Measurements were performed in 143 patients with monoclonal gammopathy of the cellular substrate in the bone marrow. including analysis of DNA and RNA content and tritiated thymidine labeling index. Aneuploidy by DNA content was present in 80% of I 1 5 patients with active multiple myeloma and in 4 of 9 patients with benign monoclonal gammopathy. but was absent in all 1 2 patients with myeloma in remission and in 7 individuals with Waldenstr#{246}m’s macroglobulinemia. With regard to prognosis in multiple myeloma. a low pretreatment plasma cell

The cytotoxicity of the investigational anticancer drugs fluoro-ara-AMP, homoharringtonine, and elliptinium on normal human granulocyte-macrophage colony-forming units in culture (GM-CFU) was investigated using a bilayer soft agar system. For each drug, the dose-dependent survival curve on a semilogarithmic plot formed a straight line. The Do were: 0.51 μg/ml (fluoro-ara-AMP), 0.004 μg/ml (homoharringtonine) and 0.026 μg/ml (elliptinium). The in vitro toxicity of drugs on bone marrow progenitor cells did not correlate with the relative myelosuppressive potency observed in vivo.

The lethal effects of cis-dichlorodiammineplatinum(ll) were investigated on an established human colon carci noma cell line. cis-Dichlomodiammineplatinum(ll) was one of the most efficient antineoplastic agents tested thus far on this human colon carcinoma cell line. Survival of expo nentially growing cells exposed to increasing concentra tions of the drug (both in medium or in Hanks' balanced salt solution) was of the threshold exponential type (D@ 1.2 @g/ml,1 hr; D0 = 3.5 @g/ml,1 hr). Stationary-phase cells were extremely sensitive to the drug, and the survival curve demonstrated a simple exponential pattern (D0 = 3.9 j.tg/ml, 1 hr). Long-term exposure to low concentrations of cis-dichlorodiammineplatinum induced a high degree of killing, with only 0.5% of the cells surviving after incubation for 24 hr with 2 @tg/ml.Cells were unable to recover from potentially lethal or sublethal damages induced by the drug.

Abstract. To investigate the effect of donation time on the quality of blood components, we measured the platelet count and pH on platelet concentrates, and the factor V and VIII: C levels and fibrinopeptide A concentration on fresh‐frozen plasma by duration of donation time. Platelet concentrates and fresh‐frozen plasma were classified into three groups according to donation time: group 1, less than 10 min; group 2, 10–15 min, and group 3, longer than 15 min. Mean platelet counts of platelet concentrate were: group 1, 8.6±2.5 (in x 1010), group 2, 8.1±2.6, and group 3, 6.5±3.2 (p<0.05). The same pH was maintained in all three groups. The fibrinopeptide A concentrations in groups 1 and 2 were 24±53 and 169±64 ng/ml, respectively, while in group 3 all were >200 ng/ml, indicating correlation of a higher fibrinopeptide A level with longer donation time. Although a higher fibrinopeptide A level indicated a greater degree of thrombin generation, assays of factors V and VIII: C did not show decreased activity in groups 2 and 3.

Six colon cancer cell lines segregated into three groups with distinct biological properties (i.e., morphological differentiation, DNA content, carcinoembryonic antigen production, etc.) were treated with ten antitumor drugs. Cytotoxic responses were heterogenous and not associated to biological grouping, in fact, for some drugs, the response of one member of the group resembled that of a member of another group rather than its group counterpart. Thus the most common phenotypic characteristics that identify colon cancer cells did not predict the cytotoxic response and do not appear useful for stratifying patients into categories with distinct responses to currently available chemotherapeutic agents.

The role of liposome entrapment in modulating the cytotoxicity of a lipophilic cisplatin derivative was assessed. cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum++ +(II) (NDDP) was tested in suspension (free NDDP) or entrapped in multilamellar vesicles composed of dimyristoylphosphatidyl choline and dimyristoylphosphatidyl glycerol (L-NDDP). Against LoVo colon carcinoma cells sensitive to cisplatin, L-NDDP was two times more cytotoxic in vitro than free NDDP and cisplatin (Do 7 microM for L-NDDP, 15 microM for free NDDP, and 16 microM for cisplatin). Against LoVo cells resistant to a concentration of 3 micrograms/ml of cisplatin, L-NDDP was three times more cytotoxic than free NDDP and cisplatin (Do 14 microM for L-NDDP, 45 microM for free NDDP, and 48 microM for cisplatin). In in vivo studies, free NDDP was less potent and less active than L-NDDP against i.p. L-1210 leukemia (free NDDP, optimum %T/C 148 at a dose of 75 mg/kg; L-NDDP, optimum %T/C 185 at a dose of 25 mg/kg) and i.p. L1210/PDD leukemia (free NDDP, optimum %T/C 128 at a dose of 50 mg/kg on Days 1, 5, and 9; L-NDDP, optimum %T/C 200 at a dose of 12.5 mg/kg on Days 1, 5, and 9). Free NDDP administered i.v. was inactive against liver metastases of M5076 reticulosarcoma (%T/C 102) while L-NDDP showed significant activity (%T/C 140). The single dose i.v. LD50 in mice of free NDDP and L-NDDP were similar (79.4 mg/kg for free NDDP and 64.5 mg/kg for L-NDDP). These studies show that NDDP is a liposome-dependent drug since it can only be satisfactorily formulated in the liposomal form and since the liposomal carrier plays a crucial role in determining its antitumor activity.

Peripheral blood samples from 48 untreated and 20 treated patients with disease entities that directly or indirectly affect hematopoiesis [dys-myelopoietic syndrome (DMS), refractory anemia with excess blasts (RAEB) or in transformation (RAEBIT), lymphoma, myeloma, acquired immunodeficiency syndrome (AIDS), and solid tumors with uninvolved bone marrow] were measured with the Technicon H-6000 automated hematology analyzer; this instrument provides a differential count on 10(4) white blood cells (WBC) effected by means of flow cytochemistry (peroxidase content) and volume (light scatter) discrimination. Cases with DMS and RAEB showed statistically significantly lower WBC counts than normal, whereas cases with lymphoma showed significantly higher values. No disease entity demonstrated changes in mean peroxidase activity (MPA) that were significantly different from normal, although all disease entities, including cases with solid tumors, showed significantly higher (two to severalfold) proportions of cells with high peroxidase (HPX) content, probably as a reflection of a disturbance of normal hemopoiesis with the emergence of younger granulocytic forms. All cases with paraleukemia (DMS, RAEB, and RAEBIT) showed significantly higher values of large unstained cells (LUC), whereas cases with lymphoma showed significantly lower LUC values. There were no statistically significant differences for any parameter (WBC counts, MPA, HPX, or LUC) among the paraleukemia subtypes. However, based on the displayed trends, a case presenting with dyserythropoiesis, relatively low WBC counts, abnormal HPX values, and LUC below 10% should be suspected for RAEB, whereas the presence of greater than 10% LUC and almost normal or even slightly elevated WBC counts should suggest a more accelerated phase of RAEB. Unless complicated by a leukemic phase, cases of lymphoma or myeloma did not display changes in any of the parameters analyzed by the H-6000. Similarly, patients with AIDS had no overt changes other than a trend to lower WBC counts with occasionally higher or lower absolute lymphocyte counts than normal. The peripheral blood of patients with solid tumors displayed a slight increase in HPX, suggesting an indirect effect on hemopoiesis since careful workup failed to demonstrate bone marrow involvement. Our data demonstrates that an H-6000 analysis has a role in the evaluation and follow-up of all these entities particularly to document leukemic transformation of either lymphoma, myeloma, or RAEB.

The performance of the Ortho ELT-15 hematology analyzer was evaluated in the high volume, computerized clinical hematology laboratory at M.D. Anderson Hospital and Tumor Institute, Houston, and compared with that of reference instrumentation currently in use for routine patient care, the Coulter S-Plus II. The within-run precision, linearity, and lack of carryover was excellent, and the day-to-day precision was acceptable for the entire range of tested parameters. Coefficients of correlation for these parameters were 0.99 or greater, with the exception of the mean corpuscular volume, where r = 0.95. Special emphasis was placed on the correlation study of white blood cells and platelets at low ranges. Correlation was extremely good (r = 0.97) for white blood cell counts less than 4.0 x 109 L (4.0 x 103/ μL) as well as for PLT counts (r = 0.93) less than 50 x 109/L (50 x 103/μL). These excellent performance characteristics for the complete blood cell parameters make the ELT-15 another superior advance over previous instrumentation in the field of automated hematology.

Transferrin is an iron-carrying compound that stimulates cell growth and division by binding to specific receptors (TR) which are preferentially expressed by actively growing cells or by the malignant counterpart of normal cells. However, quiescent cells may not necessarily cease expressing TR. We evaluated TR expression by flow cytometric analysis utilizing a monoclonal antibody (OKT-9) specific for TR on six established human colon cancer cell lines with distinct degrees of phenotypic differentiation and growth rates at sequential stages of in vitro growth (exponential and stationary phase). There were no significant differences in the proportion of cells expressing TR among the fast and slow growing cell lines at any time point of the study, nor did the cultures change the proportion of TR positive cells in their transit from exponential into stationary phase of growth. Hence, direct measurements of TR expression in malignant cell populations may not provide a useful clinical marker to distinguish highly proliferative tumors from those with a slower growth resulting from a larger proportion of quiescent cells.

Summary Peripheral blood samples from 73 patients with chronic leukaemia were measured with the Technicon H‐6000 automated haematology analyser to provide flow cytochemical (peroxidase content) and volume (light scatter) discriminated scattergram patterns. For chronic granulocytic leukaemia (CGL). these patterns were so reproducible and distinct that they allowed an immediate diagnosis even without the benefit of microscopic examination, Relative and absolute basophilia was an invariable feature, and remained detected by the H‐6000 even when the patient was in haematologic and cytogenetic remission or progressed into blast crisis (BC). Meet patients in BC also demonstrated an inordinately high number oflarge unstained cells (LUC) and high proportions of ‘lymphocytes’(small blasts with no peroxidase content by visual inspection). Thus, for patients with CGL, LUC values above 10%, and/or steady increments in the proportion of ‘lymphocytes’, merit concern as these changes may herald an accelerated phase of disease.The scattergram pattern of untreated chronic lymphocytic leukaemia (CLL) showed a dense accumulation of data points within the lymphocytic ‘box’with a small cluster of granulocytic elements. Most patients also had a frankly abnormal proportion of LUC. Sixteen patients with CLL were compared for ratios of LUC to lymphocytes and stage of disease; patients with the most advanced stage (IV) had the highest, statistically significant values, than the patients with more benign disease. Thus, it is possible that follow up with this instrument of patients with CLL will also allow early detection of an impending prolymphocytoid transformation (accelerated phase) of this disease.

Sixty-four separate intracranial inoculations of bone marrow cells obtained from 26 patients with human myeloma were performed and the animals were kept under observation for 9-10 months. Samples were obtained from a heterogenous group of patients with diverse types of paraprotein production, clinical status, and response to treatment. Inocula size ranged from 3.5 x 10(5) nucleated cells to about 2 x 10(7), while the percentage of plasma cells varied from nondetectable to 90%. Only one animal (of 2) injected with an aliquot of the bone marrow aspirate from a patient developed a small, clinically undetectable tumor, noticed at the end of the observation period. No other animal developed tumors. Thus, our studies indicate that the intracerebral inoculation of human myeloma cells may not be a profitable means of establishing additional human myeloma cell lines.

We conducted an evaluation of the hemostatic integrity of patients with untreated cancer of the prostate. Of 60 patients analyzed retrospectively, only 1 had a mild case of disseminated intravascular coagulation, possibly associated with concomitant estrogen therapy, and in 1 patient mild deep vein thrombosis developed preoperatively, also possibly associated with multiple medications for concurrent disorders. Of 16 other patients prospectively evaluated on admission, only 1 had frankly abnormal levels of fibrinopeptide A unaccompanied by other coagulation abnormalities. Occasional individuals had minimal, negligible deviations of partial thromboplastin times, thrombin time, or antithrombin III values. In none of these patients did hemostatic complications develop during their hospital stay. These results demonstrate that although an occasional coagulation abnormality may occur in patients with cancer of the prostate (albeit with a lower incidence than in other neoplasms), this malignancy does not require increased precautions with respect to those given to the patient population at large.

The performance of the Technicon H*1 was evaluated in the computerized, high-volume hematology laboratory at M.D. Anderson Hospital and Tumor Institute and compared with that of reference instrumentation used for routine patient care. The precision, linearity, and lack of carry-over of this instrument was excellent for the entire dynamic range of all nine tested parameters (white blood cells [WBCs], red blood cells [RBCs], hemoglobin [Hgb], hematocrit [Hct], mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], red blood cell distribution width [RDW], and platelets [Plts]). Coefficients of correlation for all directly measured parameters were always 0.98 or greater, with the exception of the MCV and RDW parameters, for which r = 0.89 and 0.93, respectively. Special emphasis was placed on WBC and Plt counts at low ranges. When compared with reference methods the correlation for both parameters was very good, r = 0.99 for WBCs less than 4.0 X 10(3)/microL (4.0 X 10(9)/L) and 0.91 for Plt less than 100 X 10(3)/microL (100 X 10(9)/L). These excellent performance characteristics for the CBC parameters, combined with the ability of the analyzer to perform a full WBC differential (to be described in the next report), make the H*1 a superior advancement in the field of automated hematology.

SummaryPeripheral blood samples from 118 patients with acute leukaemia (68 untreated; 50 treated) were measured with the Technicon H‐6000 automated haematology analyser. This instrument provides, in addition to measurements of the classical haematology parameters (i.e. cell counts, haemoglobin concentration, etc.), a differential count on 104 WBC effected by means of flow cytochemistry (peroxidase content) and volume (light scatter) discrimination. Disregarding RBC and platelet counts and their volume distribution profiles, the most important diagnostic parameters for leukaemic disease were the WBC count, the WBC differential count, and the proportions of large unstained cells (LUC) and high peroxidase (HPX) cells obtained by the automated differential count as well as the mean value of the WBC peroxidase content distribution (MPA). Granulocytic leukaemias had lower MPA than normal and lymphocytic leukaemias had MPA values above normal. M1 leukaemias were also characterized by large proportions of LUC and low fractions of HPX, while M2 leukaemias showed low LUC with high HPX. M3 leukaemias had low LUC and very high HPX. M4 leukaemias had large LUC and‘monocytic’components and a modest fraction of HPX. M5 leukaemias had very large numbers of LUC,‘monocytes’and‘lymphocytes’and a normal HPX. For M1 leukaemia, the presence of less than 7% LUC following induction treatment was related to morphological changes of normal cells induced by chemotherapy while LUC above 10% usually indicated unsuccessful induction associated with the presence of residual blasts. If treatment was successful, M2 and M3 leukaemias characteristically decreased their HPX population. All M4 leukaemias studied by us failed to enter remission and continued to display high proportions of HPX and LUC. Similarly, most M5 leukaemias had a poor response to treatment and always showed a very high proportion of LUC. Untreated lymphocytic leukaemias demonstrated high LUC, normal HPX and a high proportion of‘lymphocytes’. Hairy cell leukaemias showed almost equal proportions of‘lymphocytes’and LUC. Successful chemotherapy of all lymphoid leukaemia entities was associated with rapid decreases in LUC. slower decrements of‘lymphocytes’and moderate and transient increments in HPX. Thus, flow cytochemistry can assist not only in the segregation of acute leukaemias along with FAB classification with nonmorphologic criteria, but also in the follow up of patients with these diseases.

The Author’s Reply: Thanks, Appreciation, and Celebration Get access Benjamin Drewinko, M.D., Ph.D. Benjamin Drewinko, M.D., Ph.D. Professor and Chief Section of Laboratory Hematology Division of Laboratory Medicine M.D. Anderson Hospital Houston, Texas Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 87, Issue 6, 1 June 1987, Page 790, https://doi.org/10.1093/ajcp/87.6.790 Published: 01 June 1987

Less than Full Get access David Bessman, M.D. David Bessman, M.D. Department of Medicine Division of Hematology/Oncology The University of Texas Medical Branch at Galveston Galveston, Texas Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 87, Issue 6, 1 June 1987, Pages 789–790, https://doi.org/10.1093/ajcp/87.6.789a Published: 01 June 1987

The performance of the Technicon H-6000 was evaluated in the computerized, high-volume hematology laboratory at M.D. Anderson Hospital and Tumor Institute, Houston, Tex, and compared with that of reference instrumentation used for routine patient care. The within-run precision, linearity, and lack of carryover was excellent, and the day-to-day precision was satisfactory for the entire range of tested parameters (WBC, RBC, HGB, HCT, MCV, RDW, and PLT). Coefficients of correlation for these parameters were 0.98 or greater, with the exception of the MCV (r = 0.93). Special emphasis was placed on the correlation study of WBCs and PLTs at low ranges. Correlationwas very good (r = 0.98) for WBC counts below 4.0×103/μL (4.0×109/L) but poor (r = 0.52) for PLT counts less than 50×103/μL (50×109/L). These findings prompted a program change in the analytical algorithm for PLT counts by Technicon Instruments Corp. After this change, an excellent correlation coefficient (r = 0.91) was demonstrated for PLT counts in the low range.