Tso Fu Wang

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.

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 × 103/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 × 103/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.

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.

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.

Poor harvest of peripheral blood stem cell in donors with microcytic red blood cells

BACKGROUND: The outcome of peripheral blood stem cell (PBSC) harvest depends on mobilization and leukapheresis. Some poor harvests might not be directly related to poor mobilizations.

Multidimensional Flow Cytometry for Detection of Rare Populations in Hematological Malignancies

Abstract Objective Flow cytometry is becoming an important tool in the characterization of different hematological disorders. The aim of our study was to detect very rare populations in hematological malignancies using the comprehensive concept of immunophenotyping. Patients and Methods Six patients, including three with acute myeloid leukemia, one with acute lymphoblastic leukemia, one with myelodysplastic syndrome, and one with B-cell lymphoma, were enrolled in this study. Serial bone marrow aspirates were analyzed by three-color multidimensional flow cytometry. Results The core principles for the use of flow cytometric analysis are understanding deviations in abnormal antigen expression from normal cellular differentiating pathways and characterizing different patterns of antigenic aberrancy for each patient. Our results demonstrate that multidimensional flow cytometry can be used to: (1) monitor minimal residual disease after treatment; (2) aid in the differential diagnosis of cases, which are difficult to evaluate using conventional morphology; and (3) help in the staging of lymphoproliferative disorders. Conclusion After selecting appropriate combinations of monoclonal antibodies, and applying advanced knowledge in immunophenotyping, flow cytometry is very sensitive and specific for the detection of rare populations in hematological disorders.

Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank

To provide information for umbilical cord blood (UCB) banks to adopt optimal collection strategies and to make UCB banks operate efficiently, we investigated the reasons for exclusion of UCB units in a 3‐year recruitment period.

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

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).

Treatment of Metastatic or Recurrent Gastric Cancer with Weekly 24-hour Infusion of Cisplatin and High-Dose 5-Fluorouracil/Leucovorin in an Outpatient Setting

Objective: There is no general agreement over a standard chemotherapy regimen for metastatic or recurrent gastric cancer. We evaluated, retrospectively, the activity and toxicity of weekly 24-hour infusion of cisplatin with high-dose 5-fluorouracil/leucovorin (P-HDFL) in an outpatient setting. Materials and Methods: Patients with metastatic or recurrent gastric cancer, treated in an outpatient setting from May 2001 to July 2005, were analyzed retrospectively. The regimen consisted of continuous infusion cisplatin 25mg/m^2, 5-fluorouracil 2000 mg/m^2 and leucovorin 200mg/m^2 on day 1, 8 and 15 every 4 weeks. The treatment was continued for a maximum of six cycles unless the disease progressed or intolerable toxicities occurred. Results: Twenty-one patients received this regimen: 16 men and 5 women, median age 56 years (range 27-71). A median of 4.3 cycles was administered. Seven of 21 patients (33.3%) achieved an objective partial response. Stable disease was observed in 6 patients (28.6%) and progressive disease in 8 patients (38.1%). The median survival was 7.7 months (95% confidence interval, 6.2-12.8 months). Digestive and hematological toxicities were low and no severe renal insufficiency was observed. The most common toxicity was elevated liver enzymes (11 patients, 52%), of whom three had≥grade 3 toxicity: 1 of them died of hepatic failure. Conclusion: Our results show that outpatient P-HDFL therapy leads to a fairly comparable outcome with various regimens of 5-fluorouracil/cisplatin. This outpatient regimen could be a reasonable alternative that combines advantages in respect of patient activity, mild to moderate toxicity, convenience of dosing and minor expenditure.

Extreme Thrombocytosis in a Patient with Rupturd Colon Cancer and Iron Deficiency Anemia

Extreme thrombocytosis defined as a platelet count exceeding 1000×103/μL was most often thought to be due to clonal myelopro-liferative disorders. Here we report a case of extreme thrombocytosis in a patient with colon cancer who had no evidence of myeloproliferative disorders. This 59-year-old woman presented with abdominal pain and extreme thrombocytosis of 1726×103/μL. Investigations disclosed recto-sigmoid cancer and iron deficiency anemia. Surgical exploration revealed the recto-sigmoid cancer was ruptured with surrounding abscess formation. Bone marrow examination showed no evidence of clonal myeloprolifera-tive disorders. The platelet count returned to the normal range after surgical resection of the primary tumor and resolution of the abscess and the iron deficiency anemia. Eight months later, evidence of progression of multiple liver metastases was found, again accompanied by elevation of the platelet count to 639×103/μL. After successful salvage chemotherapy wit oxaliplatin plus high dose 5-FU and leucovorin, the platelet count returned to normal. We conclude that the combined effects of malignancy, abscess formation and iron deficiency contributed to the extreme thrombocytosis in this case. We suggest that a search for secondary causes is still required for a patient with a platelet count exceeding 1000×103/μL.