Donor source and post-transplantation cyclophosphamide influence outcome in allogeneic stem cell transplantation for GATA2 deficiency.

GATA2 deficiency was described in 2011, and shortly thereafter allogeneic hematopoietic stem cell transplantation (HSCT) was shown to reverse the hematologic disease phenotype. However, there remain major unanswered questions regarding the type of conditioning regimen, type of donors, and graft-versus-host disease (GVHD) prophylaxis. We report 59 patients with GATA2 mutations undergoing HSCT at National Institutes of Health between 2013 and 2020. Primary endpoints were engraftment, reverse of the clinical phenotype, secondary endpoints were overall survival (OS), event-free survival (EFS), and the incidence of acute and chronic GVHD. The OS and EFS at 4 years were 85·1% and 82·1% respectively. Ninety-six percent of surviving patients had reversal of the hematologic disease phenotype by one-year post-transplant. Incidence of grade III-IV aGVHD in matched related donor (MRD) and matched unrelated donor recipients (URD) patients receiving Tacrolimus/Methotrexate for GVHD prophylaxis was 32%. In contrast, in the MRD and URD who received post-transplant cyclophosphamide (PT/Cy), no patient developed grade III-IV aGVHD. Six percent of haploidentical related donor (HRD) recipients developed grade III-IV aGVHD. In summary, a busulfan-based HSCT regimen in GATA2 deficiency reverses the hematologic disease phenotype, and the use of PT/Cy reduced the risk of both aGVHD and cGVHD.

Prospective Study of Gastrointestinal Symptoms in School Children of South America.

OBJECTIVES: The aim of the study was to establish the prevalence of abdominal pain (AP) in school children in Pasto (Colombia) and determine the effect of AP on their daily activities; and compare the prevalence of AP and other gastrointestinal symptoms between school children from Pasto and Chicago. METHODS: Fourth- and fifth-grade students from a public school and a private school in Colombia were invited to participate in a prospective study using the same methods and questionnaires (Spanish version) as a previous study conducted in Chicago schools. Children completed weekly confidential surveys for 8 consecutive weeks. RESULTS: A total of 332 children participated in the study (40% girls, mean age 9.97 years, median 10, range 8-12 years): public school (288), private school (44). A total of 2425 surveys were analyzed. Out of 2656 possible weekly surveys (332 children × 8 weeks), 91.3% were completed. Overall weekly prevalence of gastrointestinal symptoms: AP (39%), nausea (29.5%), constipation (14%), diarrhea (10.5%), vomiting (9%). Children with AP reported interference with activities: gym (21.9%), school (17.3%), difficulty sleeping (13.7%), and social activities (12.6%). Out of all children, 8.4% sought medical attention for AP during the study period. CONCLUSIONS: Gastrointestinal symptoms are common in school-aged children in Colombia and interfere with both daily activities and school attendance. The prevalence of AP, diarrhea, and vomiting found in the present study was similar to published prevalence of American children using similar methods.

A strategy to improve treatment-related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays.

BACKGROUND: Treatment-related mortality and abandonment of therapy are major barriers to successful treatment of childhood acute lymphoblastic leukemia (ALL) in the developing world. PROCEDURE: A collaboration was undertaken between Instituto Nacional de Cancerologia (Bogota, Colombia), which serves a poor patient population in an upper-middle income country, and Dana-Farber/Boston Children's Cancer and Blood Disorders Center (Boston, USA). Several interventions aimed at reducing toxic deaths and abandonment were implemented, including a reduced-intensity treatment regimen and a psychosocial effort targeting abandonment. We performed a cohort study to assess impact. RESULTS: The Study Population comprised 99 children with ALL diagnosed between 2007 and 2010, and the Historic Cohort comprised 181 children treated prior to the study interventions (1995-2004). Significant improvements were achieved in the rate of deaths in complete remission (13% to 3%; P = 0.005), abandonment (32% to 9%; P < 0.001), and event-free survival with abandonment considered an event (47% to 65% at 2 years; P = 0.016). However, relapse rate did not improve. Medically unnecessary treatment delays were common, and landmark analysis revealed that initiating the PIII phase of therapy ≥4 weeks delayed predicted markedly inferior disease-free survival (P = 0.016). Conversely, patients who received therapy without excessive delays had outcomes approaching those achieved in high-income countries. CONCLUSIONS: Implementation of a twinning program was followed by reductions in abandonment and toxic deaths, but relapse rate did not improve. Inappropriate treatment delays were common and strongly predicted treatment failure. These findings highlight the importance of adherence to treatment schedule for effective therapy of ALL.

Construct validity of the pediatric Rome III criteria.

OBJECTIVES: Functional gastrointestinal disorders (FGIDs) are common. The diagnosis of FGIDs is based on the Rome criteria, a symptom-based diagnostic classification established by expert consensus. There is little evidence of validity for the pediatric Rome III criteria. The construct validity of the criteria, an overarching term that incorporates other forms of validity, has never been assessed. We assessed the construct validity of the Rome III criteria. METHODS: Children from 2 schools in Colombia completed the Questionnaire on Pediatric Gastrointestinal Symptoms at baseline and weekly questionnaires of somatic symptoms and disability for 8 weeks (presence and intensity of gastrointestinal symptoms, nongastrointestinal symptoms, impact on daily activities). A total of 255 children completed at least 6 weekly surveys (2041 surveys). RESULTS: At baseline, 27.8% children were diagnosed as having an FGID. Prevalence of nausea (Δ 7.8%, 95% confidence interval [CI] 4.46-11.14), constipation (Δ 4.39%, 95% CI 1.79-6.99), diarrhea (Δ 6.69%, 95% CI 3.25-10.13), headache (Δ 7.4%, 95% CI 3.51-11.09), chest pain (Δ 9.04%, 95% CI 5.20-12.88), and limb pain (Δ 4.07%, 95% CI 1.76-6.37) and intensity of nausea (Δ 0.23, 95% CI 0.127-0.333), diarrhea (Δ 0.30, 95% CI 0.211-0.389), abdominal pain (Δ 0.18, 95% CI 0.069-0.291), headache (Δ 0.17, 95% CI 0.091-0.249), and limb pain (Δ 0.30, 95% CI 0.084-0.516) were higher in children with FGIDs (P < 0.001). Children with FGIDs had greater interference with daily activities (P < 0.001). CONCLUSIONS: Children with a Rome III diagnosis had significantly more gastrointestinal and nongastrointestinal complaints, and greater intensity of symptoms and disability than children without an FGID diagnosis. The study suggests that the Rome III pediatric criteria have adequate construct validity.

MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients.

Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan® ) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care.

Prevalence of functional gastrointestinal disorders in Colombian school children.

OBJECTIVES: To determine prevalence for functional gastrointestinal disorders (FGIDs) in Colombian school children using the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version (QPGS-III) and to determine possible risk factors. STUDY DESIGN: The QPGS-III was translated into Spanish then reverse translated by a team of bilingual physicians. Focus groups of Colombian children were conducted to assure understanding of the Spanish version. Children at 1 public school and 2 private schools in Pasto, Colombia were invited to participate in a prevalence study using the translated questionnaire. RESULTS: A total of 373 children (95 private school, 278 public school), with mean age 9.9 years completed the QPGS-III. Twenty-nine percent of children were diagnosed with FGIDs. FGIDs were more common in females (OR, 1.63; 95% CI, 1.04-2.56). Functional constipation (14%) was the most common FGID. Irritable bowel syndrome was the most common abdominal pain-related FGID (5.4%). Abdominal migraine (1%) and cyclic vomiting syndrome (0.3%) were the least common FGIDs. CONCLUSION: FGIDs are common in Colombian school children.