Background
Despite the increasing performance of allogeneic hematopoietic cell transplantation over the last decades, graft‐versus‐host disease (GVHD) remains the main cause of morbidity and ...mortality. The efficacy of ruxolitinib against GVHD has been demonstrated in adult studies; however, very few studies have been conducted in children.
Procedure
This study aimed to evaluate the efficacy of ruxolitinib in 29 children with steroid‐refractory acute or chronic GVHD. Twenty‐five (87%) patients received at least three different immune modulator agents, including methylprednisolone, before initiating ruxolitinib.
Results
All grade 2 acute GVHD patients completely responded to ruxolitinib treatment; 82% of high‐grade (3‐4) acute GVHD patients and 80% of chronic GVHD (moderate‐severe) patients had at least a partial response. Of seven patients with bronchiolitis obliterans, five had a partial response after ruxolitinib. Of 29 patients, 22 were administered steroids at any time in the first month of acute GVHD or the first three months of chronic GVHD during ruxolitinib usage, which was significantly tapered by the end of the observation period.
Conclusion
Steroid‐refractory acute and chronic pediatric GVHD patients treated with ruxolitinib had a high overall response rate, with the additional benefit of steroid sparing.
EBV-associated lymphoproliferative disorders (LPDs) are common in hematopoietic stem cell transplantation (HSCT) with T-cell-depleted grafts, but are extremely rare in HSCT patients with ...T-cell-replete grafts with post-transplant cyclophosphamide (PTCy). Here we present the cases of two pediatric patients who developed EBV-related LPD after T-cell-replete haplo-HSCT with PTCy. One of these is the first reported case of EBV-positive mucocutaneous ulcer (EBVMCU) developing after PTCy. EBV-related diseases are rare in T-cell-replete haplo-HSCT patients with PTCy. However, in patients with risk factors, it is reasonable to screen for EBV viremia for LPD.
Immune reconstitution inflammatory syndrome (IRIS) is a clinical condition emerging after immune recovery of an immunocompromised status, mostly in human immunodeficiency virus infected patients but ...also in several other settings, such as the recovery from the severe combined immunodeficiency status after hematopoietic stem cell transplantation. Herein, we report a patient transplanted for severe combined immunodeficiency who developed IRIS for 2 times, namely shortly after transplantation and after donor lymphocyte infusion. Pediatric transplant teams need to be aware of the previous IRIS phenomenon of BCG-adenitis while making the decision of donor lymphocyte infusions.
Deficiency of the CD40L, expressed on the surface of T lymphocytes, is caused by mutations in the glycoprotein CD40L (CD154) gene. Resulting defective humoral and cellular responses cause a clinical ...presentation that includes recurrent sinopulmonary bacterial infections, opportunistic infections, sclerosing cholangitis, neutropenia, and autoimmune manifestations. HSCT represents the only curative treatment modality. However, the therapeutic decision to use HSCT proves challenging in many cases, mainly due to the lack of a phenotype‐genotype correlation. We retrospectively reviewed patients with CD40L deficiency who were transplanted in Antalya and Göztepe MedicalPark Pediatric HSCT units from 2014 to 2019 and followed by Akdeniz University School of Medicine Department of Pediatric Immunology. The records of eight male cases, including one set of twins, were evaluated retrospectively. As two transplants each were performed on the twins, a total of ten transplants were evaluated. Conditioning regimens were predominantly based on myeloablative protocols, except for the twins, who received a non‐myeloablative regimen for their first transplantation. Median neutrophil and platelet engraftment days were 13 (range 10‐19) and 14 (range 10‐42) days, respectively. In seven of ten transplants, a CMV reactivation was developed without morbidity. None of the patients developed GVHD, except for one mild case of acute GVHD. All patients survived, and the median follow‐up was 852 days. Our data show that HSCT for patients with CD40 ligand deficiency is a potentially effective treatment for long‐term disease control.
Background
Although there are many studies on the role of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT), outcomes have often reported conflicting results because of the ...heterogeneity of the patients in the studies.
Methods
We investigated the association between VDD prior to HSCT and outcomes after HSCT in a relatively homogenous group of patients with thalassemia major (TM) who received identical treatment for TM before transplantation, and the same conditioning regimen and GVHD prophylaxis during and after transplantation. All patients, including the patients with normal vitamin D3 levels received 400 to 800 IU per day of vitamin D for the first 6 months after HSCT.
Results
Pre‐HSCT VDD increased the frequency of aGVHD after transplantation, particularly in HSCTs performed with PBSC for the stem cell source. Pre‐transplant low vitamin D3 levels had no association with transplant outcomes such as engraftment, viral infections, alloimmunization, chronic GvHD, total days of hospitalization, and success in terms of transfusion independence.
Conclusions
Low vitamin D3 levels before HSCT carry a significant risk for aGVHD. All patients with TM should be screened for VDD before HSCT, and every effort should be made to supplement vitamin D before the transplant in VDD patients.
Background
Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections. Allogeneic hematopoietic ...stem cell transplantation (HSCT) is a curative therapy for CID; however, little is known about the necessity and benefits of HSCT in patients with STK4 deficiency.
Methods
We report two siblings with STK4 deficiency transplanted from two unrelated donors with the same conditioning regimen.
Results
In the conditioning regimen, rituximab was given on Day −11 (375 mg/m2), and sirolimus was added on the same day. Busulfan was administered at a myeloablative dose (3.2 mg/kg; Days −7 to −4) with 150 mg/m2 of fludarabine (Days −7 to −3). They were transplanted with peripheral blood stem cells, and graft‐versus‐host disease (GVHD) prophylaxis was administered with 10 mg/m2 methotrexate on Days 1, 3, and 6. In addition, mycophenolate mofetil (MMF) was started on Day 1 with ongoing use of sirolimus. We did not encounter veno‐occlusive disease (VOD), high‐grade acute GVHD, or significant organ toxicity in either patient. Both patients were well at the end of the first year after HSCT with complete donor chimerism.
Conclusions
Serine/threonine kinase 4 deficiency is a disease with high mortality post‐HSCT; therefore, the conditioning regimen and GVHD prophylaxis strategies are important considerations in these patients. In our opinion, the conditioning regimen, which includes rituximab and busulfan and fludarabine (BU‐FLU), GVHD prophylaxis with sirolimus and MMF, and short‐term methotrexate, offers favorable outcomes and is well tolerated in our STK4‐deficient patients.
Objective
The selection of graft‐vs. ‐host disease (GvHD) prophylaxis is vital for the success of hematopoetic stem cell transplantation (HSCT), and calcineurin inhibitors (CNI) have been used for ...decades as the backbone of GvHD prophylaxis. The aim of this study is to analyze the results of switching cyclosporine (CSA) to tacrolimus because of acute GvHD, engraftment syndrome (ES), persistent low level of CSA, or various CSA‐associated adverse events in the first 100 days of pediatric HSCT.
Materials and Methods
This is a retrospective analysis of 192 patients who underwent allogeneic hematopoietic stem cell transplantation at Medicalpark Göztepe and Antalya Hospitals between April 2014 and May 2019 had therapy switched from CSA to tacrolimus‐based immunosuppression within 100 days of transplant.
Results
The reasons for conversion to tacrolimus were low level of CSA (n = 70), aGvHD (n = 63), CSA‐associated neurotoxicity (n = 15), CSA‐associated nephrotoxicity (n = 10), hypertension (n = 10), allergic reactions (n = 9), ES (n = 7), CSA‐associated hepatotoxicity (n = 5), and vomiting (n = 3). The median day after transplant for conversion to tacrolimus for all patients was day 20 (range 0‐100 days). Response rates to conversion were 38% for GvHD, 86% for neurotoxicity, 50% for nephrotoxicity, 60% for hepatotoxicity, 80% for hypertension, 66% for vomiting, and 57% for ES. Twenty‐nine patients (15%) experienced tacrolimus‐associated toxicities after therapy conversion to tacrolimus. Neurotoxicity emerged as posterior reversible encephalopathy syndrome (PRES), which was the most common toxicity observed after conversion (18/29 patients).
Conclusion
Our data support the quick conversion to tacrolimus in the condition of persistent low CSA levels with acceptable efficacy and safety. Although both drugs are CNI and share a very similar mechanism of action, the conversion could be preferred especially in specific organ toxicities with special attention for neurotoxicity after conversion.
DIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, ...autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile.
Background
ALD is a rare X‐linked peroxisomal metabolic disorder with many distinct phenotypes of disease that emerge on a wide scale from adrenal insufficiency to fatal cALD which progresses to a ...vegetative state within a few years. Currently, HSCT is the only treatment method known to stabilize disease progression in patients with cALD. In this study, we aim to report our HSCT experience in patients with cALD and the factors that determine the success of HSCT, as a single‐center experience.
Methods
The study cohort involves 23 boys with cALD and three patients with ALD trait and new‐onset abnormal behavior who underwent allogeneic HSCT between January 2012 and September 2019 in our transplantation center. Loes scoring, NFS, scale and MFD were performed for evaluating the severity of the cerebral disease. The study cohort was divided into two groups according to baseline NFS and Loes score: early‐stage (NFS ≤ 1 and Loes score <9) and advanced stage (NFS > 1 or Loes score ≥9).
Results
The pretransplant stage of disease impacted both OS and MFD‐free survival. The estimated OS and MFD‐free survival at 3 years in patients with advanced disease were 46.1% (95% CI 19.0–73.2) and 23.1% (95% CI 0.2–46.0), respectively, and all patients with the early disease were alive (p: .004) and MFD‐free (p < .001) at 3 years.
Conclusion
This study demonstrated that early HSCT is vital in patients with cALD. The early‐stage disease had a significant survival advantage and free from disease progression after HSCT.
Background
Post‐Cy administration for GVHD prophylaxis in unmanipulated haploidentical HSCT has resulted in improved outcomes in recent years. Studies in children are lacking and accordingly we ...present the outcomes of 62 haploidentical transplantation for high‐risk children.
Procedure
We retrospectively assessed 62 transplants in 60 patients who underwent haploidentical‐related HSCT with unmanipulated stem cells and for whom Post‐Cy was used for GVHD prophylaxis.
Results
Myeloid reconstitution was achieved on day + 30 for 57 of the 62 patients. The median follow‐up of the surviving 39 patients (63%) was 26 months, with a range of 6‐57 months. The OS and EFS at 2 years were 64.6% (52.0%‐77.2%, 95% CI) and 58.9% (46.1%‐71.7%, 95% CI), respectively. The only factor in our multivariate analysis that contributed to an inferior EFS was a poor remission status prior to HSCT (HR, 8.30; 1.08‐63.56; P = 0.041, 95% CI).
Conclusion
The results of T‐cell replete haploidentical transplantation with Post‐Cy GVHD prophylaxis in high‐risk pediatric patients are promising. However, further research is needed to determine the factors that have affect HLA compatibility for predicting the success of haploidentical transplantations.
