Miguel Angel Diaz

Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results

Summary:Umbilical cord blood (CB) has been rapidly established as an alternative source of stem cells to bone marrow for allogeneic-related and unrelated hematopoietic transplantation. To date, almost 70 000 CB units are available for transplantation and more than 2000 CB transplants (CBT) have been performed, mostly in children, for the treatment of a variety of malignant and nonmalignant conditions. Considerable experience has been rapidly accumulated in this field and many aspects of CBT have been elucidated, while other questions remain unresolved. A concise review of the clinical results achieved after related and unrelated CBT is presented and discussed.

Peutz‐Jeghers syndrome with feminizing sertoli cell tumor

A case involving a 6‐year‐old boy with Peutz‐Jeghers syndrome and an unilateral feminizing Sertoli cell tumor is described. Endocrinologic studies revealed consistently high plasma and urine levels of estrogens and normal levels of testosterone and dihydrotestosterone. The increased levels of estrogens did not show changes that could be correlated with exogenous gonadotropin administration, thus indicating an autonomous nature. The histopathologic studies of nontumorous testicular tissue revealed changes in the seminiferous tubules which suggested that estrogens, directly or indirectly, may have had both stimulating and atrophying effects. It is concluded that gonadal tumors are an additional manifestation of the Peutz‐Jeghers syndrome gene in both male and female patients. Cancer 46:223–228, 1980.

Response to Rituximab-Based Therapy and Risk Factor Analysis in Epstein Barr Virus–Related Lymphoproliferative Disorder After Hematopoietic Stem Cell Transplant in Children and Adults: A Study From the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

BACKGROUND  The objective of this analysis was to investigate prognostic factors that influence the outcome of Epstein-Barr virus (EBV)-related posttransplant lymphoproliferative disorder (PTLD) after a rituximab-based treatment in the allogeneic hematopoietic stem cell transplant (HSCT) setting. METHODS  A total of 4466 allogeneic HSCTs performed between 1999 and 2011 in 19 European Group for Blood and Marrow Transplantation centers were retrospectively analyzed for PTLD, either biopsy-proven or probable disease. RESULTS  One hundred forty-four cases of PTLD were identified, indicating an overall EBV-related PTLD frequency of 3.22%, ranging from 1.16% for matched-family donor, 2.86% for mismatched family donor, 3.97% in matched unrelated donors, and 11.24% in mismatched unrelated donor recipients. In total, 69.4% patients survived PTLD. Multivariable analysis showed that a poor response of PTLD to rituximab was associated with an age ≥30 years, involvement of extralymphoid tissue, acute GVHD, and a lack of reduction of immunosuppression upon PTLD diagnosis. In the prognostic model, the PTLD mortality increased with the increasing number of factors: 0-1, 2, or 3 factors being associated with mortality of 7%, 37%, and 72%, respectively (P < .0001). Immunosuppression tapering was associated with a lower PTLD mortality (16% vs 39%), and a decrease of EBV DNAemia in peripheral blood during therapy was predictive of better survival. CONCLUSIONS  More than two-thirds of patients with EBV-related PTLD survived after rituximab-based treatment. Reduction of immunosuppression was associated with improved outcome, whereas older age, extranodal disease, and acute graft-vs-host disease predicted poor outcome.

Diferencias en la prevalencia del síndrome metabólico según las definiciones del ATP-III y la OMS

Fundamento y objetivo El objetivo del estudio fue conocer y comparar las diferencias en la prevalencia del sindrome metabolico (SM) estimada segun las definiciones del Adult Treatment Panel III the National Cholesterol Education Program (ATP-III) y de la Organizacion Mundial de la Salud (OMS). Pacientes y metodo Estudio descriptivo transversal en atencion primaria, en poblacion de 40 a 74 anos. Se estudiaron los factores de riesgo asi como cada uno de los componentes del SM, segun ambas definiciones. Resultados Estudiamos a 358 pacientes, 161 (45%) varones y 197 mujeres. La prevalencia del SM segun criterios de la OMS fue del 17,9% y segun los del ATP-III, del 23,5%. Esta prevalencia aumenta con la edad y con el indice de masa corporal. Ambas definiciones coinciden en la clasificacion en el 80% de los casos (indice de kappa = 0,38). Considerando de referencia la definicion de la OMS, el ATP-III presenta una sensibilidad del 59,4%, una especificidad del 84,4% y un valor predictivo negativo del 90,5%, y la concordancia mayor en mujeres y en pacientes mayores de 60 anos. Conclusiones La prevalencia del SM es menor con los criterios de la OMS. La concordancia entre los criterios de la OMS y los del ATP III es escasa. La aplicacion clinica de los criterios del ATP-III en atencion primaria precisa su homologacion con estudios clinicoepidemiologicos.

Control de la presión arterial en la población hipertensa española asistida en Atención Primaria. Estudio PRESCAP 2010

BACKGROUND AND OBJECTIVE This study was aimed at determining the degree of blood pressure (BP) control in hypertensive patients attended in primary care (PC) settings. PATIENTS AND METHOD Cross-sectional, multicenter study. Hypertensive patients ≥18 years under antihypertensive treatment attended in Spanish PC settings were included. BP control was regarded as optimum when BP values were <140/90mmHg in general population and <130/80mmHg in patients with diabetes, chronic renal disease or cardiovascular disease. BP control was also calculated for all patients when it was <140/90mmHg. RESULTS A total of 12,961 hypertensive patients (52.0% women) with a mean age of 66.3 (±11.4) years were included. A percentage of 46.3 (95% CI: 45.4-47.1) presented good systolic BP and diastolic BP control; 61.1% (IC 95%: 60.2-61.9) of patients presented good BP control<140/90. A percentage of 63.6% was treated with combination therapy (44.1% with 2 drugs, 19.5% with 3 or more). BP control was significantly higher in evening measurements (50.4%) than in morning measurements (45.1%), and in patients who had taken the treatment before the visit (47.9%) compared with those who had not (30.5%). Factors such as not taking the medication before the visit, heavy alcohol consumption and dyslipemia were the risk factors mostly associated with a poor BP control (P<.001). CONCLUSIONS Five out of 10 hypertensive patients treated in PC settings have an optimal BP control. The degree of control of arterial hypertension has improved with respect to the PRESCAP 2006 study.

Risk of complications during hematopoietic stem cell collection in pediatric sibling donors: a prospective European Group for Blood and Marrow Transplantation Pediatric Diseases Working Party study.

We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis. We conclude that PBSC and BM collection are safe procedures in children.

Increasing incidence of invasive aspergillosis in pediatric hematology oncology patients over the last decade: a retrospective single centre study.

There is scanty information about invasive aspergillosis (IA) in the pediatric population. A review of IA at Hospital Infantil Universitario Niño Jesús between 1996 and 2006 was undertaken to analyze incidence, risk factors, and treatment response. Twenty patients were diagnosed with probable or proven IA during the study period, with a cumulative incidence of 1.96%. Incidence was higher in hematopoietic stem cell transplantation (HSCT) recipients: 2.26% (3.5% in allogeneic HSCT and 1.2% in autologous HSCT). A significative increase in IA incidence was observed along the study period (P=0.013), although this increase did not reach signification if only proven cases were compared (P=0.058). Most patients presented multiple risk factors for IA (87% more than 1, and 47% more than 3). The most frequently described risk factor was chemotherapy (90%), after by long-term neutropenia (90%), and corticotherapy (75%). Main locations of the infection were pulmonary (8 patients), cutaneous (3 patients) and intestinal (3 patients). Six patients presented disseminated IA. Initial response to treatment was 55%, although 3 of these cases had a subsequent episode. Global antifungal response, at the end of the follow-up, was 45%. IA-related mortality was 55%. Global mortality was 90%. Only 2 patients (isolated cutaneous IA cases) survived. Seven patients died due to their underlying malignant disease without active fungal disease. Incidence of IA in oncology children is increasing, and in adults. In our experience, IA is a marker of poor outcome even for patients who initially respond to antifungal treatment.

High Survival Rate in Infant Acute Leukemia Treated With Early High-Dose Chemotherapy and Stem-Cell Support

PURPOSE Infants with acute leukemia have a poor prognosis when treated with conventional chemotherapy. It is still unknown if stem-cell transplantation (SCT) can improve the outcome of these patients. In the present study, we review our experience with SCT in infant acute leukemia to clarify this issue. PATIENTS AND METHODS We report the results of 26 infants who were submitted to a SCT for acute leukemia. There were 15 cases of acute myeloid leukemia and 10 cases of acute lymphoid leukemia. One patient had a bilineal leukemia. Twenty-two patients were in their first complete response (CR1), three were in their second CR, and one was in relapse. Eight patients were submitted to allogeneic SCT, and 18 underwent autologous SCT. RESULTS With a median follow-up of 67 months, the 5-year overall survival and disease-free survival (DFS) are 64% (SE = 9%) and 63% (SE = 10%), respectively. Autologous and allogeneic SCT offered similar outcome. There was not any transplant-related mortality, and all deaths were caused by relapse in the first 6 months after SCT. In multivariate analysis, the single factor associated with better DFS was an interval between CR1 and SCT of less than 4 months (P: <.025). CONCLUSION SCT is a valid option in the treatment of infant acute leukemia, and it may overcome the high risk of relapse with conventional chemotherapy showing very reduced toxicity. This study suggests that SCT should be performed in CR1 in the early phase of the disease.

Transient donor cell-derived myelodysplastic syndrome with monosomy 7 after unrelated cord blood transplantation

Abstract:  Donor cell leukaemia or myelodysplastic syndromes are extremely rare complications that have been observed not only after haematopoietic transplantation with progenitor cells harvested from bone marrow and peripheral blood, but also after cord blood transplantation. We describe the early onset of monosomy 7 in donor cells after cord blood transplantation in a patient diagnosed with myelodysplastic syndrome 3 months after transplantation. Fluorescent in situ hybridisation analysis performed in a cryopreserved aliquot of the cord blood showed 2.5% of nuclei with monosomy 7. The cord blood donor was studied and he showed neither peripheral blood cytopenias nor cytological or cytogenetic features of myelodysplasia. The cell blood counts (CBC) of the girl have improved over 2 yr while decreasing the percentage of monosomic cells. The monosomic clone has finally disappeared and the CBC are finally normal. This case of transient monosomy 7 started very early after engraftment emphasises the relevance of clonal instability of specific progenitor cells in the early engraftment, and host immune status, in cytogenetic abnormalities founded in donor cell‐derived MDS and acute leukaemia. Moreover, the clinical follow‐up of this patient, recommends a more conservative treatment for this clonal disease early developed after transplantation.

Risk score for pediatric intensive care unit admission in children undergoing hematopoietic stem cell transplantation and analysis of predictive factors for survival.

The authors retrospectively analyzed postransplantation events in 198 children who underwent hematopoietic stem cell transplantation (HSCT) between 1998 and 2002 to obtain a risk score for pediatric intensive care unit (PICU) admission and to ascertain variables predicting a poor outcome. Thirty-six patients (18%) were admitted to the PICU. Median age was 9 years (range 1-18). On univariate analysis, variables significantly associated with PICU admission were male gender (P = 0.01), more than first complete remission (P = 0.003), allogeneic transplantation (P = 0.001), engraftment syndrome (P = 0.03), and acute graft-versus-host disease grade of at least two (P = 0.05). According to this, patients were divided in two levels of risk (low and high), with a respective probability of PICU admission of 8.8 ± 2.2% and 63.8 ± 8.8% (P < 0.0001). Seventeen (47%) patients were discharged from the PICU. The probability of event-free survival after PICU admission at 3 years was 24.2 ± 7%. On univariate analysis, variables with a negative impact on event-free survival were type of transplantation, inotropic support, a C-reactive protein level of at least 10 mg/dL, and a high O-PRISM score. On multivariate analysis, the only variable that influenced event-free survival was the O-PRISM score (≤10 points, 54.6 ± 15.3%; >10 points, 8.6 ± 5.8%; P = 0.007). In conclusion, the risk of PICU admission may be easily estimated using simple variables. A high O-PRISM score at the time of PICU admission predicts a dismal outcome.