BACKGROUND: Classically bone marrow (BM) is the major source of hematopoietic stem cells for the transplantation. Recently, hematopoietic stem cells circulating in peripheral nlood and umbilical cord stem cells have been widely accepted for use in high dose chmotherapy requiring hematopoietic stem cells support. Number if CFU-GM and CD34+ cells are routinely used to assess the engraftment potential of BM aspirates and leukapheresis harvests. However, these parameters predominantly reflect clonogenic cell activity which might only be relevant to short-term hematopoeitic reconstitution, and not necessarily reflect the hematopoeitic stem cell activity capable of sustained engraftment. Long-term culture system is regarded as a quantitative method of estimating hematopoietic stem cell activity in clinical samples. METHODS: We enumerated CFU-GM and CD34+ cells in G-CSF mobilized peripheral blood (MPB), BM and umbilical cord blood (UCB). We obtained the number of LTC-IC from each of these hematopoietic stem cell sources using the long-term culture system. These parameters have compared between the stem cell sources. RESULTS: CD34+ cells were detected in MPB, BM, and UCB at incidences of 2.27+/-1.58%, 0.74+/-0.55%, 1.24+/-0.24% of total mononuclear cells. The highest number of CD34+ cells were seen in UCB. The colony counts higher in UCB than in MPB and BM. Direct comparison of LTC-IC was made between three sources based on CD34+ cell counts. The total numbers of LTC-IC per 105 CD34+ cell were 713 for UCB, 263 for BM, 104 for MPB. These UCB was superior to BM and MPB by cell all three parameters; CFU-GM, CD34+, LTC-IC. CONCLUSION: We speculate that UCB should be better source of hematopoietic stem cell transplantation as well as gene therapy if it could be expanded.
Bone Marrow* ; Cell Count ; Fetal Blood* ; Genetic Therapy ; Granulocyte Colony-Stimulating Factor ; Granulocyte-Macrophage Progenitor Cells ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Incidence ; Leukapheresis ; Stem Cells* ; Umbilical Cord*

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.
Anemia, Refractory, with Excess of Blasts ; Bone Marrow Transplantation* ; Bone Marrow* ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Follow-Up Studies ; Hematopoiesis ; Humans ; Incidence ; Myelodysplastic Syndromes* ; Natural History ; Siblings ; Tissue Donors ; Whole-Body Irradiation

No abstract available.
Humans ; Idarubicin* ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute*

BACKGROUND: We assessed the toxicity and feasibility of the three-alkylator combinations as conditioning regimens for allogeneic hemopoietic stem cell transplantation (HSCT) in 23 adult patients with acute leukemia. METHODS: Sixteen patients were transplanted for acute myeloid leukemia, six for acute lymphoblastic leukemia, and one for myelodysplastic syndrome. Group A included thirteen cases of relapsed refractory, 2 relapsed after first HSCT and group B eight patients in first complete remission or two in second complete remission. Eleven cases received G-CSF mobilized CD34+allogeneic peripheral blood stem cells (PBSCs) in addition to bone marrow (BM) and three in vivo expanded BM by G-CSF and eight unmanipulated BM and one from syngeneic BM after conditioned with busulfan, thiotepa and melphalan (n=14) or cyclophosphamide, thiotepa and melphalan (n=6) or TBI, melphalan and thiotepa (n=3). RESULTS: Twelve of thirteen patients in group A patients engrafted successfully and only one patient failed to achieve complete remission (CR). All patients in group B had successful engraftment. The median days reaching absolute neutrophil count (ANC) more than 500/microliter and platelet more than 30,000/microliter in group A and group B were 13.4 days (7-22), 17.9 days (9-40) and 16.3 days (10-21), 22.6 days (13-38), respectively. Acute graft vs host disease (GVHD) developed in both groups with the incidence of seven (78%) for group A and six (60%) for group B. The major regimen-related toxicity was mucositis with incidence of 95.7% (22/23). The disease free survival rate after HSCT with median follow-up of 161 days (31-283 days) and 101 days (22-163 days) in each group were 24% and 62.5%, respectively. CONCLUSION: Although the observation period is limited, this study shows that the combination of triple-alkylating regimens are tolerable as a preparative regimen for allogeneic HSCT for both high-risk and standard-risk leukemic patients. We need to confirm effects of these regimens in prospective randomized-controlled studies in the future. (allo-BMSCT) and 14 cases of autologous peripheral blood stem cell transplantation (aPBSCT) were underwent. With a median follow-up of 293 days (range, 35~510), the relapse rate was 34.1% (14/41 cases) in chemotherapy-only group and 13.5% (5/37 cases) in transplant-group. The probability of disease-free survival (DFS) at 2 years of chemotherapy-only group, aPBSCT group, and allo-BMSCT group were 20.1%, 44.9%, and 90%, respectively. The relapse-probability at 2 years of three groups were 76.1%, 55.1% and 11.1% in order, respectively. Univariate analyses showed that age (P=0.0274) and augmentation with BHAC (p=0.0334) were significant factors for achieving CR.
Adult ; Blood Platelets ; Bone Marrow ; Busulfan ; Cyclophosphamide ; Disease-Free Survival ; Follow-Up Studies ; Graft vs Host Disease ; Granulocyte Colony-Stimulating Factor ; Humans ; Incidence ; Induction Chemotherapy ; Leukemia* ; Leukemia, Myeloid, Acute ; Melphalan ; Mucositis ; Myelodysplastic Syndromes ; Neutrophils ; Peripheral Blood Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prospective Studies ; Recurrence ; Stem Cell Transplantation* ; Stem Cells* ; Thiotepa

We have synthesized new platinum(H) analogs containing 1,2-diaminocyclohexane (dach) as a carrier ligand, 1,3-bis(diphenylphosphino) propane (DPPP) /1,2-bis(diphenylphosphino)ethane (DPPE) as a leaving group and nitrates to improve solubility. In the present study, the cytotoxicity of (Pt(trans-l-dach)(DPPP))cntdot2NO3 (KHPC-001) and (Pt(trans-l-dach)(DPPE)) cntdot 2NO3 (KHPC-002) was evaluated and compared on various P-388 cancer cell lines and porcine kidney cell line (LLC-PK1). The new platinum complexes demonstrated high efficacy on P-388 mouse leukemia cell line as well as cisplatin-resistant (P-388/CDDP) and adriamycin-resistant (P-388/ADR) P-388 cell lines. The intracellular platinum content was measured by a flame atomic absorption spectrophotometer (FAAS), and it was comparable to the results of IC50 of the three complexes on LLC-PK1I and P-388/S cells, while only DPPE compound was accumulated in high volume in P-388/ADR and P-388/CDDP cells. While the DNA-interstrand cross-links of KHPC-001, KHPC-002 and cisplatin were similar on P-388/S leukemia cells, these new platinum complexes were much less DNA cross-linking to a kidney derived cell line, LLC-PK1. These results indicate that KHPC-001 and KHPC-002 are a third-generation platinum complexes with potent antitumor activity and low nephrotoxicity.
Absorption ; Animals ; Cell Line ; Cisplatin ; Coordination Complexes* ; DNA ; Inhibitory Concentration 50 ; Kidney ; Leukemia ; Mice ; Nitrates ; Platinum ; Propane ; Solubility

OBJECTIVES: APL, which characteristically shows t(15:17), accompanies fatal coagulopathy during remission induction with systemic chemotherapy alone. ATRA, a derivative of vitamin A, can differentiate APL cells as well as HL-60 cells in vitro and induce higher rate of complete remission(CR). Hence, we assessed the effect of ATRA on remission induction and coagulopathy in APL patients. METHODS: (1) 42 patients diagnosed histologically in St. mary's hospital from June 1991 to June 1994 were included. (2) We compared the CR rate, the time required for restoration of derranged coagulation profiles, and the amount of coagulation factors including platelets among the chemotherapy group (control) and ATRA group. RESULTS: 1) There was no difference in CR rate between the control group and ATRA group [84.2%(16 out of 19) vs 87.0%(20 out of 23), p>0.05)] and also no difference between two subgroups of ATRA [ATRA with chemotherapy; 83.3%(10 out of 12) vs ATRA without chemotherapy; 90.9%(10 out of 11), p>0.05] 2) In the ATRA group, the CR rate of newly diagnosed patients was 82.4%(14 out of 17). The first relapsed patients (4) and the second (2) were all achieved CR. 3) The mean duration of coagulopathy, time to normalization of PT, aPTT, FDP, fibrinogen level, was 12.0+/-10.4, 11.1+/-10.2, 16.5+/-9.3, 15.4+/-10.2 days after chemotherapy alone and 4.5+/-4.4, 3.7+/-3.7, 8.9+/-6.1, 8.1+/-6.5 days in the ATRA group(p<0.05). The amount of fresh frozen plasma used in the ATRA group for the purpose of correction of coagulopathy were significantly lower than the control group(p<0.05). The incidence of profound coagulopathy during the remission induction treatment in the ATRA group was significantly lower than the control group[40% (8 out of 20) vs 96.7%(13 out of 15), p
Blood Coagulation Factors ; Drug Therapy ; Fibrinogen ; HL-60 Cells ; Humans ; Incidence ; Leukemia, Promyelocytic, Acute* ; Plasma ; Remission Induction* ; Tretinoin* ; Vitamin A

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.
Adult ; Bone Marrow Transplantation* ; Bone Marrow* ; Busulfan* ; Drug Therapy* ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia* ; Leukemia, Myeloid, Acute ; Melphalan* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Sepsis ; Stem Cell Transplantation ; Stem Cells ; Stomatitis ; Thiotepa*

We report five cases of cytomegalovirus infection in immunocompromised patients which were detected by either cytomegalovirus antigenemia assay or in situ hybridization. Four cases had leukemia and the other had chronic renal failure. All the three BMT recipients suffered from GvHD. Interestingly, there was an unique case of CMV disease without a history of BMT, which reminded us that CMV could attack immunocompromised patients who had not undergone transplantation, too. Four out of five cases died. We think that cytomegalovirus infection or disease should not be regarded as a minor problem in post-transplantation infection in Korea.
Adolescent ; Adult ; Antigens, Viral/*blood ; *Bone Marrow Transplantation ; Case Report ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/complications/*diagnosis ; Fatal Outcome ; Graft vs Host Disease/complications ; Human ; Immunocompromised Host ; In Situ Hybridization ; Kidney Failure, Chronic/complications ; Kidney Transplantation ; Leukemia/*complications/therapy ; Leukemia, Lymphocytic, Acute, L2/complications/therapy ; Leukemia, Myelocytic, Acute/complications/therapy ; Leukemia, Myeloid, Chronic/complications/therapy ; Male ; Viremia/*diagnosis

No abstract available.
Anemia, Iron-Deficiency* ; Erythropoietin* ; Iron* ; Tumor Necrosis Factor-alpha*

No abstract available.
Humans ; Staphylococcal Protein A*