Ghadir Sasa

Outcomes after Allogeneic Transplant in Patients with Wiskott-Aldrich Syndrome

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Currently, hematopoietic stem cell transplantation (HSCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, even after fully myeloablative preparative regimens, mixed donor chimerism is a potential concern. We performed a retrospective chart review of 12 children who underwent allogeneic HSCT for WAS to report our experience. The median age at transplant was 10.5 months (range, 3 to 39). The median nucleated cell dose from the marrow was 4.55 × 109/kg (range, .3 to 7.9). The median times to neutrophil and platelet engraftment were 19 days (range, 13 to 27) and 18.5 days (range, 12 to 31), respectively. The rate of overall survival was 92% with median follow-up of 67 months (range, 3 to 146). Two patients developed grade IV acute graft-versus-host disease, and 1 died on day +99. Five of 12 patients (42%) had mixed donor chimerism (range, 12% to 85%) at day +180. None of the pretransplant patient parameters was predictive of mixed chimerism. Nonetheless, of these 5 patients, 2 had normalization of the platelet count despite the mixed chimerism, 2 had full donor chimerism after receiving a second transplant with the same donor, and 1 remains transfusion dependent awaiting a second transplant. Hence, even with a significant rate of mixed chimerism, HSCT provides substantial benefit to WAS patients, with excellent overall survival.

Allogeneic hematopoietic cell transplant following crizotinib monotherapy for relapsed/refractory anaplastic large cell lymphoma

Relapsed ALK‐positive ALCL often is responsive to CRZ monotherapy. The subsequent role of allogeneic HCT after achieving second remission is poorly understood. We report 6 children who underwent allogeneic HCT for relapsed ALCL after CRZ. Age at transplant ranged from 10.7 to 22.6 years. Follow‐up ranged from 0.9 to 4.5 years. All patients engrafted. Three of 4 patients that received a reduced‐toxicity conditioning regimen containing fludarabine, alemtuzumab, and low‐dose irradiation showed progressive mixed chimerism. Five patients remain in remission. One patient developed isolated CNS relapse 3.6 years after HCT despite a lack of previous CNS involvement. No acute transplant‐related complications were experienced. One patient developed chronic renal disease secondary to transplant‐associated microangiopathy and one patient chronic GVHD secondary to DLI. Ultimately, allogeneic HCT appears safe and potentially curative after remission induction with CRZ. The role of conditioning therapy, ablative or reduced intensity, remains uncertain for patients’ post‐CRZ monotherapy, and further studies may be warranted.

High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease

There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.

Current Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphocytic Leukemia: Success, Failure and Future Perspectives—A Single-Center Experience, 2008 to 2016

Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T cell depletion used and, consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes among different donor types. One hundred and twenty-four pediatric patients underwent HSCT from a matched sibling donor (MSD; n = 48), an unrelated matched donor (UMD; n = 56), or a haploidentical donor (n = 20). We observed a similar 3-year event-free survival (EFS) for MSD recipients (of .64) and for UMD recipients (.62), but a significantly lower EFS for recipients of haploidentical transplants (.35; P = .01). Relapse was the main cause of HSCT failure and was significantly higher in the haploidentical donor group (.47 versus .19 for MSD and .24 for UMD; P = .02). Treatment-related mortality was evenly distributed among the donor groups (.17, .16, and .15 for the MSD, UMD, and haploidentical groups, respectively). Rates of infection-related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era, and this effect is most evident in recipients of haploidentical donor grafts. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high-risk patients.Abstract Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed Acute Lymphoblastic Leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T-cell depletion used, and consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes between different donor types. One hundred and twenty four pediatric patients underwent HSCTs from either matched sibling (MSD, N=48), unrelated matched (UMD, N=56) or haplo-identical (N=20) donors. We observed a similar 3 years EFS for MSD recipients (of 0.64) and for UMD recipients (0.62) while EFS was significantly lower for recipients of haplo-identical transplants (0.35, P=0.01). Relapse was the main cause of HSCT failure and was significantly higher in the haplo-identical donor group (0.47 vs 0.19 and 0.24 for MSD and UMD, respectively P=0.02). Treatment related mortality (TRM) was evenly distributed among the donor groups (0.17, 0.16 and 0.15 for the MSD, UMD and haplo-identical groups, respectively). Rates of infectious related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era and this effect is most evident in recipients of haplo-identical donors. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high risk patients.