Gut Microbiota in Graft-versus-Host Disease

Gut microbiota inhabit the host gastrointestinal (GI) tract and play roles in many aspects of metabolic and immunologic homeostasis. Understanding about gut microbiota composition in health and disease is accumulating with the advances in gene sequencing technology. Graft-versus-host disease (GVHD) is a major complication after allogenic bone marrow transplantation (allo-BMT), a gold standard clinical procedure to treat hematologic disorders such as leukemia and lymphomas. Recent studies have shown that a disturbance in the gut microbiota affects GVHD prognosis. Decrease in a compositional diversity is suggested as an independent predictor of GVHD and colonization of noncommensal Enterococcus is shown to be involved in unpleasant treatment outcomes. This article describes current understanding about allo-BMT-induced gut microbiota changes and its involvement in the incidence of GVHD. In addition, several putative therapeutic strategies to decrease GVHD-related mortality after allo-BMT are discussed.

HLA Mismatch Allogeneic Blood and Marrow Transplantation / 대한내과학회지

A full haplotype mismatch or mismatched unrelated donor transplantation nowadays are well being focused on, as main alternative donor tools for acute leukemia patients in desperate need of allogeneic blood and marrow transplantation (BMT), the ability to overcome various posttransplant complications by adopting the T-cell replete technique in reality. Increasing numbers of allogeneic BMT in good clinical status are largely because it's the best post-remission therapy especially for many patients with acute leukemias. Due to the problems of unavailable donors at appropriate clinical condition and the process of long duration of donor searching step with relatively much higher cost, some of physicians have indulged in haploidentical BMT rather than mismatched unrelated BMT. Both myeloablative and reduced intensity conditioning regimens for mismatched BMT with T-cell replete or T-cell depletion method have been exploited worldwide. Most of all, Asian countries have experienced lower rates of severe acute and chronic GvHD, graft failure, and impressively low transplant-related mortality with longer follow-up duration. Also, we need many future trials to compare outcomes between these two transplant modalities with cord blood transplant in various diseased patient populations.

Degradation of Benzo [a] Pyrene by a novel strain Bacillus subtilis BMT4i (MTCC 9447)

Benzo [a] Pyrene (BaP) is a highly recalcitrant, polycyclic aromatic hydrocarbon (PAH) with high genotoxicity and carcinogenicity. It is formed and released into the environment due to incomplete combustion of fossil fuel and various anthropogenic activities including cigarette smoke and automobile exhausts. The aim of present study is to isolate bacteria which can degrade BaP as a sole source of carbon and energy. We have isolated a novel strain BMT4i (MTCC 9447) of Bacillus subtilis from automobile contaminated soil using BaP (50 ìg /ml) as the sole source of carbon and energy in basal salt mineral (BSM) medium. The growth kinetics of BMT4i was studied using CFU method which revealed that BMT4i is able to survive in BaP-BSM medium up to 40 days attaining its peak growth (10(29) fold increase in cell number) on 7 days of incubation. The BaP degradation kinetics of BMT4i was studied using High Performance Liquid Chromatography (HPLC) analysis of BaP biodegradation products. BMT4i started degrading BaP after 24 hours and continued up to 28 days achieving maximum degradation of approximately 84.66 percent. The above findings inferred that BMT4i is a very efficient degrader of BaP. To our best of knowledge, this is the first report showing utilization of BaP as a sole source of carbon and energy by bacteria. In addition, BMT4i can degrade a wide range of PAHs including naphthalene, anthracene, and dibenzothiophene therefore, it could serve as a better candidate for bioremediation of PAHs contaminated sites.

Clinical profile of adrenoleukodysrophy.

X-linked Adrenoleukodystrophy (ALD) is the most common of the peroxisomal disorder and is associated with functional defect of the very long chain fatty acid (VLCFA) oxidation leading to the accumulation of VLCFA in the white matter and adrenal cortex. Retrospective evaluation of medical records of ALD patients were carried out. In all the 5 patients the duration of the symptoms varied from 1-7 years. Most of them presented with Addisonian crisis (4/5) and hyperpigmentation (5/5), white half of them (3/5) had neurological symptoms. All patients had biochemical evidence of the adrenal insufficiency. All siblings of patients should be screened for the possibility of ALD with VLCFA.

Study the role of transforming growth factor ?_1 in acute graft-versus-host-disease after allogeneic bone marrow transplantation in murine model / 中国实用内科杂志

Objective The study was aimed to investigate the effects of transforming growth factor beta1(TGF-?1)on acute graft-versus-host disease(aGVHD)after allogeneic bone marrow transplantation(allo-BMT).Methods The recipient was male BABL/C.The donor was male C57BL/6.The murine model of aGVHD had been established by allo-BMT with donor derived T cells.There were four groups in this study:control group,radiation group,transplantation control group and TGF-?1 group.The mice in TGF-?1 group were administered TGF-?1[1 ?g/(kg?d)]subcutaneously two days before transplantation until seven days after it.Results The study showed that the survival time of TGF-?1 group was significantly longer than the transplantation control group,and the aGVHD pathological changes were milder in TGF-?1 group than in transplantation control group.Seven days after transplantation,the level of IL-2 of TGF-?1 group was higher than control group,but significantly lower than transplantation control group.The level of IL-10 of TGF-?1 group was significantly higher than transplantation control group.Conclusion TGF-?1 can prevent the lethal aGVHD and raise the survival rate after allo-BMT in murine model.It may prevent the lethal aGVHD by accommodating the Th1 and Th2 cytokine level in vivo.

A Case of Eosinophilic Folliculitis after Allogenic Bone Marrow Transplantatino in Acute Myelogenous Leukemia

Eosinophilic folliculitis (EF) is regarded as a variant of eosinophilic pustular folliculitis (EPF), because it has a few distinctive clinical features different from those of EPF. EF is generally associated with systemic disorders, such as acquired immunodeficiency syndrome (AIDS) and hematologic malignancies. We have recently experienced a case of EF occurring in a 40 year-old male patient treated with allogenic bone marrow transplantation (BMT) for acute myelogenous leukemia(AML) and achieved a good clinical outcome after a short course of systemic corticosteroid therapy. The immunologic aberration resulting from systemic diseases may play a role in the development of EF.

Serial Assessment of Cardiac Function and Morhology Using Transthoracic Echocardiography after Bone Marrow Transplatiation

PURPOSE: Bone Marrow Transplantation (BMT) is very stressful treatment to the patients' hearts. The aim of this study was to evaluate the serial change of cardiac function and morphology on echocardiography and to propose the guidelines of echocardiographic monitoring in BMT patients. METHOD: We divided the 64 patients (M:F=42:22, mean age 33+/-9, 25 AML, 8 ALL, 19 CML, 12 others) with hematologic diseases into early group (M:F=22:7, mean age=33+/-9) whose follow up echocardiograms were taken within 90 days, and late group (M:F=20:15, mean age=33+/-8) whose follow up echocardiograms were taken beyond 90 days after BMT. In both groups, changes of left ventricular dimensions, ejection fraction, wall thickness, E/A ratio and deceleration time (DT) were measured before and after BMT. RESULTS: Cardiac complications were observed in 18 pateints after BMT. The pericardial effusion in 6, benign arrhythmias in 6, including sinus arrhythmia, premature ventricular contraction, premature atrial contraction developed in the early group, but 5 of 6 patients who had ejection fraction less than 40% were in the late group. After BMT, the thickness of interventricular septum and left ventricular posterior wall was significantly increased (p<0.05) and ejection fraction and E/A ratio was significantly decreased (p<0.05, respectively) in the early group. In the late group the thickness of interventricular septum returned to normal range, but ejection fraction was significantly decreased (p<0.05) and deceleration time significantly (p<0.05) shortened. CONCLUSION: This study shows that the early cardiac change after BMT is mainly decrease of LV systolic function with hypertrophy and the late change is not only decrease of systolic function but also change of diastolic parameters. Therefore the serial assessment of cardiac function and morphology using transthoracic echocardiography is essential for the early diagnosis of cardiac toxicity, especially early after BMT.

Application of HLA-DRB、DPB1 genotyping by PCR-SSP、RFLP for allogeneic bone marrow transplantation / 中国免疫学杂志

Objective:To investigate the feasibility of clinical application of HLA-DRB,DPB1 genotyping by PCR-SSP,RFLP for alloge-neic bone marrow transplantation(Allo-BMT) .Methods: Corresponding to each of the DRB alleles, nineteen different pairs of sequence specific primers were used to PCR amplify them from twenty samples in both recipients and donors and their amplified products were directly analyzed on agarose gel. At the same time, a pair of primer was used to PCR amplify the second exon of DPB1 and the restriction fragment length polymorphisms were analyzed on PAGE after their PCR products were separately digested by ten endonucleases. Results: Each DRB was typed in according to its clear and visualized electrophoresis band; the DPB1 genotype was also determined by analysis of all codes representing polymorphism fragment band with a computer. Four couples of recipient and donor were matched. Conclusion:PCR-SSP and RFLP are rapid, accurate and reliable genotyping approaches for Allo-BMT.

The Effect of Bone Marrow Transplantation on Bone Mineral Metabolism: 2 - Year Prospective Study / 대한내분비학회지

BACKGROUND: Loss of bone mass is usually detected after bone marrow transplantation (BMT), especially during the early post-transplant period. But little is known about the long-term effects of BMT on bone mineral metabolism. METHODS: We have investigated prospectively 12 patients undergoing BMT (4 autologous, 8 allogeneic) for hematologic diseases (8 leukemia, 3 SAA, 1 MDS). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and bone turnover markers (osteocalcin and ICTP) were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months and 1, 2 years thereafter. Bone mineral density (BMD) was measured with DEXA (Dual Energy X-ray Absorptiometry) before BMT, 1 year and 2 year after BMT. In patients with amenorrbea, hormone replacement therapy was started from around 1 year after BMT RESULTS: 1. The mean bone loss in the lumbar spine, calculated as the percent change from the baseline to the level at 1 year and 2 year was 7.3% and 1.9%, respectively. The mean bone loss in the total proximal femur from the baseline to the level at 1 year and 2 year was 8.0% and 8.3% respectively. 2. The serum ICTP increased progressively until four weeks after BMT. Thereafter, it decreased gradually to reach basal values after one year and thereafter no more change until 2 year. Serum osteocalcin decreased progressively until three weeks after BMT. After that, it increased and reached basal values after 3 months. Osteocalcin increased at 6 month transiently but thereafter, it decreased to the level of slightly above basal value at 2 year. 3. Patients who were treated with TBI or pateints with GVHD had a tendency of lower BMD at l year and 2 year after BMT than those of patients without TBI or GVHD. 4. Eight out of nine women went into a menopausal state immediately after BMT and remained amenorrhea, evidenced by high gonadotropins and low estradiol levels. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. CONCLUSION: The rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in bone loss after BMT. The efficacy of HRT for the correction of hypogonadism and bone loss was evidenced by 2 year BMD which was much more increased compared to 1 year BMD, especially in vertebra.

Ovarian Recovery after Bone Marrow Transplantation in Aplastic Anemia / 대한산부인과학회잡지

OBJECTIVE: Ovarian failure is often common complication by the conditioning protocol used for bone marrow transplantation (BMT). To determine the frequency of recovery of ovarian function after allo-BMT and the major factor that predict recovery, we monitored ovarian function in 24 premenopausal women METHOD: Twenty-four women met the inclusion criteria, which were (1) moderate to severe aplastic anemia before BMT, (2) disease-free at least 18 month after transplantation, (3) age younger than 40 years and more than 3 years after menarche at transplantation and (4) regular menstrual periods before transplantation. Recovery of ovarian function was determined by regular menses without menopausal symptom and sign. we divided conditioning regimen to two groups, Group I : cytoxan alone(n=17), Group II : cytoxan plus total body irradiation (TBI)(n=7). RESULTS: All women became amenorrhea after BMT and the clinical characteristics were not significant between two groups. 17 patients who received only cytoxan all recovered ovarian function between 1 to 14 months(median : 7.28) after BMT. The median age at BMT of women with regained ovarian function was 26 years (range, 21 to 33) versus 30 (range, 21 to 37) for those who did not. The age at transplantation was not significant between two groups in our study and the most predictive independent factor in ovarian recovery is the presence of total body irradiation. None of women who received TBI regained ovarian function during 19-49 month follow up. CONCLUSION: Gonadal insufficiency due to pre-BMT conditioning is more severe in radiation based regimen than cytoxan alone. therefore, we recommend early hormone replacement therapy in radiation treated women to prevent the complication of premature menopause.

Correlation between Progenitor Cell Dose and the Rate of Engraftment in Autologous Peripheral Blood Stem Cell Transplantation and Allogeneic Bone Marrow Transplantation / 대한수혈학회지

BACKGROUND: Bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT) following high dose chemotherapy has been an important therapeutic option for patients with hematologic malignancies or some solid tumors. The number of progenitor cells in the collection products has been used to determine the optimum time to stop the collections and to predict the hematopoietic engraftment after transplantation. In this study, we investigated the relationship between end-product cell counts measured by different methods and the influence of the infused cell dose on the engraftment rate. METHODS: Twenty five patients receiving autologous PBSCT and 25 patients receiving allogeneic BMT were studied. The number of total nucleated cells (TNC), of mononuclear cells (MNC), of CD34+ cells, and of CFU-GM (colony-forming unit-granulocyte monocyte) colonies were measured in each collection product. The number of days required to achieve an absolute neutrophil count (ANC) of 0.5x109/L with TNC count of 1.0x109/L and platelet count of 20x109/L without transfusions was taken as an arbitrary measure of the engraftment rate. RESLUTS: A close correlation between CD34+ cells/kg and CFU-GM/kg was observed in both collection products (p<0.05). However, MNC/kg also showed significant correlations with CD34+ cells/kg and CFU-GM/kg in allogeneic bone marrow collection products (p<0.05). The CFU-GM amount in the PBSC products was greater than that in the bone marrow collection products (p<0.05). Time to engraftment was a median of 14 (range 9-50) days in autologous PBSCT group, but 29 (range 17-57) days in allogeneic BMT group. In autologous PBSCT, infused CD34+ cells/kg and CFU-GM/kg correlated significantly with ANC recovery (p<0.05). CONCLUSIONS: The number of CD34+ cells was correlated with that of CFU-GM in the collection products, and the infused cell doses showed positive relation to the engraftment rate in autologous PBSCT. These findings suggest that measurement of CD34+ cell counts alone would be a sufficient parameter to predict the engraftment rate in autologous PBSCT.

Experience of Balloon Matas Test (BMT) in Carotid Artery Surgery

A temporary balloon occlusion of internal carotid artery (ICA) was performed in 3 patients for carotid artery endarterectomy and 1 patient require sacrifice ICA with neck malignancy. EEG monitoring and neurologic evaluation was done during the test. In one patient who has bilateral ICA stenosis more than 95% shows slurred speech and aphasia during test. Another 3 patients shows no clinical change during test, and operation was done without shunt. There were no postoperative neurologic complication. We believe that preoperative balloon occlusion of ICA provide another helpful criteria to decide using shunt. But it needs another hemodynamic analysis tool according to other's report.

Reconstitution of Bone Marrow after Allogeneic and Autologous Bone Marrow Transplantation / 대한혈액학회지

BACKGROUND: The bone marrow transplantation (BMT) is an effective treatment for patients with several hematologic diseases. However, most studies for immune reconstitution after BMT are limited to immunophenotyping of lymphocytes in the peripheral blood and little information about cell surface antigen expression and distribution of the nucleated elements in the bone marrow after BMT have been published. To set up baseline data for bone marrow recovery after BMT, we investigated reconstitution of the bone marrow at 21th day after allogeneic and autologous BMT. METHODS: The flow cytometric analyses for 17 monoclonal antibodies in the 35 bone marrow transplant recipients (allogeneic BMT 25, autologous BMT 10) and 20 healthy donors of allogeneic BMT were performed. The percentage of positive cell population was calculated in the gated region and compared data for BMT vs normal controls and allogeneic vs autologous BMT. RESULTS: CD8+ T cell and CD56+ NK cell were the first signs of immunological recovery at 21th day after BMT, whereas the CD4+ subsets were significantly decreased. These findings were prominent in the autologous BMT. After BMT, the CD2+CD5- cell population was characteristically increased. All B cell markers were decreased and most lympocytes were expressed HLA-DR. The donor's immunophenotypes before BMT did not correlate with the recipient's immunophenotypes after BMT. CONCLUSIONS: We demonstrated that the CD8+ T cells and NK cells were main cell populations in the bone marrow for primary immunological defences at 21th day after BMT and these findings were more distinct in the autologous BMT than the allogeneic BMT. It indicated that there were more rapid reconstitution in the autologous BMT. The B cell recovery was delayed rather than T cell and increased CD2+CD5- cell population was characteristic finding in post-BMT.

THE STRATEGIES FOR PREVENTING AND TREATING INFECTION OF CYTOMEGALOVIRUS IN BONE MARROW TRANSPLANTATION / 药物分析学报

In bone marrow transplantation (BMT), cytomegalovirus (CMV) interstitial pneumonitis (IP) is one of the most dangerous complications, which has been the first important cause to lead the failure of BMT. At present, there is no effective and specific therapy for CMV-IP, therefore how to prevent CMV infection effectively is a top task. From 1991 to 1996, we used comprehensive steps to prevent CMV-IP in BMT, and none of 14 patients developed CMV-IP. The preventing results that we achieved by using the steps were quite satisfied.

The Short-term Effects of Bone Marrow Transplantation on Bone Metabolism / 대한내분비학회지

BACKGROUND: The organ transplantation becomes the management of choice for many patients with chronic and life threatening heart, liver, kidney, bone marrow, and pancreatic diseases. A new set of side effects unique to this groups of patients has become recognized. Bone disease is one of these complications. It is well known that there is an interplay between the cells in the bone marrow and the surrounding bone tissue. Marrow stromal cells include the progenitors of the osteoblastic lineage are the sources of effector molecules that support and regulate both hematopoiesis and bone remodeling. But little is known about the effects of myeloablative treatment followed by bone marrow transplantation(BMT) on bone metabolism. METHODS: We have investigated prospectively in 29 patients undergoing BMT(4 autologous, 25 allogenic) for hematologic diseases(19 leukemia, 9 severe aplastic anemia, 1 myelodyspoietic syndrome). Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones and biochemical markers of bone turnover(osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen(ICTP)] were measured. The samples were collected before BMT and 1, 2, 3, 4, 12 weeks, 6 months and 1 year thereafter. Bone mineral density was measured with DEXA(Dual Energy X-ray Absorptiometry) before and after 1 year of BMT. RESULTS: 1. ICIP was progressively increased until 4 weeks after BMT when peak values were reached. And then decreased thereafter and basal values were regained after 1 year. Osteocalcin was progressively decreased until 3 weeks after BMT when nadir values were reached. And then increased thereafter and basal values were regained after 3 months. No distinct differences were observed in serum biochemical turnover marker between both sexes and between patients who received total body irradiation and those who did not. 2. Lumbar BMD was 2.1% decreased from 1.113 +/- 0.132 g/cm to 1.089 +/- 0.137 g/cm, and femoral BMD was 6.2% decreased fiom 1.078 +/- 0.156 g/cm to 1.011 +/- 0.157 g/cm. 3. 92% of the women (11/12) became menopausal manifested by high gonadotropin and low estradiol levels immediately after BMT. In contrast to women, gonadotropins and testosterone levels were not changed significantly in men after BMT. CONCLUSION: The rapid impairment of bone formation and also increase in bone resorption, as mirrored by the biochemical markers in this study, might play a role for the post-BMT bone loss. Further studies over many patients with a longer follow up will be needed.

Successful treatment with ganciclovir for cytomegalovirus duodenitis following allogenic bone marrow transplantation

Cytomegalovirus(CMV) disease is a major cause of morbidity and mortality in immunocompromised patients. CMV enteritis should be considered when nausea and vomiting continue 3 to 4 weeks after bone marrow transplantation(BMT). The treatment of CMV enteritis is not well established. We report a CMV duodenitis patient following allogenic bone marrow transplantation. The patient had prolonged nausea and vomiting for 5 weeks after bone marrow transplantation and CMV duodenitis was diagnosed by the gastroduodenoscopic mucosal biopsy which showed cytomegalic cells. Ganciclovir treatment for 3 weeks resulted in the resolution of symptoms and promoted healing of the lesion. The patient was free of CMV infection until 288 days after allogenic BMT without maintenance ganciclovir treatment.

Fluorescence in situ Hybridization using Chromosome X alpha-Satellite Probe To Evaluate Engraftment and To Monitor Residual Disease after Bone Marrow Transplantation / 대한임상병리학회지

BACKGROUND: Several methods have been used to evaluate the engraftment and to monitor residual disease after bone marrow transplantation (BMT). Among them, karyotyping have been useful in gauging engraftment following opposite sex BMT. More recently, fluorescence in situ hybridization (FISH) has also been applied to determine engraftment and residual status. In order to establish the utility of this method in clinical practice, we have evaluated the data from FISH and several methods. METHODS: We performed FISH using chromosome X alpha-satellite probe (Oncor , USA) on twenty eight peripheral blood and nine bone marrow nuclear cells from eleven patients who underwent sex mis-matched transplant and from a patient who had a loss of X chromosome. RESULTS: In nine patients with well engrafted BMT, signals of host cells showed less than 5% in all patients, evaluated 21-210 days post-transplant. Mixed chimerism was detected in six patients; transiently in early post-transplant period in four, in a patient with engraftment failure, and in a patient with relapse, respectively. CONCLUSION: FISH using X probe is a rapid, quantitative and sensitive 'interphase cytogenetic method' for the evaluation of engraftment and monitoring of residual disease following sex mis-matched BMT or BMT in a patient with a loss of X chromosome; It is especially useful in early post-transplant period when ony a few cells are available during severe cytopenia.

Rh antigen determination: A marker for erythroid engraftment and proliferation after ABO compatible allogeneic bone marrow transplantation / 대한수혈학회지

BACKGROUNDS: It is useful to estimate the percentage of donor's red cell population in the recipient's blood for determinating the erythroid engraftment and proliferation after allogeneic bone marrow transplantation (BMT). We evaluate the usefulness of Rh antigen determination by flow cytometry and agglutination method for the decision of erythroid engraftment and proliferation after ABO compatible BMT. METHODS: In the case of ABO compatible, Rh mismatched BMT (donor; ccDEE, recipient; Ccdee), the percentage of donor typed red cells was estimated by the flow cytometric analysis using polyclonal anti-D sera during the follow-up period by weekly. At the same time, the agglutination test using polyclonal/monoclonal anti-D sera and monoclonal anti-E sera were performed. RESULTS: At 4th week after BMT, the percentage of RhD positive-donor typed red cells was increased up to 5% in flow cytometric analysis, whereas the agglutination test did not reveal any changes of agglutination in reaction using anti-D and anti-E antibodies. At 5th week after BMT, about 10% of RhD positive cells were identified by flow cytometry, the agglutination test for D and E antigen determination revealed the changes of agglutination strength at first. At 12th week after BMT, 95% of patient's red cells converted RhD positive in flow cytometric analysis. CONCLUSIONS: Rh antigen determinations by flow cytometric analysis and agglutination test are useful to estimate erythroid engraftment and proliferation after ABO compatible BMT.

A Preliminary Report of Busulfan, Melphalan and Thiotepa or TBI-containing Bi-alkylator Chemotherapy as a Preparative Regimen for Allogeneic Bone Marrow Transplantation in Refractory or Relapsed Acute Leukemias / 대한암학회지

PURPOSE: We assessed the three-alkylator combination of busulfan, melphalan and thiotepa or TBI, melphalan and thiotepa conditioning for allogeneic stem cell transplantation in 7 adult patients with refractory or relapsed acute leukemias. MATERIALS AND METHODS: Six patients were transplanted for acute myeloid leukemia, one for acute lymphoblastic leukemia and included 5 of relapsed refractory, 2 of relapsed after first-BMT. All but 1 cases received G-CSF stimulated CD34+ allogeneic peripheral blood progenitor cells (PBPCs) in addition to stimulated allogeneic marrow. RESULTS: All patients except one engrafted (median time to ANC >0.5 10 (9)/L=11days, to platelets >30 X 10 (9)/L=14 days) successfully and complete remission was obtained in 6 patients. Grade I-II acute GVHD and controllable regimen-related toxicity especially oral mucositis (grade II-III) developed in all cases, but 2 patients including one second- allogeneic BMT patient expired early by transplant-related toxicity of hepatic or multiorgan failure along the course of sepsis. CONCLUSION: Although the observation period on these cases are limited, the data presented show that the combination of busulfan, melphalan and thiotepa is tolerable as a preparative regimen for allogeneic marrow transplantation in high-risk leukemic patients. We think that these encouraging results need to be confirmed in prospective studies in the future.

Isoagglutinin Titer in Major ABO Incompatible Bone Marrow Transplantation / 대한수혈학회지

BACKGROUND: Major ABO incompatibility between donor and recipient is not a barrier for successful bone marrow transplantation(BMT). However, isoagglutinins could cause serious adverse effects, such as engraftment failure, delayed hematopoiesis and delayed hamolysis. It is important to detect these complications and bone marrow engraftment at an early stage for appropriate management. We have investigated the usefulness of isoagglutinin titer in major ABO incompatible BMT. METHODS: During April, 1996 to September, 1997, thirteen cases underwent major ABO-incompatible BMT at Asan Medical Center. We reviewed their medical records and performed ABO blood typing, IgM and IgG isoagglutinin titration, direct antiglubulin test and test for A and B transferase activities. RESULTS: Isoagglutinins against the donor antigen disappeared in 9 cases, decreased in 3 cases and persisted in 1 case. One patient who had persistent isoagglutinin titer had not had a bone marrow engraftment. The average time for anti-A isoagglutinin titer to disappear was 167.8 days(range; 90-281) and for anti-B was 116.8 days(range; 30-276). Eleven out of 13 cases, the RBCs of donor type appeared. On the average, RBCs of group A appeared later than RBCs of group B (112.7 +/- 99.6 days vs. 71.4 +/- 92.0 days, P>0.05). In 7 out of 8 cases that were done the A and B transferases test, the donordegrees empty set s RBC was produced but very little or none of the donor type transferase appeared in the serum. CONCLUSION: In order to determine the erythroid engraftment after the major ABO incompatible BMT, it is necessary to check the isoagglutinin titer periodically.