John B. Harley

Comparative study of cytosine arabinoside therapy alone and combined with thioguanine, mercaptopurine, or daunorubicin in acute myelocytic leukemia.

Three hundred twenty‐six patients with acute myelocytic leukemia were randomly and prospectively assigned to four therapeutic regimens: cytosine arabinoside either alone or in combination with daunorubicin, 6‐mercaptopurine, or 6‐thioguanine. The results in 231 qualified previously untreated patients were analyzed. The combination treatments produced a significantly greater frequency of complete or partial remission than single drug therapy. Treatment with cytosine arabinoside and thioguanine led to 48% ageadjusted complete and partial responses. The median survival from diagnosis of all 66 evaluable patients treated with these two drugs was 18 weeks, while the median survival for those who responded to this combination was 15 months.

A comparative study of a bcnu containing 4-drug program versus mopp versus 3-drug combinations in advanced Hodgkin's disease. A cooperative study by the cancer and leukemia group B

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkins disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3‐drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4‐drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3‐drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4‐drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

Thymoma, plasma cell myeloma, red cell aplasia and malabsorption syndrome

Abstract Described herein is a sixty-nine year old woman who had a thymoma associated with a multitude of immunologic deficiency diseases including pure red cell aplasia, multiple myeloma, malabsorption syndrome and the presence of antimuscle antibodies. This appears to be the first case in which a complete spectrum of immunologic deficiency diseases has occurred and thus has provided an opportunity to analyze the therapeutic response and to speculate on the possible mechanisms involved.

Abstract LB-137: A new clinical-grade MEMS-based cell sorter for adoptive T-cell therapy

For advanced, refractory malignancies, adoptive T cell therapy represents an increasingly attractive modality with the potential for significant anti-tumor efficacy, minimal toxicity and longterm immunoprotection. This approach involves the ex vivo isolation and expansion of a patient9s tumor-reactive T cells. Such T cells are rare, and difficult to isolate. Iterative cycles of in vitro re-stimulation, limiting dilution cloning and screening of hundreds to thousands of T cell colonies are required to select for a tumor-reactive population of T cells. Although remarkable responses have been achieved, the time and resource intensive nature of this process has limit the use of adoptive T cell therapy to a handful of centers with specialized facilities and personnel. A closed-system clinical-grade cell sorter that provides a high-speed, sterile and multi-parametric system for isolating low frequency antigen specific T-cells in a cost-effective, easy-to-use and high performance manner would be desirable. A personal-sized cell sorter was developed which uses classical Fluorescence Activated Cell Sorter (FACS) laser excitation and fluorescence emission for interrogation and identification of cells; however, the laser excitation and detection regions, sorting actuator, sample reservoirs, and all of the fluidic channels are contained in a single, closed, disposable, low cost cartridge. The heart of the sorting cartridge is the MEMS microchip which is the world9s fastest valve which can open and close in about 15-20 usec allowing a sort rate of more than 100 million cells/hour Cell Sorting of Human Antigen-specific CD8 T cells We determined the lowest threshold limit for MEMS-based antigen-specific T cell single color sorting using fluorescent-conjugated peptide-MHC multimers using a panel of well-characterized tumor-associated antigen (TAA)-specific T cell clones established in our lab were titrated o autologous PBMCs. We demonstrate discrete recognition of the antigen-specific population and the ability to routinely achieve a sort purity of > 85%, yield of > 90% and viability of > 95% starting from a T cell frequency of 85% with preserved functionality, enhanced viability over conventional stream in air sorters (where cells are subject to 10-50 fold greater shear forces), and expansion capacity after sort to >2000 fold reducing time to treatment for patients from 84 to 24 days. The use of a completely self-contained, disposable cartridge system provides substantial cost savings and allows for multiple samples to be run by a single operator. Development of multicolor and tandem sorting to facilitate enrichment of large volume samples is being pursued. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-137. doi:1538-7445.AM2012-LB-137