Diagnosis and treatment of passenger lymphocyte syndrome following secondary ABO-incompatible allogeneic hematopoietic stem cell transplantation / 中国输血杂志

【Objective】 To investigate the clinical characteristics and diagnosis and treatment of passenger lymphocyte syndrome (PLS) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). 【Methods】 A total of 489 patients who underwent allo-HSCT in Suzhou Hongci Hematology Hospital were retrospectively enrolled. The clinical process, diagnosis and treatment measures and prognosis of four patients complicated with PLS after transplantation were analyzed. 【Results】 Among the 489 patients, 4 were diagnosed with PLS. The blood types of donor/recipient ABO were all secondary incompatible (The blood type of donors were O and the recipients were A or B). The overall incidence of PLS in allo-HSCT was 0.82%(4/489)and 2.2%(4/179)in transplants with donor/recipient secondary incompatible ABO-blood types. PLS occured in 6-13 days after donor stem cell infusion. Clinical manifestations were dizziness and fatigue, low back pain, jaundice, deepening urine, rapid decrease in hemoglobin on laboratory tests, elevated indirect bilirubin and lactate dehydrogenase, positive urobilinogen, positive direct anti-human globulin test (DAT), and anti-A or anti-B antibodies against recipient red blood cells were detected in plasma. After the treatment of O-type washed red blood cells, methylprednisolone, gamma globulin, rituximab and other treatments, the hemolysis was improved. All patients achieved engraftment of neutrophil and platelet. Red blood cell transfusion was halted in 3 weeks. 【Conclusion】 PLS is a rare complication of allo-HSCT, which mainly occurs in allo-HSCT patients with secondary incompatibility of ABO blood group of donor/recipient. The clinical prognosis is good after properly treatment.

Expert consensus on recipient blood type test and blood component transfusion after ABO-incompatibility hematopoietic stem cell transplantation / 中国输血杂志

At present, ABO-incompatibility hematopoietic stem cell transplantation (ABOi-HSCT) accounts for 30%~50% of the total HSCT, and is no longer a major obstacle to HSCT. Transfusion therapy is an important treatment for HSCT patients during transplantation, and correct blood typing and blood selection of blood component are particularly important.For patients with ABOi-HSCT, one of the challenging issues for laboratory technician is to complete ABO blood group testing and report before, during, and after ABOi-HSCT, as well as the selection of blood components that balance transfusion safety and efficacy. This consensus was jointly discussed by domestic experts in transfusion medicine and hematology in China, and 7 recommended opinions were extracted to further standardize the blood typing and blood component infusion strategies for ABOi-HSCT patients, provide technical support for standardized blood typing reports and accurate blood component infusion for HSCT patients, and continuously improve the safety and efficacy of blood transfusion.

Research progress in hematopoietic stem cell transplantation for bone marrow acute radiation syndrome / 中国辐射卫生

As is known, the nuclear accident resulting from the explosion of a nuclear weapon or the release of nuclear material could cause acute radiation syndrome within a short time. The study had found that the dose of > 0.7 Gy radiation on human body can result in persistent myelosuppression, a kind of acute radiation syndrome, leading to pancytopenia, bleeding, infection and other injuries. Several evidences also have shown that hematopoietic stem cell is conducive to repair hematopoietic injury in bone marrow, improve hematopoietic microenvironment and promote hematopoietic reconstruction. Therefore, hematopoietic stem cell transplantation is widely considered as the main treatment of the bone marrow acute radiation syndrome. However, before a surgery of hematopoietic stem cell transplantation, it still needs more research on donor selection, formulation of preconditioning and prevention of complications such as graft-versus-host disease. This paper mainly summarizes the application and research progress of hematopoietic stem cell transplantation in treating radiation injury.

Autosomal dominant osteopetrosis type II

Osteopetrosis ("marble bone disease") is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs. The overall incidence of these conditions is difficult to estimate but autosomal recessive osteopetrosis (ARO) has an incidence of 1 in 250,000 births, and autosomal dominant osteopetrosis (ADO) has an incidence of 1 in 20,000 births. Osteopetrotic conditions vary greatly in their presentation and severity, ranging from neonatal onset with life-threatening complications such as bone marrow failure (e.g. classic or "malignant" ARO), to the incidental finding of osteopetrosis on radiographs (e.g. osteopoikilosis). Classic ARO is characterised by fractures, short stature, compressive neuropathies, hypocalcaemia with attendant tetanic seizures, and life-threatening pancytopaenia. The presence of primary neurodegeneration, mental retardation, skin and immune system involvement, or renal tubular acidosis may point to rarer osteopetrosis variants, whereas onset of primarily skeletal manifestations such as fractures and osteomyelitis in late childhood or adolescence is typical of ADO. Osteopetrosis is caused by failure of osteoclast development or function and mutations in at least 10 genes have been identified as causative in humans, accounting for 70% of all cases. These conditions can be inherited as autosomal recessive, dominant or X linked traits with the most severe forms being autosomal recessive. Diagnosis is largely based on clinical and radiographic evaluation, confirmed by gene testing where applicable, and paves the way to understanding natural history, specific treatment where available, counselling regarding recurrence risks, and prenatal diagnosis in severe forms. Treatment of osteopetrotic conditions is largely symptomatic, although haematopoietic stem cell transplantation is employed for the most severe forms associated with bone marrow failure and currently offers the best chance of longer term survival in this group. The severe infantile forms of osteopetrosis are associated with diminished life expectancy, with most untreated children dying in the first decade as a complication of bone marrow suppression. Life expectancy in the adult onset forms is normal.

Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation / 医学前沿

Bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation (HSCT) is a major cause of morbidity and mortality with limited treatment options. Lung transplantation (LTX) has been rarely reported as a treatment option for selected HSCT recipients with this problem. In the present study, we reported six patients who underwent LTX due to BOS after HSCT (two females, four males) from January 2012 to December 2014 in our center. The median time from HSCT to diagnosis of BOS was 2.5 years (ranging from 1 to 5 years). At a median time of 4 years (ranging from 2 to 5 years) after diagnosis of BOS, four patients received bilateral sequential LTX, and two patients received single LTX. One of the recipients suffered from mild acute rejection after LTX, another suffered from primary lung graft dysfunction on post-operation day 2, and three experienced fungal infections. The median time for follow-up after LTX was 19.5 months (ranging from 12 to 39 months). At present, all patients are alive with good functional capacity and no relapse of BOS and hematologic malignancy conditions. Patients who received bilateral LTX have better pulmonary functions than patients who received single LTX.

Evaluación de interacción medicamentosa de voriconazol-ciclosporina en pacientes pediátricos que reciben trasplante de precursores hematopoyéticos (2013-2014) / Drug interaction of voriconazole-cyclosporine in children undergoing hematopoietic stem cell transplantation (2013-2014)

Background: Drug interactions (DI) in patients receiving hematopoietic stem cell transplantation (HSCT) are common and clinically significant, highlighting: anticonvulsants, voriconazole (VCZ) and cyclosporine (CsA), which require monitoring. Objective: To describe the interactions between CsA-VCZ in children undergoing HSCT. Methods: Retrospective, descriptive study in immunocompromised children hospitalized since January 2013 to December 2014 at Bone Marrow Transplant Unit, Hospital Dr. Luis Calvo Mackenna, who received CsA and VCZ. Results: The median age was 5 years (3-6) and the median weight was 20 kg (17-30). Sixtythree baseline drug levels were analyzed, of those, 27 were CsA drug levels obtained previous to using VCZ and 36 were CsA drug levels collected concomitantly with VCZ. In the group CsA previous to VCZ, the CsA dose was 4.6 ± 2.6 (mg/ kg/ day) and the CsA average level was 188.8 ± 84.1 (μg/ml). In the group of CsA concomitantly with VCZ, the dose of CsA was 5.5 ± 3.0 (mg/ kg/day) (p = 0.07) and CsA average level was significantly higher: 232.5 ± 106.7 (μg/ml) (p = 0.04). Conclusion: This study shows an increased level of CsA when it is used together with VCZ. Therapeutic drug monitoring could improve the management of the DI and optimize the co-administration of CsA and VCZ.

Introducción: Las interacciones medicamentosas (IM) en el trasplante de progenitores hematopoyéticos (TPH) son comunes y clínicamente significativas, especialmente en: anticonvulsivantes, voriconazol (VCZ) y ciclosporina (CsA). Objetivo: Describir las interacciones de CsA-VCZ en pacientes con TPH. Métodos: Estudio descriptivo, retrospectivo, en pacientes receptores de TPH entre enero de 2013 y diciembre de 2014 en la Unidad de Trasplante de Médula Ósea del Hospital Dr. Luis Calvo Mackenna, que recibieran CsA y VCZ. Resultados: Edad media: 5 años (3-6), peso promedio: 20 kg (17-30). Se analizaron 63 concentraciones plasmáticas de CsA, 27 eran concentraciones de CsA previas al uso de VCZ y 36 concentraciones plasmáticas de CsA concomitantes con VCZ. En el grupo de CsA previo a VCZ, la dosis de CsA fue 4,6 ± 2,6 (mg/kg/día) y la concentración media de CsA 188,8 ± 84,1 (μg/ml). En el grupo de CsA en forma concomitante con VCZ, la dosis de CsA fue de 5,5 ± 3,0 (mg/kg/día) (p 0,07) y la concentración media de CsA fue: 232,5 ± 106,7 (μg/ml) (p = 0,04). Conclusión: Se demostró un aumento de las concentraciones plasmáticas de CsA en IM con VCZ. La monitorización terapéutica podría mejorar el manejo de la IM y optimizar la coadministración de CsA y VCZ.

Clinical Manifestations and Risk Factors of Ocular Graft-versus-Host Disease (GVHD) after Hematopoietic Stem Cell Transplantation

PURPOSE: To investigate the incidence, clinical manifestations, and risk factors of ocular graft-versus-host disease (GVHD) as well as the survival of the patients after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: The medical records of 99 patients who visited our clinic and were screened for ocular GVHD after allogeneic HSCT were reviewed retrospectively. Subjects were divided into 2 groups depending on the occurrence of ocular GVHD on slit-lamp biomicroscopy. We compared clinical manifestations and survival between the 2 groups and analyzed the risk factors associated with the development of ocular GVHD. RESULTS: Ocular GVHD was diagnosed in 38 patients (38.38%) at a mean of 315 days after HSCT. Out of the 38 patients who developed ocular GVHD, 22 patients (57.89%) were diagnosed with dry eye only and 16 patients (42.11%) were diagnosed with conjunctival disease. The presence of extraocular GVHD (hazard ratio (HR) 35.76, p < 0.001), the number of extraocular GVHD (HR 3.07, p < 0.001), skin GVHD (HR 2.31, p = 0.029), oral GVHD (HR 8.16, p < 0.001), and gastrointestinal tract GVHD (HR 5.00, p = 0.002) were independent risk factors of ocular GVHD. Comparisons of the survival demonstrated decreased survival of patients with conjunctival disease compared to patients without ocular GVHD and patients with dry eye only, but there was no statistically significant differences (log rank test, p = 0.208). CONCLUSIONS: Ocular GVHD is common after allogeneic HSCT. The majority of ocular GVHD occurs in the chronic stage and is associated with decreased survival. Therefore, more intensive and long-term follow-up with ophthalmic and systemic monitoring is necessary, especially in patients who have extraocular GVHD, for early recognition and proper treatment of ocular GVHD.

A Case of Autoimmune Hemolytic Anemia Complicating Hematopoietic Cell Transplantation / 대한진단검사의학회지

A 32-yr-old male diagnosed with myelodysplastic syndrome underwent an unmanipulated, unrelated, HLA matched, peripheral blood stem cell transplantation. The patient and donor were both blood type O, CcDEe. Twelve weeks post-transplantation, he developed acute autoimmune hemolytic anemia (AIHA). He was transfused multiple times with washed O red cells. High-dose steroid therapy was initiated and he underwent splenectomy; however, AIHA was refractory to therapy. The patient was further treated with combined treatment modalities including immunosuppressive therapy with mycophenolate mofetil and cyclosporine and three cycles of plasma exchange, and AIHA responded to treatment. This is the third case of AIHA complicating hematopoietic stem cell transplantation reported in Korea. Since AIHA is relatively common after hematopoietic stem cell transplantation, accurate and timely diagnosis of the disease and treatment strategies with multiple modalities are necessary.

Short-term Results of Hematopoietic Stem Cell Transplantation for Children with Myelodysplastic Syndrome

PURPOSE: In most cases, myelodysplastic syndrome(MDS) transforms into a more aggressive state or acute myelogenous leukemia; it's prognosis is very poor. It is believed that hematopoietic stem cell transplantation(HSCT) is the only curative treatment of MDS, but available data in children are very sparse. In this report, the short term outcome of HSCT in childhood MDS was analyzed. METHODS: Ten children with MDS(CMMoL 5, RAEB 3, RAEBt 2) underwent HSCT(HLA- matched sibling transplantation 4, HLA-matched unrelated transplantation 4, cord blood transplantation 1, HLA-mismatched familial transplantation 1) between November 1995 and January 2001 at St. Mary's Hospital. Median follow-up duration was 11 months. RESULTS: Engraftment was successful in all cases and 8 patients are alive without disease. Three cases of VOD were observed and improved without complication. Four cases of grade II and 1 case of grade III acute GVHD were observed and well controlled with treatment. Three patients relapsed after transplantation. One patient is alive without disease after cytoreduction with allogenic stem cell rescue and 2 patients died of relapse. CONCLUSION: HSCT is a curative strategy of MDS and the survival rate is relatively higher than that of adults. But there is an obvious need for more studies because of the small number of patients and the short duration of the follow-up.