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Biomedical subjects

W S Min

Publications and source records attributed to W S Min.

32 records · Page 2Linked to original sources
PubMed2000

Additional stem cell therapy for graft failure after allogeneic bone marrow transplantation.

In this study we retrospectively evaluated the effect and outcome of a boost dose of donor stem cells without additional chemotherapy or total body irradiation. Between March 1983 and August 1999, 20 of 788 (2.5%) patients receiving allogeneic bone marrow transplantation (BMT) were treated with an additional boost dose of donor cells. The reasons for the use of the boost treatment were primary graft failure (early rejection; n = 7), secondary graft failure including late rejection (n = 10), refractory pure red cell aplasia caused by the remaining recipient cells producing anti-erythrocyte antibodies (n = 2), and donor lymphocyte infusion induced pancytopenia (n = 1). The patients were aged from 17 to 48 years (median age 31 years). The underlying diseases of the patients were severe aplastic anemia in 12 patients, acute myelogenous leukemia in 3, acute lymphocytic leukemia in 3, and chronic myelogenous leukemia in 2. The donors were human leukocyte antigen-identical siblings in 18 cases, 1 mismatched related donor, and 1 unrelated donor. The cell source was bone marrow in 6 cases and peripheral blood progenitor cells in 14. The median interval between BMT and the boost treatment was 7 weeks (range 1-124). No conditioning regimen was given prior to the boost treatment for 11 patients, while 4 received total nodal irradiation (TNI) plus antithymocyte globulin (ATG), 3 ATG alone, and 2 TNI plus steroid. The median infused booster mononuclear cell dose was 2.55 x 10(8)/kg (range 0.28-37.0). Fifteen (75%) patients achieved a hematological recovery. After the boost treatment, 6 of 20 (30%) patients developed acute graft-versus-host disease (GVHD) > or = grade II, 3 of whom had had prior GVHD. Five (31.3%) of the evaluable 16 patients developed chronic GVHD. The GVHDs were easily controlled using immunosuppressive agents except in the case of 1 patient. Five patients died after the boost treatment; 2 within 30 days, 2 within 60 days, and 1 after 32 months. The causes of death were: 3 engraftment failures, 1 late rejection, and 1 infection following GVHD. With a median follow-up of 31.5 months (range 6-92), the Kaplan-Meier method estimated that the overall survival rate 1 and 3 years after the boost treatment was 80 and 71%, respectively. The survival of patients with primary graft failure was determined to be significantly lower compared to that of patients with secondary graft failure, using the log rank test (p = 0.0176). Disease category, stem cell source, conditioning prior to a boost treatment, and year of boost treatment did not have an influence on survival. We conclude that the reinfusion of donor stem cells is frequently successful in achieving engraftment with rare occurrence of fatal GVHD. Furthermore, relatively good long-term survival was demonstrated.

Actuarial Analysis↗
PubMed2000

Topotecan-based combination chemotherapy in patients with transformed chronic myelogenous leukemia and advanced myelodysplastic syndrome.

BACKGROUND: Patients with transformed chronic myelogenous leukemia(CML) and advanced myelodysplastic syndrome(MDS) have poor prognosis. The aim of this study is to evaluate the feasibility of second chronic phase induction in accelerated phase(CML-AP) or blastic crisis of CML(CML-BC) and remission induction in advanced MDS by combining topoisomerase I inhibitor (topotecan) with topoisomerase II inhibitor(mitoxantrone). METHODS: Twenty-four evaluable patients were entered on this study with a median age of 34 years. Eighteen patients with transformed CML(7 CML-AP, 11 CML-BC) and 6 patients with advanced MDS were treated. Topotecan was administered as 1.5 mg/m2/day by continuous infusion over 24 hours daily for 5 days every 4 to 8 weeks until remission. To enhance the tumoricidal effects, mitoxantrone(12 mg/m2/day, Days 1-3) was added. RESULTS: Eight patients(33%) achieved a complete remission(CR). Four of 7 patients with CML-AP(57%), 2 of 4 patients with CML-lymphoid blastic crisis (-LBC)(50%) and 2 of 6 patients with advanced MDS(33%) had CR lasting more than 45 days(45 to 400 days). There was no CR in the patients with CML-myeloid blastic crisis(-MBC). The dose level of 1.5 mg/m2/day(7.5 mg/m2/course) of topotecan was well tolerated in all patients. Mucositis occurred in 69% of patients (severe in 5%) and diarrhea in 67%(severe in 8%). In addition, there were no new or unexpected toxicities in the patients who were treated at this dose(7.5 mg/m2/course). In patients who recovered their neutrophil count, the absolute neutrophil count(ANC) remained below 500/microL for a period of 13 to 58 days(median 21 days) and the time to ANC recovery was associated with pretreatment severity of bone marrow fibrosis(mainly CML patients). Likewise, in the patients who recovered unsupported platelets, the platelets remained below 20,000/microL for a period of 0 to 37 days (median 19 days). CONCLUSION: The combination of topotecan-mitoxantrone has shown modest activity in CML-AP, CML-LBC and advanced MDS with acceptable toxicities.

Adult↗
PubMed2000

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.

Adolescent↗
PubMed2000

Necrotizing enterocolitis: experience of 27 cases from a single Korean institution.

Necrotizing enterocolitis (NEC) can involve any site in the gastrointestinal tract and is a fatal complication of immunosuppression. To characterize NEC, clinical and radiological characteristics were analyzed. A total of 27 cases of NEC were identified from January 1993 to August 1998, and medical records were reviewed. NEC was diagnosed by clinical and radiological criteria, and other mimicking conditions were excluded. Of the NEC cases, 22 (81.5%) occurred in patients with underlying hematologic malignancy. All patients complained of abdominal pain and fever at the time of inclusion. Escherichia coli was the most common pathogen identified. The most common finding by computed tomography was single-layered diffuse bowel wall thickening with variable density. Other findings were ascites, fascial thickening, pneumatosis, and mesenteric lymphadenopathy. Of the patients, 25 were treated with antimicrobials with or without recombinant hematopoietic growth factors, and 2 were treated with surgery because of perforation and profound bleeding. Among the 12 patients who died, NEC was the direct cause of death in 7 patients. In conclusion, computed tomography is an effective tool for early diagnosis of NEC. Bowel rest, broad-spectrum antimicrobials, and recombinant hematopoietic growth factors are important aspects of treatment. Surgery should be reserved for complicated cases.

Adolescent↗
PubMed1997

Esophageal aspergillosis after bone marrow transplant.

The prolonged immune suppression associated with bone marrow transplants predisposes to fungal infections including Aspergillus. Disseminated aspergillosis occurs in up to 60% of patients with invasive pulmonary aspergillosis; sites of involvement include the brain, gastrointestinal tract, kidney, liver, thyroid, heart, and spleen. There is only one report of isolated esophageal aspergillosis. A recent acute myelogenous leukemia patient had isolated esophageal aspergillosis after bone marrow transplantation which was successfully treated with amphotericin B.

Adult↗
PubMed1997

Pre-emptive ganciclovir treatment can play a role in restoration of hematopoiesis after allogeneic bone marrow transplantation.

We performed pre-emptive ganciclovir therapy on two allogeneic bone marrow transplant (BMT) recipients with myelosuppression associated with cytomegalovirus (CMV) antigenemia after successful engraftment. During the hypoplastic phase, the nucleated cells in the bone marrow and peripheral blood were revealed to be of donor origin by DNA fingerprinting. These two patients had CMV antigen in their peripheral leukocytes. Following the pre-emptive ganciclovir treatment, both of them showed gradual recovery of granulocytes and platelets. They are still alive with stable bone marrow function. From these results, we suppose that infection or reactivation of CMV can suppress bone marrow function after bone marrow transplantation, and the pre-emptive ganciclovir therapy based on the CMV antigenemia may be beneficial if bone marrow function deteriorates after engraftment.

Adolescent↗
PubMed1995

Immune suppression therapy in aplastic anemia: influencing factors on response and survival.

OBJECTIVES: Immune suppression (IS) therapy has provided another opportunity of cure or improvement in the aplastic anemia patients who cannot receive bone marrow transplantation due to many causes. There are a few reports regarding the factors that affect response, survival and prognosis after IS therapy, including antilymphocyte globulin (ALG) in aplastic anemia. Therefore, we analysed our experience to determine the prognostic factors. METHODS: Statistically analysed were 172 patients, from April 1982 to July 1992, who were diagnosed as severe aplastic anemia and treated with IS therapy, including ALG, at Catholic University Medical College, St. Mary's Hospital. RESULTS: Among 172 severe aplastic anemia (SAA) patients who entered the study from April 1982 to July 1992, 144 patients were analysed for response and 122 patient for survival. 58.4% (84/144) responded after the first course of IS therapy. Among those who did not respond on the first course an additional 44% (11/25) responded after the second course of IS therapy. Prognostic factors that might affect the response to the treatment and survival were analysed. In a univariate analysis of patients with no previous history of treatment before is therapy, and a shorter interval between diagnosis and treatment, higher hemoglobin levels before IS therapy, and higher granulocyte counts and combined use use of cyclosporin A(CSA) were positively associated with response (p < 0.05). The combined use of CSA during IS therapy, younger age, lower monthly requirement of platelets transfusion before IS therapy, higher leukocyte counts, higher percent of polymorphonuclear leukocytes, lower percent of lymphocyte, higher bone marrow cellularity and response were positively associated with survival (p < 0.05). In a multivariate analysis, shorter interval between diagnosis and treatment, no combined use of hemopoietic stimulants, such as androgen, and lesser total amount of transfusion were positively associated with Response (p < 0.05). Higher leukocyte counts before IS therapy and the combined use of CSA during IS therapy were significantly associated with longer survival (p < 0.05). Patients with complete or partial response had excellent prognosis (96.7%-100% of 5 year survival rates). In contrast, patients with no response after IS therapy had 45.1% of 5 year survival rates. CONCLUSIONS: With these results from the retrospective study of IS therapy, we find many valuable factors that have an influence on response or survival. IS therapy improves the survival of responded patients with SAA, and we confirmed that IS therapy is an important therapeutic tool for the SAA patients who are not feasible candidates for bone marrow transplantation.

Adolescent↗
PubMed1994

Allogeneic bone marrow transplantation in Korea: 1983-92.

Between March 1983 and December 1992, we performed 178 allogeneic BMTs for patients with hematopoietic stem cell disorders: 48 acute myelogenous leukemia (AML), 27 acute lymphoblastic leukemia (ALL), 40 chronic myelogenous leukemia (CML), 55 severe aplastic anemia (SAA), 6 myelodysplastic syndrome (MDS), 1 non-Hodgkin's lymphoma and 1 hybrid leukemia. Twenty-five of 48 AML are in disease-free survival (DFS). Fifteen of 27 ALL are in unmaintained remission. Twenty-four of 40 CML are in DFS. Forty-four out of 55 SAA patients are alive and well. Comparing the survival between standard (< or = CR1: 21 of 31 (68%)) and high risk (> or = CR2: 4 of 17 (24%)) AML, our data suggest that the preparative regimen for high risk AML was not potent enough to eradicate the residual disease in advanced AML. Although our cases are limited and the follow-up period is short, the result of ALL (overall: 56%, standard risk (adult < or = CR1, children < or = CR2: 10 of 14 (71%) and high risk (adult > or = CR2, children > CR2): 5 of 13 (38%)) and CML (overall: 60%; CP: 19 of 27 (70%), AP or BC: 5 of 13 (38%)) are promising. The probability of 5 year survival of SAA was 80 +/- 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Radiation and heat sensitivity of human T-lineage acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) clones displaying multiple drug resistance (MDR).

The hyperthermia as well as radiation responses of multidrug resistant (CEM/VLB100 with classical MDR and CEM/VM-1 with atypical MDR), methotrexate resistant (CEM/MTX) subclones of CCRF-CEM T-lineage ALL cell line were compared with those of a drug sensitive (CEM-1-3) subclone from the same parent cell line. Also analyzed were the hyperthermia as well as radiation responses of multidrug resistant (HL60/AR) and drug sensitive subclones of the HL60 AML cell line. Notably, the drug resistant subclones of CEM and HL60 were as sensitive to hyperthermia as were the drug sensitive subclones. Importantly, no thermotolerant plateau was observed in the hyperthermia survival curves of the drug resistant subclones, indicating that drug/multidrug resistance is not associated with a greater likelihood of thermal tolerance development during hyperthermia. Similarly, the drug resistant CEM and HL60 subclones were not more radiation resistant than the drug sensitive subclones. Thus, the classical or atypical forms of multidrug resistance or methotrexate resistance of the analyzed leukemic cell lines were not associated with radiation resistance. Furthermore, the radiation survival curves of the drug resistant subclones lacked a distinct initial shoulder and their n values were not greater than those of the drug sensitive subclones, suggesting that multidrug resistance is not associated with an increased ability to repair or accumulate sublethal radiation damage. Our findings provide evidence that there is no apparent association between drug/multidrug resistance and heat or radiation sensitivity of CEM T-lineage ALL or HL60 AML leukemia cells. The results of this study indicate that acquired resistance to methotrexate, vinblastine, vincristine, etoposide, actinomycin-D, adriamycin, or daunomycin, or pleiotropic multidrug resistance do not necessarily confer radiation resistance for human leukemic cells.

Adaptation, Physiological↗
PubMed1991

Radiation sensitivity of human B-lineage lymphoid precursor cells.

We studied the radiation sensitivity of eight immunophenotypically distinct B-lineage lymphoid precursor cell (LPC) lines of acute lymphoblastic leukemia (ALL) or fetal liver origin corresponding to discrete developmental stages of human B-cell ontogeny. The radiation sensitivity of B-lineage LPC showed a temporal association with the distinct stages of development. FL112 and FL114 fetal liver pro-B cells (Stage 0 B-lineage LPC) with germline immunoglobulin heavy chain (IgH) genes but rearranged T-cell receptor gamma (T gamma) genes (DO of FL112 = 80.3 cGy, DO of FL114 = 50.2 cGy), REH ALL pre-pre-B cells (Stage I B-lineage LPC) with rearranged IgH and T gamma genes (DO = 66.1 cGy), and NALM-6 ALL pre-pre-B/pre-B cells (Stage II B-lineage LPC) (DO = 50.5 cGy) corresponding to the earliest three stages of human B-lymphocyte development were the most radiation sensitive B-lineage LPC populations. By comparison, KM-3 ALL pre-B (Stage III B-lineage LPC) (DO = 194.7 cGy), HPB-NULL ALL pre-B (Stage IV B-lineage LPC) (DO = 134.6 cGy), and sIgM+ RAJI/NAMALWA early B (Stage Va/b B-lineage LPC) cell lines (DO of RAJI = 144.0 cGy, DO of NAMALWA = 165.5 cGy) corresponding to the later stages of human B-lymphocyte development were much more radiation resistant. These results indicate that the radiation sensitivity of B-lineage LPC decreases during maturation within the B-lineage lymphoid precursor pathway. By comparison, the S-phase index (% of S-phase cells as determined by DNA flow cytometry) or proliferation index (% S + G2M), cellular protein content, intracellular glutathione (GSH) level, glutathione-S-transferase (GST) activity, intracellular pH, or free cytoplasmic calcium concentration did not correlate with the radiation sensitivity of the B-lineage LPC.

B-Lymphocytes↗
PubMed1990

Thermal sensitivity and thermal tolerance of human B-lineage acute lymphoblastic leukemia (ALL) cells.

The thermal sensitivities of four B-cell precursor acute lymphoblastic (ALL) cell lines (REH and KM-3 = pre pre B-ALL; NALM-6 and HPB-NULL = pre B-ALL), and 1 B-cell ALL (NAMALWA) cell line were studied and compared to the thermal sensitivity of the T-lineage ALL cell line MOLT-3 using an in vitro clonogenic assay system by limiting dilution. B-lineage ALL cells were as sensitive to hyperthermia as were T-lineage ALL cells. D0 values at 42 degrees C ranged from 44.9 min (NALM-6) to 85.6 min (NAMALWA), D0 values at 43 degrees C ranged from 15.3 min (NALM-6) to 35.7 min (KM-3), and D0 values at 44 degrees C ranged from 11.1 min (NALM-6) to 23.8 min (HPB-NULL). By comparison, the D0 values of MOLT-3 cells were 95.1 min at 42 degrees C, 23.8 min at 43 degrees C, and 14.7 min at 44 degrees C. The maximum log kill values which were observed ranged from 0.8 log (KM-3 and HPB-NULL) to 1.3 logs (NALM-6) at 42 degrees C, from 1.4 logs (KM-3) to 4.2 logs (NALM-6) at 43 degrees C, and from 3.8 logs (HPB-NULL) to 4.8 logs (NALM-6) at 44 degrees C. A thermal tolerant plateau was observed in the hyperthermia survival curves of REH, NALM-6, and HPB-NULL cells, providing circumstantial evidence that thermal tolerance may develop in some B-cell precursor ALL cells after 90-120 min of continuous heating. In contrast, no thermal tolerant plateau was observed in the hyperthermia survival curves of pre-pre-B-ALL/KM-3 B-cell ALL/NAMALWA or T-lineage ALL/MOLT-3 cells. The kinetics of development and decay of thermotolerance was studied for NALM-6 cells. Thermotolerance after a priming heat exposure to 42 degrees C for 30 min was maximum at 8 hr with a maximum thermotolerance ratio of 2.0, and it decayed by 24 hr. These findings extend previous studies on the thermal sensitivity of human leukemia cells and provide new information on the thermal sensitivity and thermotolerance of B-lineage ALL cells.

B-Lymphocytes↗