Cancer Research and Treatment

Case Report

Second Primary Glioblastoma Multiforme Following Autologous Hematopoietic Stem Cell Transplantation in a Patient with Acute Myelogenous Leukemia: Eun-Oh Kim, Hee-Je Kim, Ki-Seong Eom, Byung-Sik Cho, Sung-Eun Lee, Seung-Ah Yahng, Jong-Wook Lee, Woo-Sung Min; Cancer Res Treat. 2011;43(3):195-198. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.195

Glioblastoma multiforme (GM) is one of the most aggressive primary brain tumors, and has a poor prognosis despite intensive treatment. GM is also the most malignant astrocytoma, with histopathological features that include cellular polymorphism, rapid mitotic activity, microvascular proliferation, and necrosis. The causes of GM remain obscure, but several reports have shown associations between GM and genetic alterations and radiation exposure. Furthermore, high-dose chemotherapy/radiotherapy with autologous stem cell transplantation is increasingly being used to treat patients with leukemia, and patients who undergo stem cell transplantation have a higher risk of solid tumor cancer development later in life. Based on these associations, we discuss GM development in a patient who underwent chemoradiotherapy conditioning prior to stem cell transplantation.

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Glioblastoma Multiforme in a Post Allogeneic Stem Cell Transplant Patient. A Case Report and Literature Review of Post Transplant Neurological Tumors
Abhijeet P. Ganapule, Sunita Susan Varghese, Geeta Chacko, I. Aparna, Auro Viswabandya
Indian Journal of Hematology and Blood Transfusion.2016; 32(S1): 192. CrossRef

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Original Articles

The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony-Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia: Young Joo Min, Cheol Won Suh, Keon Uk Park, Sung Soo Yoon, Chan Hyung Park, Hong Ghi Lee; Cancer Res Treat. 2003;35(1):66-68. Published online February 28, 2003; DOI: https://doi.org/10.4143/crt.2003.35.1.66

Abstract PDF: PURPOSE
This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo-skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML.

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Prognostic Implications of Cytarabine Dose in Consolidation Chemotherapy for the Patients with Acute Myelogenous Leukemia: Jung Hee Lee, Je Hwan Lee, Kyoo Hyung Lee, Hyeseung Bahng, Jin Hee Ahn, Jung Shin Lee, Sang Hee Kim, Woo Kun Kim; J Korean Cancer Assoc. 2000;32(5):954-961.

Abstract PDF: PURPOSE
Increasing the dose of cytarabine in consolidation chemotherapy has been suggested to improve treatment outcome of the patients with acute myelogenous leukemia (AML) in complete remission (CR). We studied an effect of cytarabine dose in consolidation chemotherapy on the survival times.
MATERIALS AND METHODS
From 1989 to 1998, AML patients in CR who received two or more courses of consolidation chemotherapy were included. At the first course of consolidation chemo therapy, all patients received standard dose of cytarabine (100 or 200 mg/m2/day by a continuous infusion for 5 days) plus anthracyclines. At the second or third course, one of three dose levels of cytarabine was given with anthracyclines. Three dose levels of cytarabine were standard dose (SD), intermediate dose (ID, 1 or 2 g/m2/day by a 3-hour infusion for 5 days), and high dose (HD, 3 g/m2 in a 3-hour infusion every 12 hours for total six doses). We retrospectively reviewed clinical records of study patients.
RESULTS
64 patients were included. The median follow-up duration of alive patients was 1,143 days. Estimated 3-year overall survival times were 24% in SD group, 41% in ID group and 56% in HD group (P=0.737). Estimated 3-year disease free survival times were 18%, 16% and 44% in each group (P=0.592). There was no significant difference in toxicity of consolidation chemotherapy between three groups.
CONCLUSION
Although the survival times showed a trend to be longer in the patients who received higher dose of cytarabine as consolidation chemotherapy, there were no statistically significant differences.

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A Clinical Study of Pediatric Myelodysplastic Syndrome: Application of International Prognostic Scoring System and the Review of the Korean Literature: Hoon Kook, Chan Jong Kim, Weon Sang Yoon, Na Eun Ryu, Kyoung Joong Chung, Tai Ju Hwang; J Korean Cancer Assoc. 2000;32(1):178-190.

Abstract PDF: PURPOSE
Myelodysplastic syndrome (MDS) in children needs to be elucidated in terms of clinical characteristics, natural history, the most effective treatment and prognostic factors, as the disease is very rare and its definition and classification has not reached a consensus by many physician. This study was aimed to describe the characteristics and the disease courses of Korean children with MDS, and to analyze the usefulness of prognostic scoring systems in the prediction of transformation to acute myelogenous leukemia (AML) and overall survival among subgroups.
MATERIALS AND METHODS
Fourteen children with MDS seen at Chonnam University Hospital and additional 59 patients identified by the review of Korean literature were evaluated to define clinical characteristics and disease courses. Kaplan-Meier (K-M) probability of leukemic transformation and overall survival were plotted. FAB subtypes, subgroups by Boumemouth Scoring System (BSS), and International Prognostic Scoring System (IPSS) risk groups were compared to predict transformation to AML and overall survival.
RESULTS
The median age of 14 patients was 36.5 months. The sex ratio was 3.7:1 (M: F). The frequency of FAB subtypes in Korea was similar to that of other countries except for higher proportion of RA (37%). K-M 3-yr probability of AML transformation and survival for Korean patients were 54.7%, and 49.8%, respectively. Although FAB system, BMS and IPSS were all capable of discriminating subgroups in the prediction of AML transformation and survival, they did not reach the significant level possibly due to small number of patients assigned to each subgroup.
CONCLUSION
The clinical characteristics of Korean children with MDS were not different from those of other countries. This study showed the high rate of AML transformation and poor survival in children with MDS.

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Expression of Multidrug Resistant Genes in Bone Marrow Mononuclear Cells of Patients with Myeloid Leukemia: Seok Goo Cho, Il Ho Yang, Hyeon Seok Eom, Chang Gi Min, Hee Je Kim, Dong Wook Kim, Jong Wook Lee, Chi Wha Han, Woo Sung Min, Won Il Kim, Chun Choo Kim; J Korean Cancer Assoc. 1999;31(1):153-164.

Abstract PDF: PURPOSE
Multidrug resistance mediated by several drug resistant genes impedes the successful outcome of anti-cancer chemotherapy. In this study, we investigated the expressions of drug resistant genes encoding multidrug resistance (MDR1), multidrug resistance-associated protein (MRP), topoisomerase I (Topo I), topoisomerase II g (Topo II a) in narmal volunteers (n=12) in and patients with myeloid leukemia (n=34). Material and Method: We compared the levels of their transcripts in bone matrow mononuclear cells by semiquantitative RT-PCR. The amount of specific transcripts was represented as the optical density ratio of PCR product of target gene to that of B2- microglobulin (MG). Twenty patients of acute myelogenous leukemia (eight in remission state, twelve in refractory) and fourteen patients of chronic myelogenous leukemia (nine in chronic phase and five in blastic crisis) were examined. Twelve normal healthy persons were compared with leukemic patients.
RESULTS
The expression levels of all resistant genes in normal volunteers were relatively high as those of AML patients. Regardless of the disease status including remission status of AML (complete remission versus refractory) and the phase of CML (chronic phase versus blastic phase), the expression levels of all resistant genes in patients with CML were significantly lower than in the patients with AML (p < 0.05). Of interest, the patients with refractary AML did not show any statistical difference in comparison with normal controls and even the patients with AML in complete remission. Among the four drug resistant genes, the optical density ratio of MDRl was significantly lower than that of any other genes (p<0.05). Using HL-60 cell line, we compared the changes of various resistant gene expressions before and after differentiation induced by dimethylsulfoxide. The expressions of resistant genes declined in paralle1 with granulocytic differentiation, suggesting that the induction of cell differentiation might make leukemic cells susceptible to chemotherapeutic agents.
CONCLUSION
It is impossibble to explain the mechanism of drug resistance by comparing the level of drug resistant gene expression between nonnal subjects and patients with myeloid leukemias. Therefore, we suppose that longitudinal study of drug resistant gene expression is necessary to demonstrate the development of drug resistant during chemotherapy.

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Clinical Trial

The Effect of Cytosine Arabinoside and Daunorubicin(AD) Combination Chemotherapy in Acute Myelogeous Leukemia: Chang Hoon Moon, Sung Hyun Kim, Hyung Ryoul Park, Jung Hwan Cho, Hyok Chan Kwon, Jae Seok Kim, Hyo Jin Kim; J Korean Cancer Assoc. 1998;30(4):842-852.

Abstract PDF: PURPOSE
Important advances in the treatment of acute myelogenous leukemia have been made with the introduction of cytosine arabinoside(ara-C) and anthracycline(daunorubicin) over the past 20 years. Currently, 50 to 85% of patients with acute myelogenous leukemia achieve complete remission with induction chemotherapy consisting of ara-C and daunorubicin. About 25% of complete responders will have extended long-term survival and may be cured. Therefore we treated patients having acute myelogenous leukemia with AD(7+3) regimen and analyzed factors complete remission rate, remission duration, and survival duration.
MATERIALS AND METHODS
Induction therapy; Thirty seven patients with previously untreated acute myelogenous leukemia treated with AD(7+ 3) regimen(ara-C, 200 mg/m2/d by continuous infusion for seven days, and daunorubicin, 45 mg/m2/d for 3 days). The second course of therapy was AD(5+2), if the patients failed to enter remission. Consolidation therapy; three cycles of consolidation chemotherapy were administrated with at least 4 week interval following remission. Course 1; ara-C at 100 mg/m2 by continuous infusion every 12 hour for five days, 6-thioguanine at 100 mg/m2/day orally for 5 days. Course 2; ara-C is same as course 1, vincristine at 1.2 mg/m2(maximum 2 mg) by bolus injection for 1 day, prednisolone at 40 mg/m'(maximum 60 mg) orally for 5 days. Course 3; ara-C is same as course 1, daunorubicin at 45 mg/m2 by 1 hour infusion for 2 days.
RESULT
62.2 percent of the 37 patients entered complete remission. The remission duration for all patients in complete remission ranged from 2 months to 63+ months, with the median of 15.1 months. The median duration of survival in complete responder group was 23.3 months. Among various prognostic factors, females and groups with normal chromosome and t(8;21) or t(15;17) had significantly higher complete remission rate than males and groups with other chromosomal abnormalities, respectively. Factors influencing on survival duration were female, normal chromosome, t(8;21) or t(15;17), Auer rod-positive, and peripheral blast % less than 50% at diagonosis. Groups with Auer rod-positive, normal chromosome, and t(8;21) or t(15;17) also had significantly longer remission duration.
CONCLUSION
Combination chemotherapy with cytosine arabinoside and daunorubicin is a effective regimen for acute myelogenous leukemia as much as other regimen for acute myelogenous leukemia. Further clinical trials for effective treatment regimen are necessary to increase the complete remissioin rate.

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Original Articles

Study on Growth Suppression Effect of Vetamin D3 Mediated by Transfrorming Growth Factor-B1(TGF-B1) in Acute Myelogenous Leukemic Cell: Chul Won Jung, Sang Jae Lee, Myung Joo Ahn, Tae Joon Jung, In Soon Kim, Il Young Choi, Jae Koo Seol, Eun Sil Kim, Byung Kook Kim, Young Yeol Lee; J Korean Cancer Assoc. 1998;30(4):827-841.

Abstract PDF: PURPOSE
Vitamin D3 was shown to arrest the growth of acute myelogenous leukemic cells and transforming growth factor- B1 (TGF- B1) was reported to be involved in the mechanism of vitamin D3. We studied the growth inhibitory effect of 1,25(OH)2-vitamin D3(C) and its analogue (EB1089) in leukemic cell lines and the changes in the secretion or the activation of TGF-B1 in the supernatant and the status of TGF-B1 type II receptor.
MATERIALS AND METHODS
Growth inhibition by vitamin D3 and TGF-B1 in 5 leukemic cell lines (HEL, HL-60, U937, KG-1, K562) were assessed with clonogenic and [3H]thymidine assay respectively. TGF-B type II receptor status was examined by Southern and Northern blotting. The concentrations of TGF- B1 in the supernatant were quantitated by enzyme immunoassay.
RESULTS
The growth of HEL, HL-60, U937 were inhibited in a dose-dependent fashion by both C and EB1089, more markedly by the latter. Anti-TGF-B neutralizing antibody partially reversed the growth inhibition. TGF-B1 markedly inhibited the growth of HEL, U937, KG-1, SNU-16 dose dependently while HL-60 and K562 showed no growth inhibition. HEL secreted latent TGF- 1 and HL-60 activated latent TGF- B1 or secreted active TGF-B1 irrespective of the treatment with vitamin D3. In U937, vitamin D3 increased the concentration of both active and latent TGF-B1. Deletion or abnormal expression of TGF- B type II receptor gene was not found in the 5 cell lines examined.
CONCLUSION
Vitamin D3 has various pattern of growth inhibition in acute myelogenous leukemia and inhibits the growth of some cell lines by secretion or activation of TGF-B1. Abnormality of TGF-B type II receptor DNA or mRNA seems to be rare.

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A Case of Acute Myelogenous Leukemia during Pregnancy: Jae Gyoon Lee, Sung Hyun Yang, Heung Tae Kim; J Korean Cancer Assoc. 1997;29(3):516-521.

Abstract PDF: The incidence of acute leukemia in pregnancy is rare. The treatment of acute leukemia during pregnancy is complicated and therapeutic options must be made with each individual patient. Complete remission can now be achieved in 60 to 70% of previously untreated adults with acute myelogenous leukemia (AML). Antileukemic chemotherapy can be administered safely during the second and third trimesters. Cytarabine (ara-C) and anthracycline has not been associated with birth defect. When a pregnant woman presents with acute leukemia, chemotherapy should be recommended as vigorously as in the non- pregnant woman. We reported a case of AML during pregnancy. The patient recieved induction chemotherapy with ara-C and idarubicin. The baby was delivered at 33 weeks of gestation and had transient neutropenia. The mother received consolidation chemotherapy after achievement of complete remission.

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