantation.
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Acute Disease↗
Graft vs. host disease and graft vs. myeloma effect after non-myeloablative allogeneic transplantation.
For many years progress in event free and overall survival in patients diagnosed with multiple myeloma have been modest, however recently newer therapeutic options have become available and, for a small but increasing subset of patients, an "operational cure" can be offered. Although autologous transplantation is associated with a prolongation in event free and overall survival as compared to conventional chemotherapy, there is no plateau in the survival curves. By contrast, the use of allogeneic hematopoietic stem cells provides a tumor-free stem cell source and graft-vs.-myeloma activity leading to a higher frequency of long term survivors in molecular remission. Unfortunately, allogeneic transplantation has been associated with high transplant-related mortality (TRM). Non-myeloablative or reduced intensity conditioning (RIC) regimens, designed to be immunosuppressive rather than myeloablative, in an effort to reduce the toxicity and TRM associated with high dose chemotherapy, but maintaining the GVM effect, have been developed showing up to 90% overall response rate and low TRM. Interestingly, in a significant proportion of patients disease response is preceded by GVHD, suggesting a clear relationship between GVHD and graft vs. myeloma effect. Nevertheless these patients are at risk of developing life threatening complications and, on the contrary, some patients who reach disease control after GVHD and respond to GVHD therapy may finally relapse. Thus, efforts to separate GVM and GVHD are still required in order to improve the outcome of myeloma patients receiving allogeneic transplantation.
Graft vs Host Disease↗
Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning.
We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n=40) or busulphan (n=28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (P<0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression post-transplant was the development of chronic extensive GVHD (P<0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.
Adult↗
Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation.
Since graft-versus-leukemia (GVL) is the main weapon for disease eradication after reduced intensity conditioning (RIC) allogeneic SCT, the availability of sensitive and specific techniques to monitor changes in tumor load after transplant are especially helpful. These minimal residual disease techniques would allow an early intervention in the event of low tumor burden, for which immunotherapy is highly effective. Some authors have found an association between persistence of MRD, mixed chimerism and risk of relapse. Nevertheless, data from the literature remain contradictory and further correlations should be established, especially in RIC transplants. In this study we have analyzed the impact of MRD and chimerism monitoring on the outcome of 34 patients undergoing RIC allogeneic SCT who were considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions. At day +100 25 (75%) patients reached complete remission (CR), there were five (15%) partial responses and three patients progressed. Incidence of grade 2-4 aGVHD and extensive cGVHD were 35% and 58%, respectively. Sixteen percent of patients developing aGVHD relapsed as compared to 47% in those without aGVHD (P = 0.03) and also 10% of patients developing cGVHD relapsed as compared to 50% relapses in those without cGHVD (P = 0.03). Four patients (12%) died due to early (n = 1) and late (n = 3) transplant-related mortality. After a median follow-up of 15 months, 24 out of the 34 patients remain alive. Projected overall survival and disease-free survival at 3 years are 68% and 63%, respectively. Early chimerism analysis showed 67% of patients with complete chimerism (CC) in bone marrow (BM), 86% in peripheral blood (PB), 89% in granulocytes and 68% in T lymphocytes. On day +100, these figures were 68%, 79%, 90% and 73%, respectively, and on day +180 there were 83% patients with CC in BM, 100% in PB, 100% in granulocytes and 100% in T lymphocytes. We observed a trend to a higher incidence of relapse in patients with mixed chimerism (MC) as compared to patients with CC. MRD monitoring by flow cytometry and/or RT-PCR analysis was performed in 23 patients. MRD assessment on days +21 to +56 after transplant allowed identification of patients at risk of relapse. In this sense, seven out of 12 patients (58.3%) who had positive MRD on days +21 to +56 relapsed as compared to none out of 11 patients who had negative MRD (P = 0.002). Of the seven patients with criteria to monitor MRD who relapsed after transplant, all but one remained MRD positive until relapse. By contrast, 10 patients remained MRD negative and all of them are in continuous CR. In nine additional patients, persistence of MRD or mixed chimerism was observed after transplant and withdrawal of cyclosporin with or without DLI was performed. Only two out of these nine patients relapsed. MRD clearance was preceded by CC and GVHD. In conclusion, in our study we found that RIC allogeneic transplantation can be used in patients considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions with both low toxicity and low transplant-related mortality. Simultaneous studies of both chimerism and MRD are a useful tool in order to predict risk of relapse in patients undergoing RIC transplants and so can be helpful for individualizing treatment strategies after transplant.
Adult↗
Refractive acoustic devices for airborne sound.
We show that a sonic crystal made of periodic distributions of rigid cylinders in air acts as a new material which allows the construction of refractive acoustic devices for airborne sound. It is demonstrated that, in the long-wave regime, the crystal has low impedance and the sound is transmitted at subsonic velocities. Here, the fabrication and characterization of a convergent lens are presented. Also, an example of a Fabry-Perot interferometer based on this crystal is analyzed. It is concluded that refractive devices based on sonic crystals behave in a manner similar to that of optical systems.
Journal Article↗
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↗
Cidofovir treatment of human polyomavirus-associated acute haemorrhagic cystitis.
We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.
Adolescent↗
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↗