Peripheral Blood Stem Cell Collection through Large Volume Leukapheresis after Mobilization with GM-CSF and/or G-CSF in Normal Healthy Donors / 대한혈액학회지

BACKGROUND: The use of colony stimulating factor (CSF) has increased to mobilize hematopoietic progenitor cells for allo-PBSCT. The most effective mobilization regimen has not yet defined. The authors analyzed the results of the mobilized PBSC collection through large volume leukapheresis from 38 normal healthy donors using three different regimens, namely, a single regimen with GM-CSF (Leucogen ), a concurrent use of GM-CSF and G-CSF (Leucostim ), and a sequential regimen with GM-CSF followed by G-CSF. METHODS: This study was done on 38 healthy donors from Sep. 1998 to Jan. 2001. One donor was mobilized with G-CSF alone, 9 with GM-CSF alone, 20 with concurrent regimen and 8 with sequential regimen. After 5 days of mobilization treatment, PBSCs were collected by large volume leukapheresis through femoral vein catheter. We compared the results of each collected progenitor cells and observed the side effects. RESULTS: The average WBC count before apheresis was 22.6+-11.0x103/uL and circulating CD34+cell percent was 1.31+-2.24%. Total 66 times with an average of 1.46+-0.61 of largevolume leukapheresis were performed for the 37 donors. The mean collected MNC count was 4.61+-2.77x108/kg, CD3+cell count was 2.95+-1.82x108/kg and CD34+cell count was 9.76+-12.42x106/kg. A significant side effect observed after large volume leukapheresis was thrombocytopenia showing decrease from 199.1+-52.2 to 80.7+-25.2x103/uL without any bleeding tendency. The mean collected MNC counts provoed to be significantly higher in combination groups with GM-and G-CSF than GM-CSF alone (P<0.05). The CD34+cell counts showed to be statistically higher in a sequential group compared to the concurrent and single regimen groups (P<0.05). CONCLUSION: A mobilization protocol with combination regimens of GM-CSF and G-CSF seemed to be superior to a single regimen with GM-CSF. Large volume leukapheresis through femoral vein catheter after mobilization with combination regimens of GM-and G-CSF in normal healthy donors was safe and proved to be an excellent. method to harvest stem cells.

Allogeneic Peripheral Blood Stem Cell Transplantation in Hematological Malignancies: Stem Cell Mobilization with GM-CSF alone or a combination of GM-CSF and G-CSF from Normal Healthy Donors / 대한혈액학회지

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) has been used in normal heathy donors to mobilize hematopoietic progenitors. Recently, it was reported that an addition of granulocyte-macrophage-CSF (GM-CSF) mobilized more primitive CD34+ subsets than did G- CSF alone. We investigated the result of the allogeneic peripheral blood stem cell transplantation (PBSCT) with stem cells mobilized with GM-CSF alone or a combination of GM-CSF and G-CSF from normal healthy donors in hematological malignancies. METHODS: Twenty-nine patients with hematologic malignancies had allogeneic PBSCT from normal sibling donors. Nine healthy donors were mobilized with GM-CSF (Leucogen (R)) alone and 20 with a combination of GM-CSF and G-CSF (Leucostim (R)). After 5~8 days of cytokine treatment, PBSCs were collected by large volume leukapheresis and analyzed. RESULTS: Stem cells were collected from the HLA matched normal healthy sibling donors. The mean harvested cell content was 8.74+/-3.22X10(8) MNCs/kg, 15.65+/-16.02X10(6) CD34+ cells/kg of the patients. There were significant differences in the harvested MNC count between mobilization group with GM-CSF alone and group with a bination of GM-CSF and G-CSF. Observed side effects of cytokine mobilization were myalgia (76%), headache (41%), febrile sense (24%) and skin rash (10%). These complications disappeared within 48 hours after discontinuation of cytokines. The median interval to achieve a WBC count>500/uL was 15.00+/-4.23 days, and 14.00+/-33.01 days to a platelet count>20,000/uL. The actual incidence of acute GVHD was 36.4%, 22.7%, and 4.5% for skin, GIT, and liver, respectively. Immunosuppressant responsive chronic GVHD developed in 63.1% (12/19) of assessable patients including 6 cases who had donor lymphocyte infusions. CONCLUSION: In this study, GM-CSF based cytokine mobilization was able to collect sufficient numbers of stem cells and allow rapid engraftment in the allogeneic PBSCT. Mobilization protocol with a combination of GM-CSF and G-CSF seemed to be superior to GM-CSF alone. Acute GVHD in patients with allogeneic PBSCT didn't appear to be more severe than in patients undergoing allogeneic BMT.

Allogeneic Peripheral Blood Stem Cell Transplantation with Stepwise Donor Lymphocyte Infusions in Mantle Cell Lymphoma Relapsed after Autologous PBSCT / 대한혈액학회지

Mantle cell lymphoma (MCL) is a distinctive clinicopathologic entity and represents 5~10% of all non-Hodgkin's Lymphoma (NHL). The median survival of patients with MCL is only 3 years, and none of the available conventional chemotherapy regimens appear curative. Encouraging results have been reported with high dose chemotherapy with stem cell transplantation for its treatment. Particularly, alloSCT appears to induce durable remission via graft-versus-lymphoma (GVL) effect. Donor lymphocyte infusions (DLIs), by virtue of graft-versus-tumor effect, have been shown to induce remissions in leukemia that recurs after alloSCT. But GVL effect of DLI has not been clearly established in NHL. We describe a patient with relapsed MCL shortly after high dose chemotherapy with autoSCT who was successfully treated with alloPBSCT. The patient presented with diffuse GI and spleeninvolvement at the time of alloPBSCT. The patient received Bu/Cy/VP-16 as preparative regimen followed by alloPBSCT. The patient received cyclosporin and methotrexate as GVHD prophylaxis. Prednisone was added after grade II GVHD. The patient had partial response by D+64. To enhance GVL effect, the patient received G-CSF primed DLI serially at D+64 and D+92. Grade IV GVHD developed 19 days after 2nd DLI and was partially controlled with a combination of cyclosporin, prednisone and mycophenolate mofetil. Clinical complete remission was observed at D+112, and maintained till last follow-up day (D+515). Our findings suggest that alloSCT and stepwise DLIs may offer a curative approach to MCL.

The Frequency and Clinical Significance of Multidrug Resistance-1 (MDR-1) Gene Expression in Acute Myeloid Leukemia / 대한혈액학회지

BACKGROUND: The expression of the multidrug resistance-1 (MDR-1) gene which encodes p-glycoprotein, is recognized as a biological mechanism possibly contributing to treatment failure in patients with acute myeloid leukemia (AML). Recent studies indicate its association with poor risk factors such as cytogenetic pattern and surface phenotype of blasts. We analyzed the role of MDR-1 gene expression in 36 chemo-naive AML patients. METHODS: In 36 patients, clinical data were reviewed and compared to MDR-1 gene expression, immunophenotyping results on CD7 & CD34, cytogenetic pattern and other suggestive prognostic factors. RESULTS: Median follow-up period was 150 days. The MDR-1 gene expression was observed in 19 out of 36 patients (52.8%). Significant correlation between MDR-1 gene and CD7 & CD34 expression was found. Sixteen out of 17 (94.1%) MDR-1 negative patients harbored favorable cytogenetic patterns, where as 11 out of 19 (57.9%) MDR-1 positive patients had favorable cytogenetic patterns. MDR-1 gene expression was not correlated to disease free survival (DFS), nor overall survival (OS) statistically although it has shown significant correlation to complete remission (CR) rate (P =0.001). CONCLUSION: We found that lack of MDR-1 gene expression was exclusively associated to favorable cytogenetic patterns in our study. In order to clarify the relationship between the role of MDR-1 gene and clinical outcome or other prognostic features, including cytogenetic pattern, further larger studies would be necessary.

Mantle cell lymphoma presented as multiple lymphomatous polyposis: clinical review of 4 cases / 대한내과학회지

Multiple lymphomatous polyposis(MLP) is an interesting clinical entity of non-Hodgkin's lymphoma(NHL) and is defined as B-cell lymphoma characterized by the presence of multiple lymphomatous polyps along the gastrointestinal tract. Recently MLP has been considered as a variant form of mantle cell lymphoma(MCL). The median survival of patients with MCL is only 3 years, and none of the available conventional chemotherapy regimens appears curative. Encouraging results have been reported with high dose chemotherapy with autoSCT and alloSCT for its treatment. We introduce 4 cases of MLP diagnosed as MCL by morphologic and immunologic method. The common clinical findings of these cases were splenomegaly (4/4), multiple intraabdominal lymphadenopathy (4/4), and advanced stage (3/4) at presentation. The overall remission duration was relatively short (5-27 months) and three of four cases relapsed after conventional chemotherapy or autologous stem cell transplant. Our report suggests that MCL presented as MLP is a high risk subgroup of NHL and more aggressive approach may be needed for cure.