상단 PDF Donor lymphocyte infusion after allogeneic stem cell transplantation in children

Donor lymphocyte infusion after allogeneic stem cell transplantation in children

Donor lymphocyte infusion after allogeneic stem cell transplantation in children

결론:저자들은 소아에서 al l oHSCT 후 DLI 는 GVHD와 골수 무형성이 조절 가 능할 정도라는 면에서 적용할 만한 치료법이라는 것을 알았으나 연소형 골수단 구성 백혈병을 제외한 급성백혈병의 이식술 후 재발에서의 효용성은 부족하여 새로운 전략이 필요할 것으로 생각된다. 핵심어:공여자 림프구 주입술,동종조혈모세포이식술,재발.[r]

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Clinical implications of chimerism after allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases

Clinical implications of chimerism after allogeneic hematopoietic stem cell transplantation in children with non-malignant diseases

a) Patient 88 achieved stable engraftment after the second HSCT, but died of transplant-related complications that resulted in multiple organ failure 5 months after the second HSCT. b) Although patient 127 received a second DLI, he did not achieve engraftment and died of transplant-related complications 81 days after HSCT. Abbreviations: PRCA, pure red cell anemia; SAA, severe aplastic anemia; KD, Kostmann disease; MRD, matched related donor; MMUD, mismatched unrelated donor; MMRD, mismatched related donor; Cy, cyclophosphamide; ATG, antithymocyte globulin; TBI, total body irradiation; Bu, busulfan; TCD, T-cell depletion; DLI, donor lymphocyte infusion; CR, complete remission; ND, not done.
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Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children

Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children

In addition, patients were divided into 2 groups: one with recovery of each lymphocyte subpopulation achieved at 3 months post-transplant and the other without recovery. Patient characteristics, conditions on transplant, complica- tions, and outcome parameters, such as relapse, event, and survival in the 2 groups were compared using chi-square or Fischer’s exact test. The probabilities of overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) at 2 years after HSCT for each group were estimated using Kaplan-Meyer method, where OS was defined as the time between date of HSCT and date of death/latest fol- low-up; RFS, the time between date of HSCT and date of diagnosis of relapse; and EFS, the time between date of HSCT and date of death, loss during follow-up, or diagnosis of relapse, whichever occurred first. Statistical differences were analyzed using Mann-Whitney’s rank-sum test.
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A case of donor-derived granulocytic sarcoma after allogeneic hematopoietic stem cell transplantation

A case of donor-derived granulocytic sarcoma after allogeneic hematopoietic stem cell transplantation

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. V O L U M E 4 5 ㆍ N U M B E R 1 ㆍ M A R C H 2 0 1 0 THE KOREAN JOURNAL OF HEMATOLOGY C A S E R E P O R T

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Early central nervous system complications after allogeneic hematopoietic stem cell transplantation in children

Early central nervous system complications after allogeneic hematopoietic stem cell transplantation in children

to CNS complications in allogeneic HSCT recipients, which confirms the observations made in other studies. Multivariate analysis showed that severe acute GHVD was an independent risk factor for the occurrence of CNS complications. In pa- tients undergoing allogeneic transplantation, the use of im- munosuppressive agents, such as CsA and tacrolimus, is an essential component in the control of GVHD. Patients who experience severe acute GVHD are predisposed to CNI-asso- ciated neurotoxicity because they are usually managed with aggressive immunosuppression therapy. In addition, cortico- steroids used during the treatment of GVHD may contribute to the development of neurological events [13]. Moreover, it has been reported that patients with severe GVHD tend to experience not only CNS complications associated with immunosuppressive drugs but also CNS infections or TMA-associated neurological events due to immunosu- ppression [1, 14].
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Wernicke’s encephalopathy following allogeneic hematopoietic stem cell transplantation

Wernicke’s encephalopathy following allogeneic hematopoietic stem cell transplantation

Donor cluster of differentiation (CD) 34 + cells (2.68×10 6 / kg) were collected after mobilization of peripheral blood stem cells with granulocyte-colony stimulating factor. After conditioning the patient with a classic busulfan and cyclo- phosphamide regimen, the prepared donor cells were infused into the patient without any acute complications. During the conditioning period, the patient developed grade 4 nausea and anorexia and could not receive oral nutrition. TPN was quickly applied for providing the much-needed nutritional support. The patient gradually recovered from neutropenia on day 12 of HSCT without any adverse events, and successful engraftment was confirmed by an engraftment assay per- formed on day 28 of HSCT. However, owing to continued loss of appetite and acute GVHD involving the gastro- intestinal tract, TPN was maintained for over a month.
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The impact of HLA matching on unrelated donor hematopoietic stem cell transplantation in Korean children

The impact of HLA matching on unrelated donor hematopoietic stem cell transplantation in Korean children

Relapse-related death was defined as death caused by relapse after HSCT, regardless of any further treatment for relapse. 4. Statistical analysis Continuous variables are expressed as median (range), whereas categorical variables are expressed as proportions and/or percentages. Descriptive statistical analysis was per- formed to compare patient baseline and post-transplantation characteristics. Two-sided Fisher’s exact test was used in 2×2 table analysis. OS curves were calculated using Kaplan- Meier method and compared using the log-rank test. Cumula- tive incidence curves for TRM and relapse with or without death were constructed to reflect the time to relapse and time to transplant-related death as competing risks. Cumulative incidences were compared using Gray’s test. Both analyses were performed using Cox regression for OS, TRM and re- lapse-related death, and logistic regression for aGVHD and engraftment. Variables considered included HLA match, pa- tient age, donor-recipient gender match, disease status, stem cell source, and intensity of conditioning. All reported P -val- ues are 2-sided, and P -value of <0.05 was considered statisti- cally significant. All statistical analyses were performed using SPSS Version 18.0 software program or R 2.10.1.
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BLOOD RESEARCH

SOCS1 and SOCS3 are expressed in mononuclear cells in human cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

Therefore, we further analyzed the expression levels of SOCS1 and SOCS3 between allogeneic HSCT recipients with CMV viremia and those without CMV viremia, according to the occurrence of aGVHD. SOCS1 gene expression was higher in the CMV+ group and the CMV+GVHD- subgroup than in the healthy donor group, whereas it was not increased in the CMV+GVHD+ subgroup. Blalock et al . showed up-reg- ulation of SOCS3 gene expression by STAT3 phosphorylation after murine CMV infection in T H 17 cells, suggesting that SOCS3 is expressed after CMV infection [27]. However, we still cannot exclude the possibility that the change in SOCS gene expressions in response to human CMV infection is cell-type–, species-type–, and acute or chronic-status–
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Lineage-specific chimerism analysis in nucleated cells, T cells and natural killer cells after myeloablative allogeneic hematopoietic stem cell transplantation

Lineage-specific chimerism analysis in nucleated cells, T cells and natural killer cells after myeloablative allogeneic hematopoietic stem cell transplantation

Abbreviations: UPN, unique patient number; CD34 + , positive selection of CD34 cells; DLI, donor leukocyte infusion; M, male; BM, bone marrow; MC, mixed chimerism; CC, complete chimerism; PBSC, peripheral blood stem cell; F, female; SAA, severe aplastic anemia; MDS, myelodysplastic syndrome; PNH, paroxysmal nocturnal hemoglobinuria. or without further manipulation of different cell subpo- pulations. It is important to realize that patients could show complete chimerism (CC) in one cell type, for example, T cells, whereas others could be totally or in part recipi- ent-derived. This is called split chimerism [3, 8].
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BLOOD RESEARCH

Favorable outcome of allogeneic hematopoietic stem cell transplantation followed by post-transplant treatment with imatinib in children with Philadelphia chromosome-positive acute lymphoblastic leukemia

All 12 patients achieved hematologic remission before HSCT, although one relapsed before HSCT and achieved a second hematologic remission following a second induction chemo- therapy regimen. Ten patients achieved cytogenetic re- mission, one still had the t(9:22) chromosome, and there were no chromosomal data before HSCT for one case. Seven patients achieved molecular remission, three patients did not, and there were no BCR-ABL molecular analysis data before HSCT for two patients. The type of HSCT donor varied: there was one matched sibling, one HLA-DR mis- matched sibling, and one haploidentical donor; the other nine donors were unrelated. Four of the nine unrelated do- nors were mismatched unrelated donors: two were 7/8 HLA matched donors, one was 6/8 HLA matched donor and the other one was 5/8 HLA matched donor. The graft sources were bone marrow in four patients, mobilized peripheral blood stem cell in five, and umbilical cord blood in three patients. All patients received fractionated total body irradi- ation of 6.0–14.0 Gy followed by cyclophosphamide at a dose of 50–60 mg/kg/day over two days and/or fludarabine
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Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

of acute GVHD might be used as a predictive factor to estimate its final severity. Although the role of B cells in the development of chronic GVHD is relatively well known, their role in the develop- ment of acute GVHD is still controversial. Furthermore, it is very difficult to evaluate the role of B cells from the donor or recipient in the development of acute GVHD, because the reconstitution of the B cell compartment required for humoral immunity may take up to 2 years after HSCT [13]. There is some evidence for adverse effects of donor B cells. High numbers of B cells in apheresis products correlated with an increased incidence of acute GVHD and increased treatment-related mortality [14]. Early-phase clinical trials indicate that B cell depletion with rituximab has beneficial effects on acute GVHD [3]. We showed that a higher serum concentration of B cell-activating factors such as BAFF or APRIL at diagnosis of acute GVHD might be associated with a higher grade of acute GVHD. Therefore, we concluded that B cells might play an important role in the development of acute GVHD, and BAFF/ALC or APRIL/ALC might be significant predictive factors for estimating the severity of the condition.
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BLOOD RESEARCH

Recent advances in haploidentical hematopoietic stem cell transplantation using ex vivo T cell-depleted graft in children and adolescents

Alternatively, allogeneic HSCT from haploidentical family members could provide donors for virtually all patients who need HSCT. Although the early attempts at allogeneic HSCT from haploidentical family donor (HFD) were disappointing, recent advances in the effec- tive ex vivo depletion of T cells or unmanipulated in vivo regulation of T cells, better suppor- tive care, and optimal conditioning regimens have significantly improved the outcomes of haploidentical HSCT. The ex vivo techniques used to remove T cells have evolved from the selection of CD34 + hematopoietic stem cell progenitors to the depletion of CD3 + cells, and more recently to the depletion of  + T cells. The recent emerging evidence for ex vivo T cell-depleted haploidentical HSCT has provided additional therapeutic op- tions for pediatric patients with diseases curable by HSCT but has not found a suitable related or unrelated donor. This review discusses recent advances in haploidentical HSCT, focusing on transplant using ex vivo T cell-depleted grafts. In addition, our experiences with this novel approach for the treatment of pediatric patients with malignant and non-malignant diseases are described.
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The effectiveness of tacrolimus and minidose methotrexate in the prevention of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in children: a single-center study in Korea

The effectiveness of tacrolimus and minidose methotrexate in the prevention of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in children: a single-center study in Korea

2. GVHD prophylaxis Tacrolimus was administered intravenously since the day before transplantation at 0.03 mg/kg/day via continuous infusion. Following engraftment, once the patient was able to consume oral medications, tacrolimus was administered as an oral dose at a concentration of 4 times the intravenous (IV) dose. The oral dose was administered in 2 doses every 12 h. Tacrolimus levels were monitored every second day, and the dosage was adjusted to maintain trough levels be- tween 5 and 15 ng/mL. In the absence of GVHD, tacrolimus dosage was subsequently tapered by 25% per month and discontinued by day 180. Children with aGVHD continued to receive tacrolimus at the discretion of the physician.
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Allogeneic stem cell transplantation for neuroblastoma Perspective

Allogeneic stem cell transplantation for neuroblastoma Perspective

REDUCED-INTENSITY AlloSCT In recent years, several groups of investigators have developed reduced-intensity conditioning regimens that lead to engraftment of donor lymphoid and hematopoietic stem cells without the extra-hematopoietic toxicities of standard myeloablative conditioning, while conserving the graft-versus-leukemia (GVL) or GVT effect. The reduced regimen-related toxicity may make reduced-intensity alloSCT (RI alloSCT) particularly suitable for patients at high-risk of regimen-related mortality, especially previous HDCT/autoSCT recipients. In adults, striking GVT effects after RI alloSCT have been described in refractory breast cancer and renal cell carcinoma [2]. Currently, the number of studies employing RI alloSCT for NB is very small.
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Chronic graft versus host disease with small bowel obstruction after unrelated hematopoietic stem cell transplantation in a patient with acute myeloid leukemia

Chronic graft versus host disease with small bowel obstruction after unrelated hematopoietic stem cell transplantation in a patient with acute myeloid leukemia

Received on September 7, 2011 Revised on October 7, 2011 Accepted on February 20, 2012 Chronic graft versus host disease (GVHD) is a frequent complication after allogeneic hem- atopoietic stem cell transplantation (HSCT), but simultaneous small bowel obstruction is rare. Here, we report a child with acute myeloid leukemia who received an allogeneic HSCT from an unrelated matched donor. After HSCT, the patient developed severe chronic GVHD involving the small intestine, leading to obstruction of the terminal ileum. Small bowel resection was performed, and the symptoms improved without severe complications. Bowel obstruction should be considered as a possible complication of chronic GVHD; surgery may be a valuable corrective measure.
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Patient acceptability and efficacy of simeprevir and sofosbuvir in hepatitis C after allogeneic stem cell transplantation

Patient acceptability and efficacy of simeprevir and sofosbuvir in hepatitis C after allogeneic stem cell transplantation

Heeda ROZARIO* Clinical Research, National Medicity Hospital, India EP-90 Introduction: The treatment goal of chronic hepatitis C virus (HCV) infection is sustained virological response (SVR) and the com- bination of simeprevir (SMV) and sofosbuvir (SOF) has been well tolerated in various studies. The study aimed to assess the patient acceptability and response to SMV-SOF in allogenic stem cell transplant.

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The role of allogeneic hematopoietic stem cell transplantation in the four P medicine era

The role of allogeneic hematopoietic stem cell transplantation in the four P medicine era

leukemogenesis did not really translate into decisive advances in the outcome of leukemias and cancers, except for CML. On the other hand, a “rough” therapy such as allo-HSCT was confirmed to be the most powerful treatment for high-risk hematological malignancies, representing one of the best answer to patients’ need of cure. Analyzing the causes of the partial disappointment on the results of targeted therapies and growing satisfaction with allo-HSCT results, we want also to point out that attention needs to be paid to the relevance of psychological and social aspects related to these approaches, and that they should be considered in the era of 4P medicine.
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Is a cure for CML without allogeneic stem cell transplantation around the corner? Perspective

Is a cure for CML without allogeneic stem cell transplantation around the corner?

141 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. BLOOD RESEARCH Volume 49ㆍNumber 3ㆍSeptember 2014 http://dx.doi.org/10.5045/br.2014.49.3.141

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BLOOD RESEARCH

Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation

Establishment of secondary iron overload We used the SIO animal model, as previously described [17]. Recipient mice were injected intraperitoneally with 300 L (10 mg) of iron dextran (Sigma-Aldrich, St. Louis, MO) in PBS (phosphate buffer solution) for five consecutive days per week according to the cumulative iron dose. The ex- perimental design was for cumulative iron dose of 50 mg, 100 mg, and 200 mg, respectively. The placebo control group received the same volume of PBS. The mice were observed for 2 weeks in order to monitor their viability after iron loading until the next experiment. All experimental groups used at least six mice according to study design.
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Impact of previous invasive pulmonary aspergillosis on the outcome of allogeneic hematopoietic stem cell transplantation

Impact of previous invasive pulmonary aspergillosis on the outcome of allogeneic hematopoietic stem cell transplantation

Historically, AmB, which is an ergosterol-binding polyene involved in the disintegration of the fungal membrane, has been the major antifungal drug used in patients with invasive aspergillosis. In our retrospective study, all 22 patients re- ceived amphotericin-based regimens for the treatment of pre-transplant IPA. Recent drug development has shown that lipid-bound formulations of AmB exhibit the same mi- crobiological activities and are also well-tolerated. Therefore, voriconazole is currently considered the drug of choice for the treatment of IA [17]. Despite the subsequent profound bone marrow suppression, positive outcomes are increasingly being achieved with the early and aggressive surgical man- agement of IPA [18]. One study examined 6 patients aged 2–15 years old who developed significant fungal infection of the lungs before or after undergoing bone marrow trans- plant [19]. Survival following bone marrow transplant was achieved for 6 and 11 months in patients who underwent lung resection before the transplant, and for 24, 30, 39, and 60 days in patients who underwent lung resection after the transplant. In our study, 3 patients underwent additional surgical resection before the HSCT, and IPA did not recur after HSCT in these patients.
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