• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.96-101
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• 2012

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the optimal curative treatment for acute myeloid leukemia (AML), but some patients develop bone marrow relapse due to remnant leukemia, and few patients develop extramedullary relapse without bone marrow relapse. Isolated extramedullary relapse (IMER) is defined as extramedullary relapse without bone marrow relapse. IMER has been reported in various sites, including the skin, soft tissue, and central nervous system(CNS). Isolated CNS relapse is relatively rare and is associated with poor prognosis due to the absence of an optimal treatment for it. Reported herein is a case involving an adult AML woman who suffered from isolated extramedullary relapse in the CNS after allogeneic HSCT. She was treated with intrathecal chemotherapy and whole-brain and spine radiotherapy, followed by systemic chemotherapy. She is currently well, with no evidence of leukemia recurrence for over six years.

• Journal of Yeungnam Medical Science
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• v.32 no.2
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• pp.98-101
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• 2015

Bronchiolitis obliterans (BO), which is associated with graft-versus-host disease after allogenic hematopoietic stem cell transplantation, is a major obstacle to survival after bone marrow transplantation due to its gradual progress, eventually leading to respiratory failure. Pumpless extracorporeal interventional lung assist (iLA) is effective in treatment of reversible hypercapnic respiratory failure. In this paper, we present a 23-year-old female patient who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) for acute lymphocytic leukemia. After 6 months, she complained of shortness of breath and was diagnosed with BO. Five months later, she developed an upper respiratory tract infection that worsened her BO and caused life-threatening hypercapnia. Since mechanical ventilation failed to eliminate $CO_2$ effectively, iLA was applied as rescue therapy. Her hypercapnia and respiratory acidosis showed significant improvement within a few hours, and she was successfully weaned off iLA after 12 days. This is the first case report of iLA application for temporarily aggravated hypercapnia of PBSCT-associated BO followed by successful weaning. This rescue therapy should be considered in ventilator-refractory reversible hypercapnia in BO patients.

• Tuberculosis and Respiratory Diseases
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• v.71 no.6
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• pp.459-463
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• 2011

Pulmonary complications occur in 40~60% of patients who receive hematopoietic stem cell transplantation (HSCT) and are a source of substantial morbidity and mortality. Acute eosinophilic pneumonia (AEP) is an uncommon, non-infectious pulmonary complication occurring in HSCT recipients. We now report the case of a 52-year-old man with AEP who was treated with allogenic HSCT due to acute myeloid leukemia. He complained of fever, cough and dyspnea 390 days after allogenic HSCT. He also had skin and hepatic graft versus host disease (GVHD). Hypoxemia, diffuse pulmonary infiltrates on a chest x-ray and eosinophilia in bronchoalveolar lavage fluid were also noted in several tests. His symptoms, pulmonary infiltrates, hepatic dysfunction and skin lesions rapidly improved after treatment with corticosteroid therapy. Our case supports the idea that AEP is a late phase non-infectious pulmonary complication and one of the manifestations of chronic GVHD.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.245-251
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• 2016

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) ($23{\times}ABW^{0.5}mg\;daily$) targeting an area under the concentration-time curve (AUC) of $5924{\mu}M{\cdot}min$. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC ($AUC_{PRED}$). The accuracy and precision of the $AUC_{PRED}$ values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of $5924{\mu}M{\cdot}min$. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of $AUC_{PRED}$ were -5.8% and 20.6%, respectively, in the conventional dosing group and -2.1% and 14.0%, respectively, in the new dosing scheme group. These findings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.

• Korean Journal of Clinical Laboratory Science
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• v.38 no.1
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• pp.9-15
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• 2006

Peripheral bood stem cell collection (PBSCC), including peripheral blood stem cell transplantation (PBSCT), has been utilized worldwide as a very beneficial treatment method instead of allogenic Bone Marrow Transplantation (BMT) because it has many advantages such as rapid bone marrow engraftment and hematopoietic recovery, easy and safe accessibility and lower risk of rejection compared with allogenic BMT. In order to identify most the observable parameter in PBSCC, we analyzed various hematological parameters before and after PBSCC, and evaluated the correlation between the time of bone marrow engraftment and the number of CD34+ cells. Thirteen patients, who underwent 54 PBSCCs from January, 2003 to August, 2004 at Chungnam National University Hospital due to various systemic neoplasms, were analyzed in aspects of various hematological parameters including CD34+ cells using by Flow Cytometry (FCM). PBSCC harvests are described below: Mononuclear cells (MNC) $2.3{\pm}1.4{\times}10^8/kg$ and CD34+ cells $0.63{\pm}0.35{\times}10^6/kg$ on average, respectively. There was a statistical significance in Hb and Hct before and after PBSCC, but not in WBC and platelet counts. The period to reach the hematological bone marrow engraftment was 13.4(10~21) days and 19.5(11~38) days according to the criteria of absolute neutrophile counts (ANC) ${\geq}500/uL$ and platelet counts ${\geq}50,000/{\mu}L$ in peripheral blood, respectively. There was a significant correlation between the numbers of CD34+ cell and ANC (p<0.05), and a borderline significance between MNC and ANC (p=0.051). We found that a group of patients, who were infused with CD34+ cells more than $3.5{\times}10^6/kg$, reached more rapidly the period of bone marrow engraftment in platelet counts (p=0.040). This present study suggested that Hb and Hct were the most useful parameters and should be closely monitored before and after PBSCC, that a PBSCT with the dosage of more than $3.5{\times}10^6/kg$ of CD34+ cells was needed to perform successful bone marrow engraftment, and additionally that platelet counts could be more useful in indicating bone marrow engraftment than ANC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7415-7419
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• 2013

The diagnosis of latent Mycobacterium tuberculosis infection (LTBI) is recommended in hematological malignancy patients and before hematopoietic stem cell transplantation (Guidelines for the prevention and management of infectious complications of solid organ transplantation, 2004). Compared to traditional methods such as tuberculin skin test (TST), T-SPOT.TB has been shown to be more specific. In the present study we enrolled 536 patients for whom T-SPOT.TB was performed, among which 295 patients also received the TST test. The agreement (79%) between T-SPOT.TB and TST was poor (x=0.274, P<0.001). The patients with positive T-SPOT.TB results numbered 62 (11.6%), in which only 20 (48.8%) of the 41 receiving the TST test had positive results. A majority of the patients with T-SPOT.TB positive results had some other evidence ofTB, such as TB history, clinical symptoms and an abnormal chest CT scan. Active TB was found in 9 patients, in which 2 had negative TST results. We followed up the patients and no one developed active TB. Our study suggested that the T-SPOT.TB may be more useful for screening LTBI and active TB in hematological malignancy patients and hematopoietic stem cell transplant recipients than the TST test.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.370-375
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• 2002

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.

• Childhood Kidney Diseases
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• v.26 no.1
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• pp.11-17
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• 2022

BK polyomavirus (BKPyV) is a ubiquitous virus residing in the kidney tubules and is clinically significant only in immunocompromised patients. In clinical practice, BKPyV is a causative pathogen of BKPyV-associated nephropathy (BKVAN) in kidney allograft recipients or hemorrhagic cystitis of hematopoietic stem cell transplant recipients. Currently, there is no effective treatment for BKVAN; therefore, careful monitoring and prudent modification of immunosuppression are necessary to prevent BKVAN. In this article, the epidemiology, pathophysiology, and current management strategies for BKVAN are reviewed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4215-4220
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• 2012

AML (Acute myeloid leukemia) is a form of blood cancer where growth of myeloid cells occurs in the bone marrow. The prognosis is poor in general for many reasons. One is the presence of leukaemia-specific recognition markers such as FLT3 (fms-like tyrosine kinase 3). Another name of FLT3 is stem cell tyrosine kinase-1 (STK1), which is known to take part in proliferation, differentiation and apoptosis of hematopoietic cells, usually being present on haemopoietic progenitor cells in the bone marrow. FLT3 act as an independent prognostic factor for AML. Although a vast literature is available about the association of FLT3 with AML there still is a need of a brief up to date overview which draw a clear picture about this association and their effect on overall survival.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.150-155
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• 2003

Background: We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). Methods: We used 4 to 6 week old Balb/c ($H-2^d$, recipient), and C3H/He ($H-2^k$, donor) mice. Total body irradiated recipients received $1{\times}10^7$ bone marrow cells (BM) and $0.5{\times}10^7$ splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with $1{\times}10^7$ rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. Results: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. Conclusion: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.