BACKGROUND AND PURPOSE Outcomes following hematopoietic stem cell transplantation for higher-risk childhood-onset cerebral adrenoleukodystrophy are variable. We explored whether a brain MRI gadolinium intensity scoring system improves prediction of neurologic outcome. METHODS A four-point scale of gadolinium intensity relative to the choroid plexus was developed: 0 = no enhancement; 1 = hypo-intense; 2 = iso-intense; 3 = hyper-intense. The scale’s inter-observer concordance was assessed on 30 randomly chosen studies. Scores were generated for 64 evaluable patients and compared with cerebrospinal fluid chitotriosidase levels, a known inflammatory marker correlating with outcomes following transplant. For 25 evaluable higher-risk patients (Loes ≥ 10), the gadolinium intensity score was compared with longer-term post-transplant clinical change. RESULTS The gadolinium intensity scoring system showed good inter-observer reproducibility (kappa = 0.72). Of 64 evaluable boys, the score positively correlated with average concomitant cerebrospinal fluid chitotriosidase activity in ng/mL/hr: (0), 2,717, n=5; (1), 3,218, n=13; (2), 6,497, n=23; and (3), 12,030, n=23 (p < 0.01). For 25 evaluable higher-risk patients, more intense pre-transplant brain MRI gadolinium enhancement predicted greater average loss on the adrenoleukodystrophy neurologic function scale following transplant: (0/1), ΔNFS = 4.3, n = 7; (2/3), ΔNFS = 10.4, n = 18 (p = 0.05). CONCLUSION Gadolinium enhancement intensity on brain MRI can be scored simply and reproducibly for cerebral adrenoleukodystrophy. Enhancement score significantly correlates with chitotriosidase. In boys with higher-risk cerebral disease (Loes ≥ 10), enhancement score itself predicts neurologic outcome following treatment. Such data may help to guide treatment decisions for clinicians and families.

The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian Society of Bone Marrow Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.

The results of hematopoietic stem cell transplant (HSCT) for primary immunodeficiency diseases (PID) have been improving over time. Unfortunately, developing countries do not experience the same results. This first report of Brazilian experience of HSCT for PID describes the development and results in the field. We included data from transplants in 221 patients, performed at 11 centers which participated in the Brazilian collaborative group, from July 1990 to December 2015. The majority of transplants were concentrated in one center (n = 123). The median age at HSCT was 22 months, and the most common diseases were severe combined immunodeficiency (SCID) (n = 67) and Wiskott-Aldrich syndrome (WAS) (n = 67). Only 15 patients received unconditioned transplants. Cumulative incidence of GVHD grades II to IV was 23%, and GVHD grades III to IV was 10%. The 5-year overall survival was 71.6%. WAS patients had better survival compared to other diseases. Most deaths (n = 53) occurred in the first year after transplantation mainly due to infection (55%) and GVHD (13%). Although transplant for PID patients in Brazil has evolved since its beginning, we still face some challenges like delayed diagnosis and referral, severe infections before transplant, a limited number of transplant centers with expertise, and resources for more advanced techniques. Measures like newborn screening for SCID may hasten the diagnosis and ameliorate patients' conditions at the moment of transplant.