• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.319-327
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• 2023

Purpose: Patients with hematological malignancies are at an increased risk of severe infection with coronavirus disease 2019 (COVID-19). However, developing an adequate immune response after vaccination is difficult, especially in patients with lymphoid neoplasms. Since the long-term effects of the BNT162b2 vaccine are unclear, the humoral immune response 5 months after the two vaccinations in patients with hematological disorders was analyzed. Materials and Methods: Samples were collected from 96 patients vaccinated twice with BNT162b2 and treated with at least one line of an antitumor or immunosuppressive drug in our hospital from November 2021 to February 2022. Serum anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) spike (S) antibody titers were analyzed. Patients were age- and sex-matched using propensity matching and compared with a healthy control group. Patients with serum anti-SARS-CoV-2 S antibodies were defined as 'responder' if >50 U/mL. The patients had B-cell non-Hodgkin lymphoma (B-NHL), multiple myeloma, chronic myeloid leukemia, etc. Results: Patients had significantly low antibody levels (median, 55.3 U/mL vs. 809.8 U/mL; p<0.001) and a significantly low response rate (p<0.001). Multivariate analysis showed that patients with B-NHL, aged >72 years, were associated with a low response to vaccination. There were no significant differences between patients with chronic myeloid leukemia and healthy controls. Conclusion: Our study shows that patients with hematological disorders are at risk of developing severe COVID-19 infections because of low responsiveness to vaccination. Moreover, the rate of antibody positivity differed between the disease groups. Further studies are warranted to determine an appropriate preventive method for these patients, especially those with B-NHL.

• Journal of Chest Surgery
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• v.40 no.9
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• pp.617-623
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• 2007

Background: Invasive pulmonary aspergillosis, a frequent fungal infection in immunocompromised patients, is known to have a poor prognosis despite the use of antifungal therapy in leukemic patients. We studied the outcome of surgical resection of invasive pulmonary aspergillosis where bleeding tendency, localized recurrence of infection, and incidence could be reduced. Material and Method: We retrospectively reviewed 14 patients with a hematological malignancy where invasive pulmonary aspergillosis was diagnosed during the 10 years between 1998 and 2007. From the medical records, we reviewed the type and treatment of the hematological malignancy, including the diagnostic methods of invasive pulmonary aspergillosis, the preoperative hematological conditions and their management, and the surgical methods and records. We also analyzed the development of postoperative complications and patient mortality, the recurrence of postoperative invasive pulmonary aspergillosis, and if the patients had a bone marrow transplant. Result: Fourteen patients with invasive pulmonary aspergillosis and a hematological malignancy underwent a pulmonary lobectomy. One patient had a complication of bronchopleural fistula, but there were no other serious complications such as bleeding or wound infection, and none of the patients died postoperatively. Conclusion: We have shown that pulmonary lobectomy is a safe and effective therapy for invasive pulmonary aspergillosis in patients with hematological malignancies that allow further treatment of the hematological malignancy.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.1
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• pp.11-23
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• 2009

Chromosomal rearrangements are major pathology in hematological malignancies. The detection of minimal residual disease (MRD) for these gene rearrangements helps in monitoring treatment outcomes and predicting prognosis of patients. Recently, quantification of these gene transcripts based on real-time quantitative polymerase chain reaction (RQ-PCR) has been used as MRD detection. The purpose of this study is to ensure the usefulness of the RQ-PCR technique for detecting MRD in hamatological malignancy patients. The patients had been diagnosed to AML1-ETO positive AML, PML-RARa positive AML and BCR-ABL positive MPN at Chonnam National University Hwasun Hospital from Jan. 2006 to Aug. 2008. The fusion transcript was quntified by RQ-PCR and analyzed in comparison to conventional cytogenetics, FISH and RT-PCR. The fusion gene transcript was quantified by RQ-PCR in 57 samples from 14 patients with AML1-ETO positive AML, 79 samples from 27 patients with PML-RARa positive AML and 108 samples from 36 patients with CML. At diagnosis, the quantitative fusion transcripts for AM1-ETO, PML-RARa and BCR-ABL showed the range of 0.485552651~10.82233683 (mean 3.782217131, SD 2.998052348), 0.005300395~0.29267494 (mean 0.056901315, SD 0.080131381) and 0.1293929~12.94826849 (mean 1.701935665, SD 2.200913158). The increase of AML1-ETO fusion gene transcripts preceded morphologic relapse in two patients. Quantification of fusion gene transcripts by RQ-PCR could detected MRD in samples which were negative by in cytogenetic analysis or FISH. Our findings indicated that quantitative analysis of AML1-ETO, PML-RARa and BCR-ABL transcripts by RQ-PCR might be a useful tool for the monitoring of minimal residual disease in hematological malignancies.

• BMB Reports
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• v.51 no.9
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• pp.444-449
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• 2018

Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4843-4847
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• 2015

To date, cytotoxic effects of flavonoids in various cancer cells are well accepted. However, the intracellular signaling cascades triggered by these natural compounds remain largely unknown and elusive. In this mini-review, the multiplicity of molecular targets of flavonoids in blood cancer cells is discussed by demonstrating the involvement of various signaling pathways in induction of apoptotic responses. Although these data reveal a great potential of flavonoids for the development of novel agents against different types of hematological malignancies, the pleiotropic nature of these compounds in modulation of cellular processes and their interactions certainly need unraveling and further investigation.

• Biomedical Science Letters
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• v.18 no.2
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• pp.131-138
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• 2012

Autologous peripheral blood stem cell transplantation (PBSCT) has been used as a major treatment strategy for hematological malignancies. The number of CD34 positive cells in the harvested product is a very important factor for achieving successful transplantation. We studied the factors that can predict the number of CD34 positive cells in the harvested product of acute myelocytic leukemia (AML), multiple myeloma (MM) and Non-Hodgkin's lymphoma (NHL) patients after mobilizing them with chemotherapy plus G-CSF. A total of 73 patients (AML 19 patients, MM 28 patients, NHL 26 patients) with hematological malignancies had been mobilized with chemotherapy and granulocyte colony-stimulating growth factor from April, 2000 to February, 2012. Group's characteristics, checkup opinion of pre-peripheral blood on the day of harvest & outcome of PBSC were analyzed and evaluated using SPSS statistics program after grouping patients as below; group 1: CD34 cell counts < $2{\times}10^6/kg$ (n=16); group 2: $2{\times}10^6/kg{\leq}CD34$ cell counts < $6{\times}10^6/kg$ (n=32); group 3: CD34 cell counts ${\geq}6{\times}10^6/kg$ (n=25). We analyzed the clinical characteristics, the peripheral blood (PB) parameters and the number of CD34 positive cells in the PB and their correlation with the yield of CD34 positive cells collected from the mobilized patients. The total number of leukapheresis sessions was 263 (mean: 3.55 session per patient), and the mean number of harvested CD34 positive cells per patient was $7.37{\times}10^6/kg$. The number of CD34 positive cells in product was significantly correlated with the number of platelet and CD34 positive cells in peripheral blood (P<0.05). The number of PB CD34 positive cells was the best significant factor for the quantity of harvested CD34 positive cells on the linear regression analysis (P<0.05). Many factors could influence the mobilization of peripheral blood stem cells. Platelet count and PB CD34 positive cells count were the two variables which remained to be significant in multivariate analysis. Therefore, the number of platelet and CD34 positive cells in peripheral blood on the day of harvest can be used as an accurate predictor for successful peripheral blood stem cell collection.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2523-2526
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• 2012

Introduction: Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. Methods: A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. Results: A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being ${\leq}50$. Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/$mm^3$, 34 (26%) one between 100-300 cells/$mm^3$ and 40 (31%) an ANC greater than 300 cells/$mm^3$. Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC <100 cells/$mm^3$ were more likely to die than patients with ANC >300 cells/$mm^3$ by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. Conclusion: Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6399-6402
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• 2013

Hematological malignancies (HM) are a group of neoplasms derived from the cells of the bone marrow and lymphatic system. Genetic factors leading to susceptibility to HM have been investigated for years but little is known yet. Low molecular weight polypeptide (LMP) 2 and LMP7 genes are important subunits of the immunoproteasome and play significant role in antigen presentation. The polymorphisms of LMP genes have been reported to be risk factors for various types of diseases. The aim of this study was to investigate the association of LMP2 and LMP7 polymorphisms with the occurrence of particular types of HM. A total of 132 patients with HM and 130 control subjects were investigated. No significant difference was obtained in the distribution of genotype and allele frequencies of LMP7 gene in HM patients and the control group. On the other hand, the prevalence of LMP2-AA genotype was found to be higher in acute myeolid leukemia (AML) patients while it was significantly lower in multiple myeloma (MM) cases than in the control subjects. Our results suggested that LMP7 could not be a risk factor for susceptibility to HM, whereas LMP2 polymorphisms could play a role in the development of AML and MM.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5983-5986
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• 2015

Background: Serum 25-hydroxyvitamin D insufficiency is very common in Pakistan and is often related to inferior prognosis in some cancers but limited data exist for hematopoietic malignancies. This study was conducted to determine the vitamin D insufficiency in B-chronic lymphoid leukemia (CLL) cases at the time of presentation and its possible correlation with clinical staging, hematological parameters and biochemical markers. Materials and Methods: This descriptive cross sectional study was carried at Liaquat National Hospital from January 2011 to June 2013. Sixty patients with B-chronic lymphoid leukemia were enrolled. Complete blood count, vitamin D levels, serum urea, creatinine, uric acid and LDH levels were assessed. Data were compiled and analyzed using SPSS version 21. Results: Out of 60 patients, 42 (70%) were male and 18 (30%) were female. Mean age was $59.0{\pm}9.2years$. The frequency of vitamin D insufficiency was found to be 56.7%. Overall insufficiency was more frequently seen in male gender (40%). Vitamin D insufficiency demonstrated a positive association with low lactate dehydrogenase levels (P=0.005). No links were established with age, clinical stage, hematological and other biochemical markers. Conclusions: Vitamin D insufficiency is high compared with Western studies. Whether normalization of vitamin D insufficiency in deficient B-CLL patients could improve the clinical outcome or delay disease progression will require further studies.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6599-6603
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• 2015

Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.