Proliferation kinetics of plasma cells and of normal haemopoietic cells in multiple myeloma

Abstract

DNA synthesis time (T,) and 3H thymidine (TdR) labelling index (LI) of bone marrow (BM) myelomatous plasma cells (PC) and of the residual haemopoietic cell population (RHCP) were measured by in vitro quantitative 14C-TdR autoradiography in five patients with multiple myeloma (MM) in different phases of disease (three at presentation and two at relapse) and in one patient with solitary extra-osseous myeloma. One other patient with plasma cell leukaemia (PCL) was studied during an initial relapse phase and later during the leukaemic terminal phase. PC T, was 18.8 & 3-7 (from 13-3 to 25.0) hr and PC LI was 2.5 4 1.8% (from 1.0 to 6.3%). In the case of PCL, circulating PC had a T,of 14-4 hr and a LI of 3.1. From these experimental measurements, the fractional turnover rate (FTR-percentage of cells produced per unit time) and the potential doubling time (TJ of BMPC were calculated assuming that all BMPC were in a steady-state at the time of the study. BMPC FTR was 3.53 & 2.3% cells per day (from 1.2 to 6-72) and BMPC Td was 46.8 & 27.5 days (from 15.0 to 75.4). Comparison with results obtained in BM blasts of children with acute lymphoblastic leukaemia (ALL) indicated that BMPC had a lower proliferative activity (P < O.OOl), although BMPC T, was not significantly different. In two patients a tumour doubling time of 6 and 13 months was determined by clinical follow up. Comparison of this parameter with Td showed a cell loss factor of more than 90% in both patients.Kinetic data relative to RHCP showed slight variations with respect to those found in normal subjects, with a general tendency towards a prolongation of T, and a reduction of LI. Kinetic studies in multiple myeloma (MM) usually deal with the labelling index (LI) of neoplastic plasma cells, which has been shown to be of prognostic significance (Durie, Salmon& Moon, 1980; Greipp & Kyle, 1983; Latreille et al., 1982; Riccardi et al., 1986). Other kinetic parameters, such as DNA synthesis time (TS), are difficult to obtain. The proliferative activity of the tumour population is, in fact, low and therefore hampers the application of the classic, timeconsuming techniques used for detailed cell kinetic investigations, such as the labelied mitoses method and the double labelling technique, which further require multiple bone marrow (BM) cell sampling.

Isatuximab monotherapy in patients with refractory T‐acute lymphoblastic leukemia or T‐lymphoblastic lymphoma: Phase 2 study

“…Given the uniform nature of the expression of CD38 in T‐ALL and T‐LBL patients, it is feasible that isatuximab could be efficacious in patients with less advanced disease or if used in conjunction with chemotherapy or other targeted therapies, as is the case when isatuximab is used in conjunction with pomalidomide and dexamethasone in MM. Differences in blast cell kinetics and disease burden between MM and ALL may also account for the lack of efficacy of isatuximab monotherapy in relapsed or refractory ALL compared with MM 15 . A further consideration is that the median duration of isatuximab therapy in the study was 3.5 weeks, which may not have been sufficient time to achieve an optimal response.…”

“…The primary endpoint was to assess the efficacy of isatuximab by overall response rate (ORR). Secondary endpoints included duration of response, 15 progression‐free survival, immunogenicity of isatuximab in patients with T‐ALL/T‐LBL, minimal residual disease, and the safety profile of isatuximab. Overall, 16 patients were screened but two patients failed screening (one patient had an ongoing unspecified infection and one patient did not have relapsed or refractory T‐ALL/T‐LBL).…”

Prognostic significance of the S-phase fraction of light-chain-restricted cytoplasmic immunoglobulin (cIg) positive plasma cells in patients with newly diagnosed multiple myeloma enrolled on eastern cooperative oncology group treatment trial E9486

“…This is because high S-phase normal hematopoietic cells contaminate and cause false elevation of the S-phase % measurement of the slowly proliferating malignant plasma cells. Measuring the S-phase fraction of solid tumors, breast, prostate, and colon cancer is less of a problem because the S-phase fraction in the contaminating normal cells is relatively low [22,32].…”

Proliferative activity of myeloma cells determined by Ki-67 antibody: Biological and clinical significance

“…Najčešće korišćena metoda za određivanje proliferativne aktivnosti kod MM je metoda autoradiografije. U više studija je pokazano da kinetika ćelijske proliferacije merena metodom autoradiografije (proliferativni indeks) ima prognostički značaj kod bolesnika sa multiplim mijelomom (1,11,12). Međutim, i pored toga ova metoda nije našla svoje mesto u rutinskoj kliničkoj praksi zbog komplikovanosti i vremena potrebnog za njeno izvođenje.…”