Nursing care of a patient with severe aplastic anemia type Ⅱ treated with umbilical cord blood transfusion sequentially combined with second haploid allogeneic bone marrow transplantation / 中国实用护理杂志

Objective To summarize the nursing care for one successful haploidentical allogeneic bone marrow transplantation (haplo-BMT) for one patient with severe aplastic anemia type-Ⅱ (SAA-Ⅱ). The patient accepted an umbilical cord blood transfusion sequentially combined with the second haplo-BMT after an engraftment failure of the first haplo-BMT. The experience of nursing care will be discussed and shared for patients with a second haplo-BMT. Methods The comprehensive nursing cares were utilized during haplo-BMT, it included preventive measures for secondary infections, closely control of side effects, promptly nursing intervention for gastrointestinal mucositis, hemorrhagic cystitis and epilepsy, psychological nursing for appeasing emotional variations, and addition of intravenous indwelling needle if necessary. Results The patient achieved a successful stem cell engraftment and survived a long-term granulopenia (granulocytes＜0.1×109/L) which lasted for 52 days with a recovery of varied complications. Conclusion The comprehensive nursing care can reduce the risk for secondary infections and other complications, it shed a new light on second allogeneic bone marrow transplantation for complicated patients

Induced Pluripotent Stem Cells-derived chimeric Thymus transplantation enhances T cells Reconstitution and prevents GVHD in Murine after allogeneic Bone Marrow Transplantation / 实用医学杂志

Objective To explore the effects of iPS cells-derived chimeric thymus transplantation on T cells reconstitution and graft versus host disease of murine after allo-BMT. Methods iPS cells-derived chimeric thymus was grafted under the renal capsules of mice after allogeneic IBM-BMT. The mice were divided into three groups:IBM-BMT group, IBM-BMT+TT group and IBM-BMT+DLI group. Four weeks after BMT, T lymphocyte subsets in the peripheral blood were analyzed by flow cytometry, the degree and pathological examination of GVHD were observed, respectively. Results Percentage of CD8+T cells in IBM-BMT group, IBM-BMT+TT group and IBM-BMT+DLI group was(5.52 ± 0.83)%,(11.10 ± 1.49)%and(8.49 ± 0.82)%respectively, there was signifi-cant difference between pairwise comparisons(P<0.05), and percentage of CD4 + T cells of the peripheral blood in IBM-BMT+TT group(9.60 ± 0.69)%was significantly higher than IBM-BMT group(6.42 ± 1.40)%and IBM-BMT+DLI group(8.07 ± 0.65)%(P<0.05) . IBM-BMT group and IBM-BMT+TT group showed less clinical and histopathological scoring of GVHD than IBM-BMT + DLI group. Conclusion iPS cells-derived chimeric thymus transplantation could effectively accelerate T cells reconstitution and prevent GVHD after allo-BMT.

Human Bone Marrow Subpopulations Sustain Human Islet Function and Viability In vitro.

Aims: Allogeneic bone marrow (BM) has been shown to support human islet survival and function in long-term culture by initiating human islet vascularization and β-cell regeneration. Various BM subpopulations may play different roles in human islet functions and survival. In this paper we investigated the effects of BM and its subpopulations, endothelial progenitor cells (E) and mesenchymal (M) cells on human islet’s β-cell function and regeneration. Study Design: Isolation and identification of subpopulations from human bone marrow and culture with allogeneic human islet to investigate effects of different cell population on human islet function and regeneration. Place and Duration of Study: Department of Medicine, Center for Stem Cell & Diabetes Research, RWMC, Providence, RI, USA, between 2010 - 2014. Methodology: Human islets were distributed from Integrated Islet Distribution Program (IIDP) and human bone marrow (BM) was harvested by Bone marrow transplantation center at Roger Williams Hospital. BM subpopulation was identified cell surface markers through Fluorescenceactivated cell sorting, applied in flow cytometry (FACS), islet function was evaluated by human ELISA kit and β cell regeneration was evaluated by three methods of Cre-Loxp cell tracing, β cell sorting and RT-PCR for gene expression. Results: Four different BM and seven different islet donates contributed human tissues. We observed islet β-cell having self regeneration capability in short term culture (3~5 days) using a Cre-Loxp cell tracing. BM and its subtype E, M have similar benefits on β cell function during coculture with human islet comparison to islet only. However, only whole BM enables to sustain the capability of islet β-cell self regeneration resulting in increasing β cell population while single E and M individual do not significantly affect on that. Mechanism approach to explore β-cell self regeneration by evaluating transcription factor expressions, we found that BM significantly increases the activations of β-cell regeneration relative transcription factors, the LIM homeodomain protein (Isl1), homologue to zebrafish somite MAF1 (MAFa), the NK-homeodomain factor 6.1 (NKX6.1), the paired box family factors 6 (PAX6), insulin promoter factor 1 (IPF1) and kinesin family member 4A (KIF4a). Conclusion: These results suggest that BM and its derived M and E cells enable to support human islet β-cell function. However, only BM can sustain the capability of β-cell self regeneration through initiating β-cell transcriptional factors but not individual E and M cells suggesting pure E and M cells less supportive for islet long-term survival in vitro.

Establishment of an acute graft-versus-host disease animal model in EL4 T-cell leukemia/lymphoma mice / 中华实用儿科临床杂志

Objective To establish an acute graft-versus-host disease (aGVHD) model in EL4 T-cell leukemia/lymphoma mice,for providing experimental model to prevent aGVHD while maintaining graft-versus-leu1 mia (GVL) effect during allogeneic bone marrow transplantation (Allo-BMT).Methods Male BALB/c (H-2Kd)mice were used as donors and female C57BL/6(H-2Kb) mice were used as recipients.C57BL/6 hosts were given 9.5 Gy lethal total body irradiation at 4 hours prior to transplantation.Mice were randomly assigned into 3 groups and each group contained 17 recipients:The recipients in radiation group were injected with 0.2 mL RPMI 1640 as control.The recipients were injected with donor bone marrow cells (5 × 106/mouse) and splenocyte for aGVHD(5 × 106/mouse).The recipients in EL4 T-cell leukemia/lymphoma aGVHD group were injected with donor bone marrow cells (5 × 106/mouse) and plus 500 EL4 cells (5 × 106/mouse).General state,life span and histopathology of the recipient mice and detected chimera were observed.Results The results showed that the mean survival time in radiation group was (10.10 ± 0.43) days,in aGVHD group was(28.12 ± 5.01)days,in EL4 T-cell leukemia/lymphoma aGVHD group was (31.05 ±5.48) days.The mean survival time in aGVHD group and EL4 T-cell leukemia/lymphoma aGVHD group were significantly longer than that in radiation group(all P ＜ 0.01),but there was no significant difference between aGVHD group and EL4 T-cell leukemia/lymphoma aGVHD group (P ＞ 0.05).Histopathological analysis in several target organs (skin,liver and small intestine) confirmed the presence of sever GVHD in aGVHD group and EL4 T-cell leukemia/ lymphoma aGVHD group.Pathological examination showed disorganization of normal tissues and leukemic cell infiltration in EL4 T-cell leukemia/lymphoma aGVHD group.Conclusion The EL4 T-cell leukemia/lymphoma aGVHD mice model is reliable to the experimental research of aGVHD.

Inhibition of endothelial progenitor cells against hepatic vein thrombosis after allogeneic bone marrow transplantation / 中华器官移植杂志

Objective To (e)xplore inhibition of endothelial progenitor cells (EPCs) against hepatic vein thrombosis after allogeneic bone marrow transplantation (BMT).Methods Balb/c mice were randomly divided into three groups: (1) BMT group [Balb/c mice were injected intravenously with 5 × 106 bone marrow cells after total body irradiation (TBI)]; (2) EPCs co-transfusion with bone marrow cells group: 5 × 105 EPCs were infused into recipient mice simultaneously; (3) Normal control group.Liver index was detected on the day 0,5,10,15 and 20 after transplantation.Hepatic vein thrombosis,hepatic cells and vascular endothelial damage were observed under the light microscopy after H&E staining.The injury of liver cells,liver veins,hepatic sinusoidal endothelial cells (SECs)and platelet adhesion conditions were observed under a transmission electron microscope (TEM).The proportion of activated platelets and TNF-α concentration in peripheral blood were detected by using flow cytometry.Results On the day 0,5,10,15 and 20 after transplantation,the proportion of activated platelets,liver index and TNF-α concentrations in BMT group and EPCs co-transfusion group showed an upward trend,peaked on the 15th day,and then decreased.However,they were still significantly higher than those in normal control group (P＜0.05).The above parameters in EPCs co-transfusion group at each time point were significantly lower than those in BMT group (P＜0.05).As compared with BMT group,platelet adhesion decreased,hepatic vein thromboses were reduced,hepatocyte swelling and necrosis were alleviated,and liver damage repaired rapidly in EPCs co-transfusion group.Conclusion EPCs co-transfusion with bone marrow cells could inhibit the hepatic veins thrombosis and ameliorate liver damage significantly.

Recurrent Pneumomediastinum and Subcutaneous Emphysema Complicating Chronic Graft versus Host Disease after Allogeneic Bone Marrow Transplantation

Several noninfectious pulmonary complications can be associated with chronic graft versus host disease (GVHD). Obstructive airway disease can be a clinical feature of chronic GVHD and the histopathology reveals characteristic lesions of bronchiolitis obliterans. Bronchiolitis obliterans is an obstructive pulmonary disorder affecting the small airways, and it was first described as a late complication of allogeneic bone marrow transplantation (BMT). Spontaneous pneumomediastinum and subcutaneous emphysema can occur in the setting of severe bronchiolitis obliterans and only rarely are they the first sign of such disease. We describe here a case of a 27-year old woman who developed recurrent pneumomediastinum and subcutaneous emphysema that were secondary to the bronchiolitis obliterans that complicated chronic GVHD after allogeneic BMT.

Association of Hospital Procedure Volume with Post-Transplant Survival for Allogeneic Bone Marrow Transplantation / 예방의학회지

OBJECTIVE: To examine the association between hospital procedure volume and treatment outcomes following allogeneic bone marrow transplantation (allo-BMT). METHODS: Out of 1, 050 patients who received allo-BMTs between 1998 and 2000 in 21 Korean hospitals, 752 with first allo-BMT and complete data were included in this study. Study subjects were divided into the following three groups according to cumulative hospital experience of all-BMTs during the study period: low ( or =50 cases) volume. Patient outcome was defined as early survival at day 100 and one-year survival. Multiple logistic regression analyses were performed to examine the association between hospital experience and survival at day 100 and one year. RESULTS: When the low volume group was defined as the reference group, the adjusted relative risks (RR) of survival at day 100 for the high volume group were 2.46 (95% CI, 1.13-5.36) for all patients, 2.61 (1.04-6.57) for those with leukemia, and 2.20 (0.47-10.32) for those with aplastic anemia. For one-year survival, adjusted RR for the high volume group were 2.52 (1.40-4.51) for all patients, 1.99 (1.01-3.93) for leukemia, and 6.50 (1.57-26.80) for aplastic anemia. None of the RR for the medium volume group was statistically significant. Patient factors showing significant relationship with survival were donor-recipient relation, human leukocyte antigen matching status, time from diagnosis to transplant, and disease stage. CONCLUSION: The study results suggest that the cumulative experience of hospitals in providing allo-BMT is positively associated with patient survival.

A case of successful allogeneic bone marrow transplantation in a HBV-positive severe aplastic anemia patient with prophylactic lamivudine treatment / 대한내과학회지

Reactivation of hepatitis B virus (HBV) infection has been known to be a serious complication of immunosuppressive or cytotoxic chemotherapy in HBV carriers or chronic hepatitis B patients. We report here a 25-year-old woman who has severe aplastic anemia and chronic hepatitis B underwent successful allogeneic bone marrow transplantation (BMT) with prophylactic lamivudine treatment and showed no evidence of reactivation of hepatitis B, HBV DNA elevation, or liver dysfunction. This result suggests that prophylactic administration of lamivudine to a BMT recipient of chronic hepatitis B might be a safe and promising measure to prevent fatal liver dysfunction.

The Profiles of Plasma Chemokines Following Unrelated Allogeneic Bone Marrow Transplantation and Their Relationship to Transplant-Related Complications

Chemokines are a family of closely related chemotactic cytokines known to be potent attractors for various leukocyte subsets such as neutrophils, monocytes, or lymphocytes. We investigated the chemokine profiles in 26 patients who received unrelated allogeneic bone marrow transplantation (BMT) and evaluated the relationship of chemokines to transplant-related complications. We measured plasma levels of regulated upon activation normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein-1alpha (MIP-1alpha), macrophage inflammatory protein-1beta (MIP-1beta), and interleukin-8 (IL-8) at BMT day -7, day 0, and day 21. When compared with preBMT levels, the mean level of RANTES was significantly decreased at day 21, and the mean level of IL-8 was significantly elevated at day 21. Methotrexate given for graft-versus-host disease (GVHD) prophylaxis and postBMT infectious complication respectively may have contributed to these plasma chemokine level changes. The mean level of IL-8 was significantly higher in patients with infectious complications at day 21 (p=0.009). However, plasma chemokine levels were not associated with the development of acute GVHD and veno-occlusive disease (VOD). Since chemokine production acts in a local manner, plasma levels may not reflect the actual activity of chemokines in target tissue. Further experimental and clinical studies, including chemokine expression in target tissue, are warranted to define the roles of chemokines following allogeneic BMT.

Influence of 1,25-(OH)_2D_3 and salvia miltiorrhiza on T cell subsets and immune status in rats after allogeneic bone marrow transplantation / 第三军医大学学报

Objective To investigate the effect of 1,25-(OH)2D3 and salvia miltiorrhiza on T cell subsets and cytokines in rats after allogeneic bone marrow transplantation.Methods Female Wistar rats were used as recipients and male SD rats were used as donors.All Wistar rats were divided into aGVHD group and intervention groups at random,and the intervention groups were further divided into 1,25-(OH)2D3 group,salvia miltiorrhiza group and combination group.The changes of T cell subsets (CD4+ and CD8+) and cytokine (IL-2,IFN-?,IL-4 and IL-10) in every group were detected and measured.Results When the presentation of aGVHD was relatively conspicuous,CD4+ and CD8+ were increased,and the increase of CD4+ was predominant.Compared with the difference prior to transplantation,the difference was statistically significant (P

Effect of Donor Lymphocyte Infusion for a Patient with Isolated Knee Joint Relapse of Acute Lymphoblastic Leukemia after Allogeneic Bone Marrow Transplantation / 대한혈액학회지

Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) after allogeneic bone marrow transplantation (BMT) in the absence of marrow involvement is a rare event, and the mechanisms underlying the selective involvement of extramedullary sites remain undefined. These might be due to relapse in sanctuary sites where the leukemic cells are resistant to preparative regimen, or a stronger graft-versus-leukemia effect in the marrow as compared with peripheral tissues. We report an adult ALL patient who experienced isolated extramedullary relapse in the right pretibial soft tissue and knee joint 42 months after allogeneic BMT. He was treated with localized radiotherapy followed by systemic chemotherapy and donor lymphocyte infusion. After treatment, he is currently well with no evidence of leukemia recurrence for 12 months.

The Effects of Multiple Transfusion on the Outcomes of Bone Marrow Transplantation from HLA-matched Sibling Donor in Patients with Severe Aplastic Anemia / 대한소아혈액종양학회지

PURPOSE: We investigated the effects of pretransplant-transfusion on engraftment, graft versus host disease (GVHD) and graft rejection after bone marrow transplantation (BMT) in children with severe aplastic anemia who had HLA-identical sibling donor. METHODS: We reviewed retrospectively the medical records of 47 children with severe aplastic anemia who received grafts from HLA-matched sibling donor using same conditioning regimen (procarbazine, antithymocyte globulin, and cyclophosphamide) from September 1986 to May 2001. GVHD prophylaxis consisted of cyclosporine and short-term methotrexate. Patients receiving multiple transfusion more than 40 transfused units in total before BMT were defined as high-risk group (HRG) and those with less than 40 transfused units were as standard-risk group (SRG). RESULTS: Among 47 patients, 30 patients were classified into SRG and remaining 17 were into HRG. The median time from diagnosis to transplant was 4 (range, 1~14) months in SRG and 36 (range, 3~360) months in HRG. Primary engraftment was achieved in all patients. Acute GVHD (> or =grade II) in HRG (13.3%) was comparable with in SRG (5.9%) (P=0.221), meanwhile corresponding fugures for chronic GVHD was 1 (3.3%) and 2 (11.8%). All of these patients have experienced complete resolution of GVHD and are no longer receiving immunosuppressive therapy. Booster stem cell infusion was needed for poor graft function (n=3) in SRG and also for poor graft function (n=1) or progressive rejection (n=3) in HRG. Five-year disease free survival rate was 100% in SRG and 94.1 6% in HRG (P=0.18). CONCLUSION: These findings suggest that multiple transfusion may be not a risk factor for rejection or poor outcome. Progressive rejection was observed only in patients with multiple transfusion but did not affect the survival.

Influence of Karyotype on Outcome of Allogeneic Bone Marrow Transplantation for Adults with Precursor B-Lineage Acute Lymphoblastic Leukemia in First or Second Remission / 대한혈액학회지

BACKGROUND: The discrepancy of therapeutic outcome between pediatric and adult patients with acute lymphoblastic leukemia (ALL) can be attributed in part to the higher frequency of adverse genetic abnormalities in adults. Several features such as age, leukocyte count, karyotype, and the rapidity of leukemic cell clearance have been noted to influence outcome of adult ALL in chemotherapy setting. However, the prognostic relevance of these factors has not been definitely evaluated in allogeneic BMT setting. METHODS: A total of 41 consecutive adults with precursor B-lineage ALL who had a successful karyotype and treated with allogeneic BMT while in first or second complete remission (CR) were entered onto the study. Cases known to be t(9;22) or t(4;11) were classified as unfavorable karyotype. RESULTS: There were 21 males and 20 females with median age 27 (range, 15~43) years. The distribution of FAB types was as follows : L1 26 cases (63.4%), L2 15 cases (36.6 %). Unfavorable karyotypes were identified in 12 patients (29.3%). Disease status at the time of transplant was first CR (n=37) or second CR (n=4). With a median follow-up of 26 months (range, 7~65 months), the probability of disease-free survival (DFS) was 66.5% and 49.9% at 2 and 5 years, respectively. In univariate analyses, characteristics predicting for worse DFS were FAB type (L2), pretransplant status (second CR) and unfavorable karyotype. Further multivariate analysis showed that the most powerful predictive factor for DFS was karyotype (P<0.01). CONCLUSION: Our clinical data shows that karyotype is the most important prognostic factor in adult precursor B-ALL after allogeneic BMT.

A Case of Allogeneic BMT in a Patient with Severe Combined Immune Deficiency / 대한소아혈액종양학회지

A 11-month-old male with severe combined immune deficiency (SCID) received allogeneic bone marrow transplantation (BMT). He had suffered from recurrent infection and chronic diarrhea. Two older brother died of pneumonia 2 months after birth, but his HLA identical sister was healthy. He had very low number of T lymphocyte and NK cell. Although number of B lymphocyte was normal, level of immunoglobulin was extremely low. First BMT was done when he was 11 months old. Eighteen milliliter of bone marrow was simply infused without conditioning or GVHD prophylaxis. T lymphocyte appeared and fever which persisted despite use of antibiotics disappeared at day 7. Grade II GVHD developed, but was well controlled with corticosteroid. T lymphocyte subpopulation became normal at day 42. But pancytopenia developed and persisted despite use of G-CSF. Second BMT was done 4 months after 1st BMT. The conditioning regimen included busulfan (8 mg/kg) and cyclophosphamide (200 mg/kg), and ATG, cyclosporine and short-course MTX were used for GVHD prophylaxis. He achieved ANC> 500/uL at day 20 and platelet> 20,000/uL at day 29. BM examination on day 45 showed that 100% of marrow cells were donor origin. Acute and chronic GVHD did not develop. Since T lymphocyte was observed on day 21, various immunological parameters were normalized sooner or later. Immunological reconstitution was complete on day 280. Vaccination was given after 1 year of BMT and he is healthy now.

Effects of Mixed Chimerism and Immune Modulation on GVHD, Disease Recurrence and Survival after HLA-identical Marrow Transplantation for Hematologic Malignancies

BACKGROUND: The success of allogeneic bone marrow transplantation(allo-BMT) is affected by underlying disease relapse. Although mixed chimerism(MC) is not necessarily a poor prognostic factor, several groups have suggested that MC is associated with an increased risk of disease relapse. There is evidence that patients with MC benefit from additional immunotherapy if the treatment is started in minimal residual disease status(mixed chimerism status), not in frank hematological relapse. The purposes of this study are to evaluate 1) the risk for relapse or graft rejection in correlation to persistent MC status after allo-BMT, and 2) the possibility of preventing relapse by immune modulation treatments (withdrawal or rapid taper-off of post-transplant immuno-suppression, additional interferon treatment, or the administration of donor lymphocytes) in hematologic malignancies. PATIENTS AND METHODS: Of 337 allogeneic donor-recipient pairs between March 1996 and August 1998, 12 patients who showed persistent or progressive MC and who received immune modulation treatments were evaluated. Twelve patients, median age 31 years(range 9 to 39 years), received an allo-BMT for: acute myelogenous leukemia(AML, n = 5), chronic myelogenous leukemia(CML, n = 4), acute lymphocytic leukemia(ALL, n = 3). Serial polymerase chain reaction(PCR) analysis of YNZ 22-, 33.6-minisatellites or Y chromosome-specific PCR analysis at short term intervals(pre- and post-transplant 1, 3, 6, 9, ... months) was performed. Once MC was detected, immune modulation treatments on the basis of increasing MC in an early phase of recurrence of underlying disease were started. RESULTS: Nine of 12 patients converted to complete chimerism(CC) (AML 5/5, CML 3/4, ALL 1/3). Four of 9 CC patients developed graft-versus-host disease(GVHD) grade < or = 2 during immune modulation. All were treated successfully with steroids. Three patients who were not converted to CC showed relapse of underlying diseases or graft failure. CONCLUSION: The results demonstrate that, in patients with hematologic malignancies after allo-BMT, persistent MC is associated with relapse of underlying diseases or graft failure. Furthermore, when patients receive early immune modulation treatment, MC can be changed to complete donor pattern chimerism and ultimately prevent relapse.

Donor Leukocyte Infusion as Treatment for Relapsed Leukemia after Allogeneic Bone Marrow Transplantation : Graft-versus-Leukemia Effect / 대한혈액학회지

BACKGROUND: Donor leukocyte infusion (DLI) is an effective therapy for patients who relapse with leukemia after allogeneic bone marrow transplantation (BMT). This is due to the fact that the immune reactivity of infused allogeneic lymphocytes on relapsed leukemia cells plays a major role in the control of leukemia. However, severe graft-versus-host disease (GVHD) and pancytopenia compromise the success of this treatment in a substantial number of patients. METHODS: To evaluate the effect of DLI, we surveyed 6 BMT centers regarding their use of DLI for relapsed leukemia after BMT. Detailed forms were used to gather data regarding the original BMT, relapse, response to DLI, complication and survival. Reports of 11 patients were consequently available for analysis. RESULTS: Five (83.3%) of 6 patients with chronic myeloid leukemia (CML) achieved complete remission (CR) [time-to-CR; 116 (27~180) days after DLI], and currently 4 are alive in CR (49~436 days). Five patients (83.3%) developed GVHD, and 2 developed pancytopenia which was related to DLI. In acute leukemia, all patients received salvage chemotherapy prior to DLI. Only 1 of 3 patients with acute lymphoblastic leukemia (ALL) who had early relapse achieved CR, but durable remission was not yet confirmed (62+ days). Both 2 patients with acute myeloid leukemia (AML) achieved CR, and their CR durations were 242+ and 326 days after DLI, respectively. CONCLUSION: This study demonstrates that DLI can exert considerable effects against myeloid forms of leukemia, especially in CML. Further investigations of separating GVHD from the graft- versus-leukemia effect and finding more effective anti-leukemia approaches on acute leukemiaare necessary to improve the current DLI limitations.

Allogeneic Bone Marrow Transplantation for Myelodysplastic Syndromes / 대한혈액학회지

BACKGROUND: The myelodysplastic syndromes (MDS) can be categorized as a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Although the natural history of MDS varies, traditional treatments are not curative and allogeneic marrow transplantation offers potentially curative treatment for MDS. METHODS: In our center, 10 patients underwent allogeneic bone marrow transplantation (BMT) between December 1989 and May 1997. The minimum follow-up of 3 months was possible in 10 patients, for whom treatment-related complications and clinical outcomes were assessed. RESULTS: The median age of the 10 patients was 33 (range 20~40) years. The median time from diagnosis to BMT was 34 (3~116) months. By morphology, 5 patients had advanced MDS (i.e., RAEB, RAEB-t, CMML) and 5 patients had less advanced MDS (RA). By Bournemouth score, 8 patients had a score 2~3 and two patients had a score 4. By IPSS, 5 patients were in intermediate-1 group, 3 patients in intermediate-2 group and 2 patients in high risk group. Patients were prepared for transplant with either a total body irradiation (TBI)+cyclophosphamide (n=7), busulfan+TBI (n=2) and busulfan+cyclophophamide (n=1). All patients received CsA+short course MTX for GVHD prophylaxis. Successful engraftment was confirmed in all patients. The overall incidence of acute GVHD was noted in 70% (7/10 patients) and grade IV acute GVHD developed in 2 patients (20%). Five patients were evaluable for the development of chronic GVHD and 2 patients (40%) developed limited chronic GVHD. The duration of median follow-up was 8.1 months. At present five patients are alive and disease-free 3 to 21 months (median survival duration : 8.2 months) post-transplantation resulting in a 2-year disease-free survival of 44%. 2-year disease free survival was 63% in less advanced MDS and 25% in advanced MDS. CONCLUSION: Allogeneic BMT should be considered when any clinical evidence of disease progression to a more advanced stage becomes apparent. International prognostic scoring system (IPSS) and Bournemouth score can also be used to gauge timing for BMT. For patients were in intermediate-1 or intermediate-2 group by IPSS, BMT can be justified if the patient is young and has an HLA matched sibling donor.

Allogeneic Bone Marrow Transplantation Experience for Children with Severe Aplastic Anemia and Refractory Leukemia

PURPOSE: We reviewed the result of allogeneic bone marrow transplantation(BMT) from HLA-identical sibling donors in children with refractory stem cell disorder along with future implication. METHODS: Forty-two children with refractory stem cell disorder received BMT from HLA-identical sibling donors between Nov. 1983 and Feb. 1995. Out of 42 children, 23 cases were severe aplastic anemia(SAA) and 19 cases were refractory leukemias. There were 20 male and 22 female with median age of 13 years (range, 2-17) and median follow-up of 36 months (range, 4-139 months). RESULTS: 1) The overall survival rate of all patients was 73.8%. The survival rate for SAA cases was 87.0%, while that for leukemia was 57.9%. 2) Acute GVHD(> or = grade II) was observed in 16.7% of all patients, 8.7% of SAA patients and 26.3% of leukemia patients, respectively. Chronic GVHD developed in 9.5% of all patients, 4.8% of limited type and 4.8% of extended type. No death was directly attributable to GVHD. 3) The causes of death after allogeneic BMT were graft rejection(7.1%), relapse of leukemia(7.1%), thrombotic thrombocytopenic purpura(4.8%), veno-occlusive disease, sepsis and CMV pneumonia respectively 2.4%. 4) The most common complication except death after allogeneic BMT was herpes zoster(26.2%). The other complications were hemorrhagic cystitis(7.1%), bronchiolitis obliterans and measles respectively 2.4%. CONCLUSIONS: We confirmed that allogeneic BMT is the curable treatment for children with refractory stem cell disorder. The most important factors that influence the result of transplantation are interval between diagnosis and transplantation in severe aplastic anemia and remission state at transplantation in leukemia.

Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia / 대한치료방사선과학회지

Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6fractions/3days (6 patients) or 1320 cGy/8 fractions/4days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

A Clinical Evaluation of Ocular Manifestation in Bone Marrow Transplanted Patients

During the last decade, allogeneic bone marrow transplantation(BMT) has become the treatment of choice in severe aplastic anemia and many types of leukemia. However, there are several complications such as Graft-vs-Host Disease(GVHD), infection, Host-vs-Graft Reaction(HVGR). One of the most serious late complications of BMT is GVHD. This immunological reaction is reportedly caused by donor T lymphocytes reacting against incompatible minor transplantation antigens in host tissue. The clinical manifestation of GVHD involves the skin, gastrointestinal tract, liver and mucosal membranes in the mouth and eyes. One of the most frequent ocular complication after BMT is the "dry eye syndrome" which involves conjunctiva, cornea and the lacrimal glands. The "dry eye" is characterized by subjective symptoms such as pain, foreign body sensation and decreased vision. The epithelial degeneration, due to reduced tear production and alteration in the tear film, creates dry spots and increased mucus strands and debris. We present an analysis of ocular manifestation of 27 out of 81 bone marrow transplanted patients for hematologic malignancies(HM) and severe aplastic anemia(SAA) from March 1983 to January, 1990 at St. Mary's Hospital. The results were as follows: 1) 16 out of 27(59%) BMT patients developed GVHD and 14 out of 27(52%) BMT patients developed dry eyes; 2) 11 out of 16(68%) patients with GVHD developed dry eyes; whereas, 3 out of 11(27%) patients without GVHD developed dry eyes(P<0.05); 3) Four out of 10(40%) patients with a GVHD developed dry eys, whereas 7 out of 11(64%) patients with cGVHD developed dry eyes.