Andrew Jennis

CD34+CD33- cells influence days to engraftment and transfusion requirements in autologous blood stem-cell recipients.

PURPOSE To evaluate the reliability of CD34/CD33 subset enumeration as a predictor of hematopoietic repopulating potential in autologous blood stem-cell transplantation and to determine which patient and treatment-related factors affect the timing, quantity, and type of blood stem cells mobilized. PATIENTS AND METHODS We analyzed blood stem-cell collections from 410 consecutive cancer patients who received mobilization therapy and evaluated factors, including CD34+ subset quantities, that might influence engraftment kinetics and transfusion requirements in autologous blood stem-cell recipients. RESULTS The majority of patients (97%) mobilized CD34+33- cells, which were usually collected in the greatest quantity on the first day of apheresis. Patients who received only growth factor mobilized the highest percentage of CD34+33- cells. Extensive prior chemotherapy limited the collection of CD34+33- cells. In addition to patient diagnosis (P < .006) and total CD34+ cell dose (P = .0001), CD34+33- cell dose (P < .005) and percentage of CD34+33- cells (P < .005) were identified as independent factors significantly predictive of engraftment kinetics. CD34+33- cell dose (R2 < or = .177; P < .0001) was a strong and the only significant predictor of RBC and platelet transfusion requirements. Furthermore, independent of the total CD34+ cell dose, as the CD34+33- cell dose increased, days to neutrophil recovery, days to platelet recovery, and transfusion requirements decreased. CONCLUSION These findings show that CD34+33- cells are readily collected in most cancer patients and significantly influence engraftment kinetics and transfusion requirements in autologous blood stem-cell recipients. CD34+33- cell quantity of the blood stem-cell graft appears to be a more reliable predictor of hematopoietic recovery rates than total CD34+ cell quantity in this setting.

Tumor cell depletion of peripheral blood progenitor cells using positive and positive/negative selection in metastatic breast cancer

BACKGROUND The clinical relevance of tumor cell purging of hematopoietic progenitor cell grafts has yet to be conclusively determined. Therefore, in addition to the demonstration that a method for graft purification is capable of removing an adequate number of tumor cells, it is critical that the procedure has as benign an impact upon the hematopoietic repopulating potential of the graft as possible. We evaluated tumor cell depletion, recovery of CD34(+) cells and post transplant engraftment kinetics as accepted measures of the effectiveness of an immunomagnetic bead (positive and positive/negative) purging methodology. METHODS The patients received either positive selection (CD34 selection alone) or a combination of positive and negative (CD34 selection followed by breast cancer cell depletion) using the Isolex 300 (automated and semiautomated) devices. Immunocytochemistry was used to determine the degree of breast cancer cell contamination before and after the selection procedures to determine the efficacy of the procedure. CD34 enumeration was employed to evaluate the recovery and purity of the CD34-selected cellular products and engraftment indices (days to absolute neutrophil count (ANC) recovery and platelet count (Plt) recovery and transfusion requirements) were evaluated to determine the safety of the procedure. RESULTS A total of 130 aphereses was performed on 101 patients. Ten pairs of collections were pooled before selection to increase the likelihood of achieving CD34 dose goals after selection. In all, 100 positive selections and 20 positive/negative selections were performed. Of the 10 (10.4%) ICC-positive preselection samples, 2 products showed persistent contamination after processing. The majority of patients (85.4%) required one selection procedure to achieve an adequate CD34(+) selected cell dose. Median CD34(+) cell recovery was > 50% for positive selection procedures and > 60% for the positive/negative procedures. The dose of CD34(+) cells infused ranged from 0.76 x 10(6) CD34(+) cells/kg to 27.7 x 106 CD34(+) cells/kg. There were no significant delays in neutrophil or platelet recovery or infections between any of the treatment groups. DISCUSSION CD34 selection alone or in combination with negative selection can result in a significant reduction of contaminating tumor cells in the peripheral blood progenitor cell autograft. Although there was one engraftment failure with the CD34-positive selected cells, transplantation of the selected products after high-dose chemotherapy for metastatic breast cancer did not result in a clinically significant delay in the hematopoietic reconstitutive capacity of the autografts.

Gastric adenocarcinoma: clinicopathologic differences among Hispanics and non-Hispanic whites. A single Institution's experience over 14 years.

Background Gastriccancer is a leading cause of cancer death worldwide and has significant ethnic and socioeconomic differences in distribution. The aim of this study was to compare clinicopathologic characteristics and survival between Hispanics (H) and non-Hispanic whites (NHW) with gastric cancer. Methods We reviewed the records of all patients diagnosed with gastric cancer between 1999 and 2013 at our institution. A total of 638 patients were studied. Demographics, tumor characteristics and survival rate were analyzed. Kaplan-Meier was used for survival analysis. Results There were 101 H and 537 NHW. The median age at diagnosis was 63 years in H and 69 years in NHW. At diagnosis, 48 (48%) of H patients had stage IV disease compared with 195 (36%) of NHW (P<0.03). H were more likely to have distal cancers and poorly differentiated tumors compared to NHW (44% vs. 15%, P<0.0001; 70% vs. 50%, P<0.0002, respectively). There was a significant difference in median overall survival between the two groups, being 51 months for H (95% CI: 34.6-66.9) and 99 months for NHW (95% CI: 77.3-120.7) P<0.0001. In multivariate analysis, age (OR: 1.02, 95% CI: 1.02-1.03, P<0.0001), poor differentiation (OR: 1.21, 95% CI: 1.02-1.43, P<0.02), ethnicity (OR: 1.69, 95% CI: 1.07-2.55, P<0.02), and stage (OR: 1.95, 95% CI: 1.77-2.15, P<0.0001) were independent predictors of survival. Conclusions H patients were diagnosed with gastric cancer at a younger age, to present with advanced disease at diagnosis, and had shorter overall survival compared to NHW.

Clinicopathologic characteristics of early onset colon-rectal cancer: A single center experience.

538 Background: Colorectal cancer (CRC) is the second leading cause of cancer deaths in the U.S. Early recognition of CRC in young patients (pts) is a challenge, and clinicopathologic features at the time of presentation are not well described. The aim of this study was to compare clinico-pathological characteristics and survival between early onset CRC (Age <50) and late onset CRC (Age ≥50). Methods: We reviewed the records of all patients diagnosed with CRC at our institution from 1999 to 2013. Total of 3,066 pts were studied. Demographics, tumor characteristics, and survival rate were analyzed. Patients with polyposis syndromes or genetic predisposition for CRC were excluded. Kaplan-Meier and Cox regression were used for the statistical analysis. Results: Of 3,066 pts, 425 pts (14%) under the age of 50 were identified (28-49). Hispanics (13% vs 8%, p<0.01) and African Americans (7% vs. 4%, p<0.009) were more prevalent in the early onset subgroup (EO) when compared to the late onset subgroup (LO). Pts w...

Intra-glomerular metastases.

Jean Hou, Rosy E. Joseph, Shree G. Sharma, Andrew A. Jennis and Glen S. Markowitz Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, New York, New York, USA and Department of Medicine, Hackensack University Medical Center, Hackensack, New Jersey, USA Correspondence: Shree G. Sharma, Department of Pathology and Cell Biology, Columbia University Medical Center and the New York Presbyterian Hospital, 630 West 168th Street, VC14-238, New York, New York 10032, USA. E-mail: drshreegopal@gmail.com