Follicular mucinosis occurring after bone marrow transplantation in a patient with acute lymphoblastic leukemia.

Follicular mucinosis (FM) is characterized histologically by mucinous degeneration of the outer root sheath of the hair follicle and sebaceous gland, accompanied by inflammatory infiltrate. It can occur as a primary idiopathic disorder or in association with benign or malignant diseases, most notably mycosis fungoides. In addition, it also can be found incidentally on histology. We describe an unusual case of follicular mucinosis in a 19-year-old man with acute lymphoblastic leukemia (ALL). One month after bone marrow transplantation, he developed cutaneous graft-versus-host disease (GVHD) involving the palms and soles, which was followed 12 days later by the appearance of multiple erythematous follicular papules and plaques on his face, auricles, and postauricular area. Biopsy of follicular plaque revealed changes of follicular mucinosis without evidence of graft-versus-host disease or leukemia cutis. The follicular rash was associated with prominent peripheral eosinophilia. The rash and eosinophilia resolved after 2 and 4 weeks, respectively. In conclusion, we report a case of FM occurring as a transient reaction during the course of cutaneous GVHD following bone marrow transplantation for ALL. Awareness of this condition may avoid undue concern that the rash might represent a manifestation of GVHD, cutaneous relapse of the hematological malignancy, or a drug allergy.     

Cyclosporine-induced encephalopathy in a patient with relapsed acute myeloid leukemia treated with unrelated allogeneic bone marrow transplantation.

Cyclosporine (CSP) is the most frequently used immunosuppressive agent for prevention of graft versus host disease (GVHD) in allogeneic bone marrow transplantation (BMT). Some adverse effects such as hepatic and renal toxicity have been frequently encountered, but central nervous system (CNS) toxicity caused by CSP is rare. We report an adult male patient with acute myeloid leukemia who developed CSP-induced encephalopathy under treatment for allogeneic BMT from an unrelated donor. Methotrexate and CSP were used for GVHD prophylaxis. Leukocyte and platelet engraftment were successfully achieved on days 21 and 24 after BMT, respectively. Abrupt onset of mental confusion and disorientation occurred on day 25, followed by a generalized tonic clonic seizure and consciousness disturbance. The whole blood CSP level was 160.65 ng/mL. Magnetic resonance (MR) imaging revealed high signal intensities in the bilateral occipital lobes with predominant involvement of the cortical areas. The patient recovered from the CNS toxicity, but with slight memory impairment, 6 days after CSP was discontinued. When patients receiving CSP treatment for allogeneic BMT develop mental confusion, consciousness disturbance, or seizure, CSP-induced CNS toxicity should be taken into consideration.     

Daxx蛋白在儿童急性白血病骨髓细胞中的表达意义

目的探究Daxx蛋白在儿童急性白血病骨髓细胞中的表达意义。方法2010年2月至2014年10月汕头大学医学院第一附属医院儿科收治住院的急性白血病患儿100例为观察组,又根据疾病类型分为3个亚组,即急性淋巴细胞白血病(ALL)组49例,急性非淋巴细胞白血病(ANLL)组21例,急性髓细胞白血病(AML)组30例。对照组30例,为同年龄正常健康儿童。采用免疫组织化学方法检测Daxx蛋白的表达。结果对照组儿童骨髓细胞中Daxx蛋白的表达阳性率与ALL组比较差异无统计学意义(P0.008 3);对照组儿童骨髓细胞中Daxx蛋白的表达阳性率显著低于ANLL组和AML组,差异有统计学意义(P0.008 3)。对照组中Daxx蛋白在儿童急性白血病骨髓中的表达(6.01±1.13)μg/L,显著高于ALL组(3.55±2.32)μg/L、ANLL组(3.54±2.47)μg/L、AML组(3.12±1.56)μg/L,差异有统计学意义(P0.05)。结论 Daxx蛋白在儿童急性白血病骨髓细胞中过度表达,可能对促进白血病细胞的增殖、生长过程起到重要作用。     

Acute respiratory distress syndrome due to tuberculosis in a child after allogeneic bone marrow transplantation for acute lymphoblastic leukemia.

We report the occurrence of tuberculosis in a 10-year-old Taiwanese boy, approximately 4 months after he received a matched-related bone marrow transplantation from his sister for acute T-cell lymphoblastic leukemia. After transplantation, grade III acute graft-versus-host disease developed and the patient was treated with prednisolone and cyclosporine. Marrow failure was noted on day 77 post-transplantation, however, after an episode of herpes zoster infection. Interstitial pneumonia, diagnosed on the basis of chest x-ray and computed tomography findings, occurred on day 120. Histologic examination of an open-lung biopsy specimen showed caseating granulomas and a few acid-fast bacilli. The patient died of acute respiratory distress syndrome, despite immediate implementation of antituberculosis therapy. Sputum cultures grew Mycobacterium tuberculosis 5 weeks later. This report demonstrates that the possibility of tuberculosis needs to be considered in immunocompromised patients, and that appropriate prophylaxis should be instituted in areas where tuberculosis is endemic.     

Congenital bone marrow failure syndromes associated with protean developmental defects and leukemia

Congenital bone marrow failure syndromes are associated with a number of congenital abnormalities affecting a wide range of organ systems. The underlying molecular abnormalities that cause these disorders affect normal embryonic development during the critical organogenesis phase (weeks 4 to 8). These syndromes predispose patients to leukemia and other malignancies, and these genetic disorders may represent the first hit of at least two hits necessary for malignant transformation. The molecular defects underlying these diseases are just beginning to be understood; mechanisms suggested by recent research include DNA repair (FA-A, FA-G); abnormalities of the ribosomes (DBA, DC); to disorders of electron transport (FA-C, Pearson's syndrome, Barth's syndrome). Understanding these molecular mechanisms provides the knowledge necessary to develop better therapy, possibly including gene therapy, offering for the first time the potential for curing the hematologic manifestations of these illnesses.     

自体骨髓移植联合大剂量化疗在妇科恶性肿瘤治疗中的应用

对５例手术难以切除的晚期妇科恶性肿瘤在手术前进行自体骨髓移植辅佐大剂量化疗。结果表明，自身骨髓移植为安全使用大剂量化疗提供了条件，而大剂量化疗则可为手术彻底切除肿瘤创造条件；４℃冷藏保存骨髓５天，仍可有效地用于自身骨髓移植。     

CA 125 levels in patients with ovarian carcinoma undergoing autologous bone marrow transplantation

Levels of CA 125, determined in three patients with ovarian carcinoma undergoing autologous bone marrow transplantation, dropped significantly in the month after bone marrow transplantation. This decrease was linear by multiple regression analysis. The CA 125 decrease after bone marrow transplantation in patients with nonevaluable or stable disease may represent biologic response to high-dose therapy.     

Pregnancy outcome in five women after autologous bone marrow transplantation for acute lymphoblastic leukaemia

There are reports of successful pregnancies in women with haematological malignancies after either autologous or allogeneic bone marrow transplantation (BMT). We report six cases of uncomplicated pregnancies in five women treated with high-dose chemotherapy, radiotherapy and autologous bone marrow transplantation (ABMT) for acute lymphoblastic leukaemia. One patient was diagnosed as having leukaemia during pregnancy. The pregnancy ended with medical termination. Each woman received conditioning regimens without total body irradiation (TBI). Of five women, who received AMBT, all resumed spontaneous cyclical menstruation post transplantation. All of them conceived naturally between 15-52 months following ABMT. We noted one miscarriage in our 29-year-old patient. Six pregnancies went to term and each resulted in the successful delivery of a full-term baby. We did not notice any case of relapse of leukaemia in pregnancy.     

Experimental transplantation study for possible transformation of bone marrow cells in the mouse placenta

The aim of the present study is to establish a mouse model of the transplantation of bone marrow cells into the placenta in mid-gestation. The mononuclear fraction of bone marrow cells was isolated by Ficoll gradient centrifugation from the femur bones of C57BL/6 green fluorescent protein (GFP) gene transgenic (Tg) mice. After intraperitoneal injection of pentobarbital sodium, the abdominal cavities of pregnant non-Tg (C57BL/6 or ICR) mice were opened at 9.5 days postcoitum (dpc). The mononuclear fraction of bone marrow cells from Tg mice (3-5 x 10(5)cells/3 microl) was directly injected into the placental portion of the pregnant uterus, at a depth of approximately 3 mm, using a 31-gauge injector. The placenta was sampled at 14.5 dpc. Confocal laser scanning microscopic analysis of the serial sections of the sampled placenta (150-250 sections/placenta) was carried out to detect GFP-positive cells and to assess immunostaining for cytokeratin, CD34, p57(Kip2) and prolactin. Most pregnant mice survived until sampling of the placenta at 14.5-18.5 dpc (88.9% for C57BL6 and 100% for ICR). The survival rate of fetuses from mice in which the placenta was transplanted with GFP-positive bone marrow cells was approximately 50%. A small population (0.154%) of injected bone marrow cells was retained in the placental tissue. Immunohistochemically, cytokeratin, CD34 and p57(Kip2) were positively stained in 0.062%, 4.5% and 2.1% of GFP-positive cells, respectively, while prolactin was not positive in any of the cells examined. GFP-positive bone marrow cells were successfully transplanted to the murine placenta. Future investigations of the specific antigens in bone marrow cells retained in the placenta may enable a better understanding of the local regulation of placental development.     

In utero hematopoietic stem cell transplantation with haploidentical donor adult bone marrow in a canine model

OBJECTIVE: Chimerism can be achieved in a canine model of in utero bone marrow transplantation with > or =1 x 10(8) CD34(+) haploidentical donor cells per kilogram without graft-versus-host disease. STUDY DESIGN: In utero bone marrow transplantation was performed by ultrasound-guided intraperitoneal infusion in 30- to 41-day-old canines with CD34(+) selected cells from paternal bone marrow at doses of 1.3 x 10(8) to 2.5 x 10(10) CD34(+) cells/kg. A method for marking control littermates was developed with intraperitoneal ethiodol. Postnatal studies included histologic, fluorescent in situ hybridization canine Y probe, and polymerase chain reaction-based chimerism analyses. RESULTS: Term survival was 86% to 100% for transplantations > or =34 days versus 14% and 43% at 30 and 31 days. Microchimerism (<1%) was demonstrated in tissues from 4 informative litters that included thymus, liver, skin, spleen, and intestine. Neither gestational age nor donor CD34 cell dosage altered the level of engraftment in these experiments. There was no evidence of graft-versus-host disease. CONCLUSION: In utero bone marrow transplantation in a canine model achieves microchimerism with high CD34(+) cell doses.     

New approaches in bone marrow transplantation: the utilization of hematopoietic stem cells

A detailed review of various methods of bone marrow transplantation is presented. Special emphasis is placed on the newest reports of fetal bone marrow transplantation in utero and stem cell reconstitution.     

Delayed erythropoiesis after major ABO-incompatible bone marrow transplantation: report of a case

Major ABO-incompatible bone marrow transplantation (BMT) may be associated with delayed erythropoiesis. A 38-year-old man (blood group O) with chronic myelogenous leukemia received a BMT from his histocompatibility antigen (HLA) identical brother (blood group A). The pre-BMT anti-A titer of the patient was 1:4. The harvested marrow was depleted of RBC by 6% hydroxyethyl starch sedimentation and Ficoll-Hypaque gradient centrifugation. No acute hemolysis occurred after marrow infusion. Myeloid and megakaryocytic series engrafted promptly. However, delayed erythropoiesis up to day 266 was found. Prolonged presence of anti-A antibody was noted for more than 250 days after BMT, although the peak titer was only 1:8. After the reconstitution of bone marrow, the erythroid series was confirmed as donor origin (RBC cell typing A). It is proposed that the prolonged presence of anti-A antibody probably produced from the residual host B lymphocytes, would destroy the regenerating erythroid precursors. Also, use of cyclosporin A may be associated with higher rates of prolonged production of anti-A/B antibodies and the subsequent delayed erythropoiesis.     

Percutaneous placement of femoral central venous catheter in patients undergoing transplantation of bone marrow

Five patients undergoing transplantation of autologous bone marrow underwent percutaneous placement of a double lumen central venous catheter into the inferior vena cava by way of the femoral vein. All had conditions that precluded access to the superior vena cava or other sites in the upper part of the torso. Patients ranged in age from 18 to 59 years. The double lumen central venous catheter was inserted using aseptic technique in the operating room, and the catheter exit site was dressed using sterile technique every 48 hours afterward. Patients received all irradiated blood product transfusions, intravenous fluids, intravenous antibiotics, parenteral alimentation and autologous bone marrow reinfusion through the catheter. The duration of severe neutropenia (less than 500 neutrophils per microliter) and severe thrombocytopenia (less than 20,000 platelets per microliter) ranged from zero to 24 days (median of 22 days) and five to 20 days (median of 15 days), respectively. Catheters remained in the groin area 23 to 45 days (median of 35 days). Complications included one catheter-related Streptococcus species infection and one Escherichi coli bacteremia. These infections resolved with the catheter in place after appropriate institution of antibiotics. No episodes of thrombosis, kinking, migration, extravasation of drugs or local infection were noted. Central venous catheters can be safely inserted and maintained in the groin area even in severely immunocompromised patients receiving bone marrow transplants.     

Matched unrelated donor bone marrow transplantation for the treatment of platinum refractory ovarian carcinoma: a case report

BACKGROUND: We are reporting on a case of platinum-refractory low-grade ovarian cancer responding to treatment with an allogeneic bone marrow transplantation from an unrelated donor. CASE: The 37-year-old patient received a preparative regimen consisting of fludarabine 25 mg/m(2) on days -6, -5, -4, -3 and -2, melphalan 70 mg/m(2) on days -3 and -2, and thymoglobulin 2 mg/kg on days -3, -2 and -1. An unrelated HLA-compatible bone marrow was infused on day 0. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. The patient demonstrated complete donor chimerism. Serial CT scans of the abdomen and pelvis over the following 15 months showed a slow regression of the malignant lesion. CONCLUSION: Engraftment of an unrelated donor marrow was achieved in a patient with ovarian cancer and induced a tumor response. This suggests the presence of a graft-versus-tumor effect in ovarian cancer. Further study is underway.     

Response to influenza vaccine in children with leukemia undergoing chemotherapy.

BACKGROUND AND PURPOSE: To assess the ability of children with acute lymphoblastic leukemia (ALL) to develop an antibody response after influenza vaccination. METHODS: A total of 65 children under 15 years old were studied, including 25 children with ALL undergoing chemotherapy, 30 with asthma in remission who were regularly followed at clinics, and 10 healthy children. The influenza vaccine contained antigens B/Yamanashi/166/98, A/New Caledonia/20/99 (H1N1), and A/Panama/2007/99 (H3N2). RESULTS: Children with ALL developed significant antibody titers to A/Panama /2007/ 99 antigen 4 weeks after the second immunization. Seroconversion rates after two doses of vaccine were 57.1 to 84.6% and seroresponse rates were between 24 and 60% in children with ALL. Compared to children with asthma in remission, who were regarded as immunocompetent individuals, the ALL children had less seroconversion and lower seroresponse rates to A/New Caledonia/20/99 (H1N1). The seroconversion and seroresponse rates to B/Yamanashi/166/98 and A/ Panama/2007/99(H3N2) antigens were comparable in asthmatic and leukemic children. On the other hand, the antibody response in children with ALL who received reinduction chemotherapy suggests that the therapy did not impair seroresponse rates. CONCLUSION: Our data suggest that the influenza vaccine is safe and effective in children with either ALL or asthma in Taiwan.     

Hematopoietic stem cell transplantation in Taiwanese children with primary immunodeficiency.

BACKGROUND AND PURPOSE: Since 1968 it has been known that hematopoietic stem cell transplantation (HSCT) can ameliorate primary immunodeficiencies, but data on the long-term efficacy of this treatment in Taiwan are limited. This study analyzed the outcome of HSCT and the immune reconstruction in 10 children with primary immunodeficiencies in Taiwan. METHODS: We retrospectively analyzed the outcome of HSCT in 10 children with primary immunodeficiencies between 1986 and 2002. The primary immunodeficiencies in these children included severe combined immunodeficiency (SCID) in 4, Wiskott-Aldrich syndrome (WAS) in 4, Chediak-Higashi syndrome (CHS) in 1, and leukocyte adhesion deficiency (LAD) in 1. The conditioning protocols included busulfan and cyclophosphamide in 2 patients with SCID, 3 patients with WAS, 1 patient with LAD and 1 patient with CHS. Anti-thymocyte globulin was given to only 1 patient with WAS and no conditioning therapy was given in 2 SCID patients. Graft-versus-host disease (GVHD) prophylaxis with cyclosporine (CsA) and methotrexate was prescribed in 6 children, CsA alone in 1, and CsA and T-cell depletion in 1. RESULTS: Six patients were cured and 1 improved during a follow-up period from 3.5 years to 13 years after transplantation. Three patients died of severe sepsis. Three patients developed acute GVHD, which was grade 2 in 2 patients, and grade 3 in 1. Veno-occlusive disease developed in 1 patient and chronic GVHD with contracture of joints in 1. CONCLUSIONS: Our results support the benefits of allo-HSCT in children with primary immunodeficiencies. However, HSCT should be performed as soon as possible before severe infection develops.     

Bone marrow transplantation from an HLA-matched unrelated donor for treatment of Chediak-Higashi syndrome.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by partial albinism and large granules in all granule-containing cells. It is also associated with recurrent pyogenic infections secondary to impaired leukocyte function. Most patients with CHS enter an accelerated phase that leads to repeated infections and bleeding complications, often resulting in death. The first accelerated phase may occur shortly after birth or several years later. There are no curative treatments, and bone marrow transplantation (BMT) is the treatment of choice. Here, we report the case of a boy with CHS. The diagnosis was made at the age of 1 month, on the basis of the characteristic clinical findings and family history. He received BMT from an HLA-matched unrelated donor. After BMT, fluorescent cytometric analysis of polymorphonuclear leukocytes showed normalized cellular granularity and a normal increase in CD11b expression on N-formylmethionyl-leucyl-phenylalanine stimulation. The accelerated phase did not develop during 27 months of follow-up. Without BMT, CHS is usually fatal before the age of 10 years. BMT from an unrelated donor may be an effective treatment option for those who lack sibling donors. In addition to the characteristic leukocytic dysfunctions, fluorescent cytometric analysis of cellular granularity and surface molecules offer useful diagnostic information.