Long-term follow-up of cancer and catastrophic diseases in hematopoietic stem cell donors: a comprehensive matched cohort study.

Hematopoietic stem cell (HSC) transplantation, using either bone marrow (BM) or peripheral blood stem cells (PBSC), is a well-established therapy for various hematologic and non-hematologic diseases. However, the long-term health outcomes after HSC donation remain a major concern for several potential donors. Thus, we aimed to conduct a matched cohort study of 5003 unrelated donors (1099 BM and 3904 PBSC) and randomly selected 50,030 matched controls based on age, sex, and resident area from the donor registry between 1998 and 2018. The medical insurance claims of all the participants were retrieved from the Taiwan National Health and Welfare Data Science Center after de-identification. Our findings revealed no differences in the incidence of cancer, death, and catastrophic diseases between HSC donors and matched healthy participants during long-term follow-up. Kaplan-Meier curves depicting the cumulative incidence of cancer and overall mortality throughout the follow-up period also demonstrated similar outcomes between donors and non-donors. In conclusion, our results indicate that HSC donation, whether through BM or PBSC, is safe and not associated with an increased risk of cancer, death, or catastrophic diseases. These findings provide valuable information for counseling potential HSC donors and for long-term management of HSC donor health.

Erratum: Barsasella et al. Sleep Quality among Breast and Prostate Cancer Patients: A Comparison between Subjective and Objective Measurements. Healthcare 2021, 9, 785.

The authors wish to make the following erratum to this paper [...].

Sleep Quality among Breast and Prostate Cancer Patients: A Comparison between Subjective and Objective Measurements.

Breast and prostate cancer patients may experience physical and psychological distress, and a possible decrease in sleep quality. Subjective and objective methods measure different aspects of sleep quality. Our study attempted to determine differences between objective and subjective measurements of sleep quality using bivariate and Pearson's correlation data analysis. Forty breast (n = 20) and prostate (n = 20) cancer patients were recruited in this observational study. Participants were given an actigraphy device (ACT) and asked to continuously wear it for seven consecutive days, for objective data collection. Following this period, they filled out the Pittsburgh Sleep Quality Index Questionnaire (PSQI) to collect subjective data on sleep quality. The correlation results showed that, for breast cancer patients, PSQI sleep duration was moderately correlated with ACT total sleeping time (TST) (r = -0.534, p < 0.05), and PSQI daytime dysfunction was related to ACT efficiency (r = 0.521, p < 0.05). For prostate cancer patients, PSQI sleep disturbances were related to ACT TST (r = 0.626, p < 0.05). Both objective and subjective measurements are important in validating and determining details of sleep quality, with combined results being more insightful, and can also help in personalized care to further improve quality of life among cancer patients.

Autologous stem cell transplantation in multiple myeloma: Post-transplant outcomes of Taiwan Blood and Marrow Transplantation Registry.

BACKGROUND/PURPOSE: Multiple myeloma (MM) is a monoclonal plasma cell malignancy. The primary choice of treatment for MM is induction therapy followed by autologous stem cell transplantation (ASCT). This study aimed to analyze the treatment efficacy of ASCT in a Taiwanese cohort and evaluate possible prognostic factors. METHODS: From the database of the Taiwan Blood and Marrow Transplantation registry, data on 396 patients with MM who underwent ASCT were reviewed. RESULTS: The average age of participants was 54.8 years, and there were more men than women (57.6% vs. 42.4%). Most patients were diagnosed with IgG-type myeloma (52.4%), followed by IgA-type (23.2%) and light-chain type (21.4%). Patients with Durie Salmon Staging System (DSS) III disease accounted for 61.9% of the study cohort, while 23.7% had stage II and 14.4% had stage I disease. The median progression-free survival (PFS) and overall survival (OS) after ASCT were 46.5 months and 70.4 months, respectively. DSS III was a poor prognostic factor affecting both PFS and OS with a duration of 35.9 months and 69.0 months, respectively, compared with the other two stages (p = 0.006 and p = 0.03, respectively). In addition, patients with better treatment response before ASCT had better PFS and OS compared with those who did not show a response (both p < 0.0001). The overall incidence of organ toxicities associated with transplantation was low. CONCLUSION: In conclusion, our cohort showed that myeloma patients with early DSS and better treatment response before ASCT had better long-term survival outcomes.

Opposite Regulation of CHOP and GRP78 and Synergistic Apoptosis Induction by Selenium Yeast and Fish Oil via AMPK Activation in Lung Adenocarcinoma Cells.

Selenium has been intensively studied for the use of cancer prevention and treatment. However, the clinical effects are still plausible. To enhance its efficacy, a combinational study of selenium yeast (SY) and fish oil (FO) was performed in A549, CL1-0, H1299, HCC827 lung adenocarcinoma (LADC) cells to investigate the enhancement in apoptosis induction and underlying mechanism. By sulforhodamine B staining, Western blot and flow cytometric assays, we found a synergism between SY and FO in growth inhibition and apoptosis induction of LADC cells. In contrast, the fetal lung fibroblast cells (MRC-5) were unsusceptible to this combination effect. FO synergized SY-induced apoptosis of A549 cells, accompanied with synergistic activation of AMP-activated protein kinase (AMPK) and reduction of Cyclooxygenase (COX)-2 and ß-catenin. Particularly, combining with FO not only enhanced the SY-elevated proapoptotic endoplasmic reticulum (ER) stress marker CCAAT/enhancer-binding protein homologous protein (CHOP), but also reduced the cytoprotective glucose regulated protein of molecular weight 78 kDa (GRP78). Consequently, the CHOP downstream targets such as phospho-JNK and death receptor 5 were also elevated, along with the cleavage of caspase-8, -3, and the ER stress-related caspase-4. Accordingly, inhibition of AMPK by compound C diminished the synergistic apoptosis induction, and elevated CHOP/GRP78 ratio by SY combined with FO. The AMPK-dependent synergism suggests the combination of SY and FO for chemoprevention and integrative treatment of LADC.

Presence of pleural effusion is associated with a poor prognosis in patients with epidermal growth factor receptor-mutated lung cancer receiving tyrosine kinase inhibitors as first-line treatment.

AIM: This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs). METHODS: Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively. RESULTS: A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively]. CONCLUSION: The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients.

Prognostic significance of flow cytometric residual disease, dysregulated neutrophils/monocytes, and hematogones in adult acute myeloid leukemia in first remission.

Fifty-one consecutive non-M3 acute myeloid leukemia (AML) patients who had achieved morphologic complete remission (mCR) after induction chemotherapy were enrolled in the present study. Three characteristics of bone marrow (BM) composition analyzed by flow cytometry were combined to determine the prognostic impact. A standardized panel of reagents was used to detect residual disease of aberrant myeloid progenitor cells (RD), identify neutrophils/monocytes with dysregulated immunophenotype (dysregulated neutro/mono) and quantify the appearance of CD34(+) B-progenitor-related cluster (hematogones) simultaneously in post-induction BM of adult AML patients. Patients who had detectable RD ≥0.2 % exhibited significantly lower median leukemia-free survival (LFS) than those who did not (13.5 vs. 48.0 months; P = 0.042). Dysregulated neutro/mono abnormalities assessed by this flow cytometric scoring system (FCSS ≥2) predicted shorter LFS (8.0 vs. 39.0 months; P = 0.008). While B-progenitor-related cluster size ≥5 % predicted improved outcome, with longer LFS (not reached vs. 13.5 months; P = 0.023) and better overall survival (not reached vs. 24.0 months; P = 0.027). The proposed RD/dysregulated neutro/mono/hematogones score showed a new risk groups with different LFS in the overall patients (P = 0.0006) as well as in the subgroup of intermediate cytogenetic risk (P = 0.001). The RD/dysregulated neutro/mono/hematogones score assessed by flow cytometry for adult AML in mCR may offer a rapid and practical risk assessment providing better refinement in risk-adapted management after induction chemotherapy.

Thalidomide treatment in a myelofibrosis patient with leukemia transformation.

Primary myelofibrosis is a clonal disease of chronic myeloproliferative neoplasm, and is a progressive clinical course with short median survival of less than 5 years after diagnosis. Leukemic transformation occurs in 8-23 % of myelofibrosis patients, and survival is about 3 months after transformation to leukemia. Thalidomide, an oral immunomodulatory drug, has been used effectively in the treatment of primary myelofibrosis, in which some patients could become transfusion independent, and showed improvement in thrombocytopenia and reduction in spleen size. Here, we report a patient with primary myelofibrosis with leukemic transformation who survived for more than 6 years with thalidomide monotherapy. Thalidomide may be beneficial for some myelofibrosis patients with leukemic transformation for whom intensive chemotherapy is not indicated.

A postmarketing surveillance study on erbitux (cetuximab) in patients with metastatic colorectal cancer refractory to irinotecan-containing treatment.

OBJECTIVE: This postmarketing surveillance study evaluated the safety and efficacy of cetuximab therapy in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in Taiwan. METHODS: Patients with EGFR-expressing mCRC who had failed prior irinotecan-based chemotherapy and were receiving cetuximab therapy were monitored for treatment efficacy and safety from the time of first infusion until 28 days after the last infusion regardless of the reasons fordiscontinuation. The study followed 269 patients for approximately 2 years. RESULTS: No unexpected adverse events associated with cetuximab therapy were reported, and most events were grade 1 or 2. The most common drug-related adverse events of any grade were rash (21.6%) and dermatitis acneiform (4.8%). Reported grade 3/4 events were rash (4.5%), dermatitis acneiform (0.4%), and diarrhea (0.4%). Cetuximab treatment for patients receiving second-/third-line (177 patients) or above therapy (92 patients) was associated with a median progression-free survival time of 3.37 and 3.90 months, respectively, and a median overall survival time of 17.6 and 21.1 months, respectively. The response rates for the second-/third-line treatment and fourth-line or above cetuximab treatment groups were similar (21.5% vs 17.4%; P = 0.428). CONCLUSION: Cetuximab showed no unexpected safety findings and was efficacious in treating patients with EGFR-expressing mCRC in community practice in Taiwan.

Down-regulation of the oncogene PTTG1 via the KLF6 tumor suppressor during induction of myeloid differentiation.

The aberrant expression of proto-oncogenes is involved in processes that are responsible for cellular proliferation and the inhibition of myeloid differentiation in acute myeloid leukemia (AML). Pituitary Tumor-Transforming gene 1 (PTTG1), an oncogenic transcription factor, is abundantly expressed in various human cancers and hematopoietic malignancies. However, its expression in normal leukocytes and most normal tissues is very low or undetectable. The mechanism by which PTTG1 overexpression modifies myeloid cell development and promotes leukemogenesis remain unclear. To investigate the mechanistic links between PTTG1 overexpression and leukemia cell differentiation, we utilized phorbol 12-myristate 13-acetate (PMA), a well-known agent that triggers monocyte/macrophage differentiation, to analyze the expression patterns of PTTG1 in PMA-induced myeloid differentiation. We found that PTTG1 is down-regulated at the transcriptional level in PMA-treated HL-60 and THP1 cells. In addition, we identified a binding site for a tumor suppressor protein, Kruppel-like factor 6 (KLF6), in the PTTG1 promoter. We found that KLF6 could directly bind and repress PTTG1 expression. In HL-60 and THP1 cells, KLF6 mRNA and protein levels are up-regulated with a concordant reduction of PTTG1 expression upon treatment with PMA. Furthermore, KLF6 knockdown by shRNA abolished the suppression of PTTG1 and reduced the activation of the differentiation marker CD11b in PMA-primed cells. The protein kinase C (PKC) inhibitor and the MAPK/ERK kinase (MEK) inhibitor significantly blocked the potentiation of PMA-mediated KLF6 induction and the down-regulation of PTTG1, indicating that PTTG1 is suppressed via the activation of PKC/ERK/KLF6 pathway. Our findings suggest that drugs that increase the KLF6 inhibition of PTTG1 may have a therapeutic application in AML treatment strategies.

Impact of donor characteristics and HLA matching on survival of chinese patients with hematologic malignancies undergoing unrelated hematopoietic stem cell transplantation.

We retrospectively analyzed the impact of donor characteristics and HLA matching on outcomes in Chinese patients undergoing unrelated hematopoietic stem cell transplantation (HSCT). A total of 693 patients with hematologic malignancies who underwent HSCT between 2005 and 2010 had available survival data at 100 days or 1 year posttransplantation in the Buddhist Tzu-Chi Stem Cell Center database. The overall survival rates at 100 days and 1 year were 83.3% and 65.2%, respectively. Mismatches of HLA-A, -B, and -DRB1 at the antigen or allele level, along with inadequate cell dose, were associated with a significant risk of mortality (hazard ratio [HR] = 2.36, P < .001; HR = 1.44, P = .005; and HR = 2.20, P = .009, respectively). In 107 donors with matched HLA-A, -B and -DRB1 and known HLA-C match status, 22.4% had an HLA-C antigen mismatch, resulting in an HR of 2.87 for mortality relative to complete 8/8 matches (P = .005). Recipients with unknown HLA-C match status also had a significantly worse outcome (HR = 1.73; P = .039). Multivariate analysis revealed that cell dose and HLA-A, -B, -C, and -DRB1 antigen match status significantly affected the final outcome of survival (P = .012 and <.001, respectively). Our data indicate that HLA-C match status should be confirmed before HSCT from an unrelated donor. Inadequate cell dose remains an important determinant of poor transplantation survival. Further studies to elucidate the importance of matching of specific HLA loci are needed to better understand the risk of HSCT and improve patient outcomes.

The role of donor characteristics and post-granulocyte colony-stimulating factor white blood cell counts in predicting the adverse events and yields of stem cell mobilization.

Granulocyte colony-stimulating factor (G-CSF) is now widely used for stem cell mobilization. We evaluated the role of post-G-CSF white blood cell (WBC) counts and donor factors in predicting adverse events and yields associated with mobilization. WBC counts were determined at baseline, after the third and the fifth dose of G-CSF in 476 healthy donors. Donors with WBC ≥ 50 × 10(3)/µL post the third dose of G-CSF experienced more fatigue, myalgia/arthralgia, and chills, but final post-G-CSF CD34(+) cell counts were similar. Although the final CD34(+) cell count was higher in donors with WBC ≥ 50 × 10(3)/µL post the fifth G-CSF, the incidence of side effects was similar. Females more frequently experienced headache, nausea/anorexia, vomiting, fever, and lower final CD34(+) cell count than did males. Donors with body mass index (BMI) ≥ 25 showed higher incidences of sweat and insomnia as well as higher final CD34(+) cell counts. Donor receiving G-CSF ≥ 10 µg/kg tended to experience bone pain, headache and chills more frequently. Multivariate analysis indicated that female gender is an independent factor predictive of the occurrence of most side effects, except for ECOG > 1 and chills. Higher BMI was also an independent predictor for fatigue, myalgia/arthralgia, and sweat. Higher G-CSF dose was associated with bone pain, while the WBC count post the third G-CSF was associated with fatigue only. In addition, one donor in the study period did not complete the mobilization due to suspected anaphylactoid reaction. Observation for 1 h after the first injection of G-CSF is required to prevent complications from unpredictable side effects.

Flow cytometric scoring system as a diagnostic and prognostic tool in myelodysplastic syndromes.

The aim of this study is to validate the clinical utility of the flow cytometric scoring system (FCSS), quantifying phenotypic aberrancies in the myelomonocytic lineages, in the diagnosis and prognosis for conventionally treated myelodysplastic syndromes (MDS) patients. The bone marrow samples from 56 consecutive newly diagnosed MDS patients were characterized by the FCSS and compared with findings in 27 non-MDS cytopenic patients. The FCSS scores were significantly higher in patients with MDS than those in the non-MDS control. A flow score of 2 or more allowed for a specificity of 100% with 75% sensitivity in distinguishing these two groups. The FCSS scores correlated directly with validated prognostic systems including WHO classification, International Prognostic Scoring System (IPSS), WHO-adjusted prognostic scoring system (WPSS) and transfusion dependency. The median survival of conventionally treated MDS patients was directly related to FCSS group; severe: 6 months; moderate: 19 months and normal/mild: not reached. The multivariate analyses suggested the FCSS risk categories were an independent prognostic factor after adjustment for sex, age (above or below 70 years), IPSS or WPSS risk categories. These results confirm that quantifying aberrancies in the myelomonocytic lineage by FCSS is useful in MDS diagnosis and extends the prognostic utility for conventionally treated/untreated patients, especially among patients classified within the refractory cytopenia with multilineage dysplasia (RCMD) subgroup.

The effect of different harvest strategies on the nucleated cell yields of bone marrow collection.

To improve bone marrow (BM) harvest of the volunteer donors in our institute, we changed from the single-hole needle to the multi-side-hole needle after March 2002, and examined the midway total nucleated cell (TNC) counts during collection after September 2004. The aims of this retrospective study were to evaluate BM harvest yields obtained through different strategies and to examine the correlation between final and midway BM harvests. The distribution of BM harvesting by different strategies was 235 donors with single-hole needles (group A), 389 donors with 5-side-hole needles (group B), and 365 donors with 5-side-hole needles and midway TNC counts (group C). The nucleated cell density of the collected BM was significantly improved by modifying the harvest strategy (0.202 × 10(8)/mL in group A, 0.219 × 10(8)/mL in group B, and 0.250 × 10(8)/mL in group C; P < .001). The percentage of unacceptable TNC dose (<2 × 10(8)/kg) was also decreased in all 3 groups (to 5.9%, 3.6%, and 0%, respectively; P < .001). Multiple regression analysis revealed that donor weight, white blood cell count, and harvest strategy were positively correlated with BM TNC density (P < .001), whereas harvested BM volume was negatively correlated with TNC density (P < .001). On linear regression analysis, highly significant correlations were noted between midway and final TNC densities (r = 0.8774; P < .001) as well as between harvested BM volume and TNC count (r = 0.7937; P < .001). Changing the harvesting needle and checking the midway TNC count improved the harvest outcome.

Correlation between characteristics of unrelated bone marrow donor and cell density of total nucleated cell in bone marrow harvest.

The relationship between the features of bone marrow donor and the quality of marrow harvest has been unclear because most of bone marrow registries have multiple collection centers with somewhat different harvest procedures. We are able to address this issue for Tzu Chi General Hospital is the only collection center affiliated with Tzu Chi Taiwan Bone Marrow Registry. Between November 1997 and March 2002, data of 286 healthy unrelated donors was analyzed to correlate with the cell density of total nucleated cell in bone marrow harvests. The harvest procedure was standardized by single-hole harvest needle under general anesthesia. The operation staffs were restricted within the members of Oncology-Hematology division. The results showed that the cell density of bone marrow harvest was positively correlated with donor body weight and peripheral white blood cell count P = 0.0475, P < 0.0001, but negatively correlated with the total volume of bone marrow harvest P < 0.0001. We recommend that if multiple human leukocyte antigen-matched donors are available, donor with higher body weight and/or higher white blood cell count be selected for allogeneic bone marrow transplantation.

A multiple-center phase II study of biweekly oxaliplatin and tegafur-uracil/leucovorin for chemonaive patients with advanced gastric cancer.

PURPOSE: The current study assessed the efficacy and safety of biweekly oxaliplatin combining oral tegafur-uracil/leucovorin in treating chemonaive patients with advanced gastric cancer. METHODS: Eligible patients were 18-75 years old, had stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0-2. Patients in the current study received 2-h i.v. infusion of oxaliplatin at a dose of 100 mg/m(2) after diluting in 500 mL 5% dextrose/water (dexan premedication), and 5-HT3 antagonist biweekly. Oral tegafur-uracil and leucovorin was given at a dose of 300 mg/m(2)/day and 60 mg/day three times daily from day 1 to 21, respectively, followed by a 1-week rest. Response assessment was based on the RECIST criteria and was performed every two courses. Toxicity was assessed according to NCI common toxicity criteria version 2. RESULTS: From October 2003 to April 2006, 57 patients were evaluated (55 eligible) with a median age of 61 years (range 31-75). According to the assessment of response in 48 evaluable patients, partial response rate was 24/48 (50.0%) (95% CI: 35.23-64.73%) and stable disease was observed in 11 patients (22.92%), and diseased progressed in 13 patients (27.08%). Mean number of oxaliplatin cycles was 3 (0.5-6.5). Median time to progression was 177 days. Median overall survival was 318 days. Major-grade (III/IV) toxicities were diarrhea 25.5%, vomiting 16.5%, anemia 10.9%, numbness 12.7%, thrombocytopenia 7.3%, neutropenia 3.6% and leucopenia 1.8%. CONCLUSIONS: Biweekly, oxaliplatin combining oral tegafur-uracil/leucovorin in treating patients with advanced gastric cancer showed acceptable activity and manageable toxicity.

Factors associated with peripheral blood stem cell yield in volunteer donors mobilized with granulocyte colony-stimulating factors: the impact of donor characteristics and procedural settings.

Peripheral blood stem cells (PBSCs) are increasingly used as the source of hematopoietic stem cells, but there are large variations in harvest outcome between individuals mobilized by granulocyte colony-stimulating factor (G-CSF). We examined the effects of donor characteristics and procedure factors on the day 1 CD34+ cell yield in 373 unrelated healthy donors. G-CSF was administered subcutaneously at a planned dose of 8.3 to 11 microg/kg daily for 5 days, followed by harvest started on day 5 of G-CSF treatment. Of the 373 donors, 159 (42.6%) had the radial artery as the inlet access for harvest. Poor day 1 cell yield was defined as <10x10(6) CD34+ cells/L of processed blood for the first apheresis; 62 donors (16.6%) did not attain this threshold. The male donors had significantly higher yields at harvest compared with the female donors. The female donors had higher CD34+ cell yields if the circulation access was through an artery than if is was through a vein. In a multiple regression analysis, donor age, sex, body mass index (BMI), preharvest white blood cell and circulating immature cell counts, access type, and flow rate correlated with day 1 yield. Female sex, older age, venous access, and a higher flow rate were significantly associated with greater risk for a day 1 poor yield of CD34+ cells (odds ratio=3.0074, 1.045, 4.3362, and 1.1131, respectively). A higher BMI may decrease the risk (odds ratio=0.8472). In donors at higher risk for poor CD34+ cell yield, strategies for increasing CD34+ cells must be considered.

A phase II study of weekly paclitaxel and epirubicin in recurrent or refractory squamous cell carcinoma of the head and neck.

OBJECTIVE: The combination of taxanes and anthracyclines has been proved to be active for treatment of many cancers. We conducted a phase II study to determine the response and toxicity of paclitaxel and epirubicin (TE) in patients with incurable squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with metastatic or recurrent SCCHN and adequate hematologic, renal and hepatic function and a Karnofsky performance status >/=60% were enrolled. Prior chemotherapy and/or radiotherapy were permitted with 4-week interval. The regimen was paclitaxel 60 mg/m(2) and epirubicin 20 mg/m(2), on Days 1, 8 and 15, as an intravenous infusion, repeated every 28 days. Patients with disease progression or unacceptable toxicity were excluded from the study. RESULTS: The current study was intended to treat 43 patients but closed at the planned interim analysis due to early evidence of insufficient efficacy than expectation. Fifteen patients with a median age of 52 years (range, 37-72 years) were accrued. Previously, most patients had received radiotherapy and chemotherapy, and a majority (87%) of patients had treatment-free interval of <6 months. Median Karnofsky performance status was 70% (range, 60-90%). There was one clinical response (7%) and another three (20%) had stable disease. Median overall survival time was 4.5 months. The most common major toxicity was infection (47%), which caused four treatment-related mortalities. Grade 3-4 neutropenia occurred in five patients, but other toxicities were mild and manageable. CONCLUSIONS: In the population with majority of refractory disease of SCCHN, the response rate to TE was lower than expected. Such dose schedule is not recommended unless in chemotherapy naïve patients or in combination with newer agents.

Evolutional change of karyotype with t(8;9)(p22;p24) and HLA-DR immunophenotype in relapsed acute myeloid leukemia.

The rare recurrent translocation of (8;9)(p22;p24) with PCM1-JAK2 fusion was recently characterized in diverse hematological malignancies. Most of them are atypical chronic myeloid leukemia (CML) or other myeloproliferative disorders (MPD), and are predominantly in the male. We report a female patient with acute myeloid leukemia (AML) initially presenting with normal karyotype and negative HLA-DR expression who achieved complete remission after standard chemotherapy. The disease relapsed 7 months later with cytogenetic change of t(8;9)(p22;p24). Flow cytometry analysis showed evolutional change of immunophenotype from negative to positive HLA-DR expression and fluorescence in situ hybridization (FISH) analysis demonstrated a PCM1-JAK2 fusion gene. We speculate that the cytogenetic change of t(8;9)(p22;p24) may induce HLA-DR immunophenotypic switch and a coordination of the two evolutional changes may play a role in leukemic cell progression.