Purtscher‐like retinopathy: A rare presentation of hematopoietic stem cell transplant‐associated thrombotic microangiopathy

Hematopoietic stem cell transplant (HSCT)‐associated (TA) thrombotic microangiopathy (TMA) is an acquired disorder and a potentially life‐threatening complication after allogeneic HSCT. TA‐TMA causes endothelial damage and results in micro‐thrombi in capillaries and arterioles. Early detection and treatment of complications associated with TA‐TMA might improve outcomes. Purtscher‐like retinopathy (PLR) is associated with micro‐thrombi that occlude the retinal arteries and cause retinal injury. PLR has been associated with multiple entities, including HUS and TTP, but has not previously been described in the setting of TA‐TMA. Here, we describe an 18‐year‐old male who underwent a mismatched unrelated donor HSCT for relapsed acute lymphoblastic leukemia. The patient was diagnosed with TA‐TMA based on standard defined criteria. He presented with acute onset of blurred vision with findings of multiple white retinal patches, retinal hemorrhages, and macular edema, thought initially to be hypertensive retinopathy. However, on further evaluation using fluorescein angiography and optical coherence tomography, the diagnosis was determined to be PLR. The patient was treated with intravitreal steroid injections (triamcinolone acetonide) with dramatic improvement of vision. The aim of this report is to make clinicians aware of PLR as a potential ocular complication associated with TA‐TMA and that prompt intervention might reverse visual impairment.     

Haploidentical hematopoietic stem cell transplantation with post‐transplant high‐dose cyclophosphamide in high‐risk children: A single‐center study

Recently, haploidentical transplantations have been performed with unmanipulated BM or PBSC. This approach is becoming more widely adopted with the use of PTCY. However, there is limited evidence about this approach in children. We present 15 children who received 16 haploidentical HSCT with unmanipulated BM or PBSC using PTCY for GVHD prophylaxis. Post‐transplant CY(50 mg/kg IV) was given on the third and fifth day, and CsA or tacrolimus with MMF or MP was also used for GVHD prophylaxis. All patients engrafted at a median of 16 and 18 days for neutrophil and thrombocyte recovery, respectively. Grades II–III acute GVHD developed in seven patients, and mild chronic GVHD was found in two patients. Two patients died within the first 100 days due to sepsis (TRM 12.5%). Eleven patients are currently alive, with a median follow‐up of 12 months (range 6–22 months). The 12‐month OS and DFS were 75 ± 10.8% and 68.8 ± 11.6%, respectively. Our results with these high‐risk patients are encouraging for haploidentical HSCT in pediatric patients. Future studies should continue to assess haploidentical HSCT, including comparison of other modalities, in a primary pediatric population.     

Temporary resolution of insulin requirement in acquired partial lipodystrophy associated with chronic graft‐versus‐host disease

This is a case presentation describing a high insulin requirement that suddenly resolved in a patient with acute lymphoblastic leukemia treated with stem cell transplantation complicated by chronic graft‐versus‐host disease. The patient was diagnosed with acquired partial lipodystrophy that did not require alternative therapies such as leptin or insulin‐like growth factor 1.     

High‐dose chemotherapy with autologous stem cell rescue for treatment of retinoblastoma: Report of five cases

RB is a primarily pediatric cancer arising from the retina, initiated by biallelic loss of the RB1 gene. We report five children with bilateral RB (n = 3), extra‐ocular disseminated RB, or disseminated relapsed RB, who were treated with tandem high‐dose chemotherapy and autologous stem cell rescue. All patients received at least 2.2 × 10⁶/kg CD34⁺ (median, 3.9 × 10⁶/kg) cells. The preparative regimen for course 1 was carboplatin, thiotepa, etoposide, and for course 2, CM and melphalan. ANC of at least 0.5 × 10⁹/L occurred at a median of 11 days (range, 10–12) and 15 days (range, 12–16) after the first and second procedure, respectively. Platelet engraftment occurred at a median of 13 days (range, 12–17) and 15 days (range, 14–22) after the first and second procedure, respectively. All of the five patients treated remain alive and disease free at the last follow‐up time, ranging between 21 and 44 months after completion of autologous transplant. Additional therapy was required in one patient, in whom enucleation had to be performed because of early disease relapse, refractory to local therapy. Intensification of chemotherapy with repeated high‐dose chemotherapy and autologous rescue appears an acceptable choice in selected cases with bilateral or extra‐ocular disease, either recurrent or refractory.     

Successful treatment of post‐transplant CMV meningoencephalitis with third‐party CMV virus‐specific T cells: Lessons learned

Cytomegalovirus encephalitis is a challenging life‐threatening complication following hematopoietic stem cell transplantation for which medical treatment is usually ineffective or toxic. However, in recent years, adoptive T‐cell therapy has been reported to provide a significant chance of cure for patients with viral infections. Herein, two cases of pediatric patients successfully treated with third‐party donor‐derived virus‐specific T cells for CMV meningoencephalitis are reported.     

Successful unrelated umbilical cord blood transplantation for class 3 β‐thalassemia major using a reduced‐toxicity regimen

Unrelated umbilical CB transplant for class 3 β‐thalassemia major is associated with an increased risk of mortality and non‐engraftment. We describe two patients who underwent successful unrelated umbilical CB transplant using a novel reduced‐toxicity preparative regimen. This regimen may be sufficiently immunosuppressive and myeloablative to ensure engraftment with reduced risks of toxicity and mortality. Close monitoring of HHV‐6 viral load is advised for patients undergoing transplant with this regimen.     

Human herpesvirus‐6 viremia is not associated with poor clinical outcomes in children following allogeneic hematopoietic cell transplantation

HHV‐6 is an evolving pathogen in the field of AlloHCT. However, the impact of HHV‐6 on AlloHCT outcomes remains to be elucidated. We studied the incidence and clinical impact of HHV‐6 viremia in children following AlloHCT. One hundred consecutive children were monitored weekly by plasma PCR for the first 180 days following AlloHCT for HHV‐6, CMV, EBV, and ADV. HHV‐6 viremia was defined as plasma PCR >1000 viral copies/mL. The median age was nine yr. Following AlloHCT, 19% (95% CI 11.3–26.7%) of patients had HHV‐6 viremia, with the highest incidence of reactivation (14/19, 73%) occurring during day +15‐day +98. The proportion of platelet engraftment by day +180 was lower in patients with HHV‐6 viremia (58%) than in those without HHV‐6 viremia (82%), p = 0.028. Delay in neutrophil and platelet engraftment was not associated with HHV‐6 viremia in multivariate analysis. Similarly, HHV‐6 viremia was not associated with TRM in multivariate analysis (p = 0.15). In summary, HHV‐6 viremia is prevalent in pediatric AlloHCT recipients. Based on our study results, we recommend that HHV‐6 PCR should only be performed on clinical suspicion.     

Transplant‐related mortality and survival in children with malignancies treated with allogeneic hematopoietic stem cell transplantation. A multicenter analysis

The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant‐related reasons. The most frequently observed causes of TRM were toxic complications effecting with organ failure (38%), followed by infections (26%), PTLD (14.3%), and GvHD (16.7%). There was no statistical difference in the incidence of TRM depending on stem cell source (P = .209) and primary diagnosis (P = .301). According to TRM score, TRM was significantly higher in high‐risk group (P = .006). High‐risk patients had lower survival comparing to low/intermediate group (P = .0001). OS did not differ between ALL, AML, and MDS/JMML groups. The study confirmed the utility of factors included in TRM score stratification in assessing the risk of transplant procedure in pediatric patients transplanted for malignancies.     

Phase‐1 study of siplizumab in the treatment of pediatric patients with at least grade II newly diagnosed acute graft‐versus‐host disease

Brochstein JA, Grupp S, Yang H, Pillemer SR, Geba GP. Phase‐1 study of siplizumab in the treatment of pediatric patients with at least grade II newly diagnosed acute graft‐versus‐host disease.
Pediatr Transplantation 2010:14:233–241. © 2009 John Wiley & Sons A/S. Abstract: In a phase‐1 study, siplizumab, a humanized anti‐CD2 monoclonal antibody, was administered (0.012 or 0.04 mg/kg) to 10 pediatric patients with ≥ grade‐II newly diagnosed, non‐steroid‐refractory aGvHD after BMT or PBSCT. SAEs and other AEs including infections, and GvHD staging changes (overall, skin, liver, gut) were evaluated over 364 days. Patients reported a total of 121 AEs (19 grade‐3, 5 grade‐4 0.012 mg/kg group; 17 grade‐3, 17 grade‐4 0.04 mg/kg group) and 14 SAEs (five grade‐3, three grade‐4, 0.012 mg/kg group; three grade‐3, 0.04 mg/kg group); 15 AEs in five patients and four SAEs in three patients (fever, PTLD, adenoviral infection, and EBV lymphoma) were considered siplizumab‐related. Six deaths occurred (study days 17–267); two were considered siplizumab‐related: one from EBV‐associated PTLD (0.012 mg/kg) and one from adenoviral infection (0.04 mg/kg); the other four deaths could potentially be attributed in part to study drug Three patients (one, 0.012 mg/kg group; two, 0.04 mg/kg group) developed PTLD. By study day 12, GvHD grade decreased in 3/5 and 2/5 patients in the 0.012 and 0.04 mg/kg groups, respectively; remission (grade 0) occurred in one patient in each group. Four of five patients (0.012 mg/kg group) and one of four patients (0.04 mg/kg group) achieved grade 0 GvHD during the first 100 study days (55.6% response). While treatment with siplizumab was associated with improvement of GvHD and remission in some pediatric patients, the overall high morbidity, mortality, and occurrence of PTLD is of safety concern, not warranting further development of siplizumab for the treatment of aGvHD in children.     

Non‐sibling hematopoietic stem cell transplantation using myeloablative conditioning regimen in children with Maroteaux‐Lamy syndrome: A brief report

Maroteaux‐Lamy syndrome is a rare inherited lysosomal storage disorder with a progressive course. HSCT is a curable option for treatment in these patients. The following report describes our experience in HSCT for three patients with Maroteaux‐Lamy syndrome using non‐sibling donors. All of the patients received the same myeloablative regimen consisting of intravenous busulfan, cyclophosphamide, and rabbit antithymocyte globulin. Patients underwent HSCT from haploidentical other‐related (n=1), full‐matched other‐related (n=1), and one‐locus‐mismatched unrelated donor. Stem cell sources included bone marrow (n=1), peripheral blood (n=1), and cord blood (n=1). Currently, two patients who received transplant from other‐related donors showed full engraftment and regression of the symptoms of the disease, while for the patient with unrelated cord blood donor, graft failure resulted in progression of the disease and death. The result of our study showed beneficial effects of HSCT even from heterozygote donor. Due to rarity of the disease, future multicenter studies are recommended to find the best treatment approaches based on the patients’ status.     

Homozygous α‐thalassemia: Challenges surrounding early identification,treatment, and cure

The prognosis for homozygous α‐thalassemia is changing. Prenatal diagnosis and intrauterine transfusions (IUT) reduce maternofetal morbidity and mortality; hematopoietic stem cell transplant (HSCT) is curative. Empiric evidence to support IUT and HSCT to treat homozygous α‐thalassemia is lacking. The first case of curative HSCT for homozygous α‐thalassemia was reported in 1997. Nearly 20 years later, five additional reports are published. We review the literature and report an institutional experience with three homozygous α‐thalassemia patients. The first died shortly after birth. The second underwent HSCT after years of chronic transfusion therapy. The third benefited from IUT and HSCT. These cases exemplify the varied outcomes associated with this condition.     

Hepatosplenic γδ T‐cell lymphoma of two adolescents: Case report and retrospective literature review in children,adolescents, and young adults

HSTCL is a highly aggressive malignancy with a poor prognosis. Case series and accounts have reported the use of different chemotherapy regimens with diverse patient outcomes. Most long‐term survivors had undergone high‐dose chemotherapy with autologous or allogeneic HCT. We describe two pediatric patients with HSTCL who were treated with chemotherapy followed by allogeneic HCT. Both patients are alive and in complete remission 2 and 8 years after therapy. Multiagent chemotherapy followed with allogeneic HCT seems to provide patients who have chemotherapy‐sensitive disease a long‐term disease‐free survival.     

Reduced‐toxicity alternate‐donor stem cell transplantation with posttransplant cyclophosphamide for primary immunodeficiency disorders

We describe here the outcomes of reduced‐toxicity alternate‐donor stem cell transplant (SCT) with posttransplant cyclophosphamide (PTCy) for primary immunodeficiency disorders (PIDs) in eight children (haploidentical—seven and matched unrelated donor—one). The conditioning was with serotherapy (alemtuzumab‐3/rabbit‐anti‐thymoglobulin‐5); fludarabine, cyclophosphamide, and total body irradiation‐5 (additional thiotepa‐3); fludarabine and treosulfan‐2; and fludarabine and busulfan‐1. All received PTCy 50 mg/kg on days 3 and 4 as graft versus host disease prophylaxis along with tacrolimus and mycophenolate. Mean CD34 dose was 13.8 × 10⁶/kg. Two children died because of PIDs. Acute graft versus host disease up to grades I and II was seen in three children. All six survivors are fully donor and disease free at median follow‐up of 753 days. Alternate donor SCT with PTCy is feasible in PID and has good outcomes.