Survivals of two series of CLL patients (99 from a retrospective series and 196 from a prospective series) were studied separately The three main staging systems (Rai, Binet, Rundles) agreed well, but as far as survival is concerned, too many stages are defined The authors performed a Cox multivariate analysis of survival in order to isolate important prognostic factors at diagnosis and to use them to build a simple three-stage classification Thrombopenia and anemia appeared as the most important risk factors Among the nonanemic and nonthrombopenic patients, the number of involved areas was clearly related to prognosis in the authors' two series This study allowed the authors to propose a new classification in three prognostic groups Group C: anemia (Hb less than 10 g) and/or thrombopenia (platelets less than 100,000/mm3); about 15% of the patients; median of 2 years Group B: no anemia, no thrombopenia, three or more involved areas (counting as one each of the following: axillary, cervical, inguinal, lymph nodes, whether unilateral or bilateral, spleen and liver); about 30% of patients; median of 7 years Group A: no anemia, no thrombopenia, less than three involved areas; about 55% of patients; the survival of this group does not seem different from that of the French population of the same age and sex distribution This three-stage classification only requires clinical examination and routine hemogram, has a good prognostic value which was confirmed on the series of Montserrat and Rozman (146 patients), and should therefore be helpful in planning new clinical trials

A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis.

Classification of Non-Hodgkin’s Lymphomas

One hundred and twenty-nine patients with chronic lymphocytic leukemia (CLL) followed in our outpatient department for periods ranging from 6 months to 13 years were divided into five anatomico-clinical stages: stage O (peripheral and bone marrow lymphocytosis); stage I (stage O + lymph node enlargement); stage II (stage O + palpable spleen); stage III (stage I + II); and stage IV (anemia or thrombocytopenia). Analysis of actuarial survival curves revealed the following: 1) median survival of the entire population exceeded 114 months; 2) there was no difference between the curves of stage O and stage I patients, 3) there was a significant difference between survival for stage III and IV patients as compared with stages O, I and II (p < 0.01); and 4) median survival for stage III and stage IV was 70 months; and 23 months, respectively. Age did not appear to be a prognostic factor. Prognosis was poorer in male patients and in those with a high initial lymphocyte count (50,000/mm3), but this was due to the higher incidence of stages III and IV in this population (p < 0.01). It was not possible, from this study, to draw any conclusions as to the beneficial effect of chlorambucil in the treatment of this disease. However, in patients treated with chlorambucil the response to therapy appeared to be a factor of prognostic significance. Patients who showed clinical and hematologic remission had a better prognostic outlook than those who showed only a partial response, while the worst prognosis was encountered in patients who did not respond at all. The five-stage anatomico-clinical classification system suggested appears to be the dominant prognostic factor and may thus serve as a guideline for therapeutic strategy. Cancer 40:855–864, 1977.

A clinical staging system for chronic lymphocytic leukemia. Prognostic significance

Bone marrow histologic pattern--the best single prognostic parameter in chronic lymphocytic leukemia: a multivariate survival analysis of 329 cases.

Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis.

From a study of the pretreatment bone marrow biopsy and absolute peripheral blood lymphocyte count, we found that a reasonably accurate prognosis for patients with early CLL could be made. The ratio of percentage bone marrow space occupied by lymphatic tissue in sections of the first pretreatment bone marrow biopsy to the absolute peripheral blood lymphocyte count at that time was found to be inversely proportional to survival time (p <.01). Other indications of poor prognosis were diffuse rather than nodular lymphatic infiltration, lymphoblasts rather than small lymphocytes, and increased numbers of bone marrow plasma cells.

Bone marrow and peripheral blood lym‐phocytosis in the prognosis of chronic lymphocytic leukemia

Bacterial enzymes: powerful tools for protein labeling, cell signaling, and therapeutic discovery.

In this issue of Cell Chemical Biology, Zhan et al. report dual-pharmacophore molecules (“artezomibs”), combining an artemisinin and proteasome inhibitor that exhibit potent activity against both wild-type and drug-resistant malarial parasites. 1 Zhan W. Li D. Subramanyaswamy S.B. Liu Y.J. Yang C. Zhang H. Harris J.C. Wang R. Zhu S. Rocha H. et al. Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin- proteasome system to kill malaria parasites and overcome resistance. Cell Chem Biol. 2023; 30https://doi.org/10.1016/j.chembiol.2023.04.006 Abstract Full Text Full Text PDF Google Scholar This study indicates that artezomibs offer a promising approach to combat drug resistance encountered by current antimalarial therapies. In this issue of Cell Chemical Biology, Zhan et al. report dual-pharmacophore molecules (“artezomibs”), combining an artemisinin and proteasome inhibitor that exhibit potent activity against both wild-type and drug-resistant malarial parasites. 1 Zhan W. Li D. Subramanyaswamy S.B. Liu Y.J. Yang C. Zhang H. Harris J.C. Wang R. Zhu S. Rocha H. et al. Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin- proteasome system to kill malaria parasites and overcome resistance. Cell Chem Biol. 2023; 30https://doi.org/10.1016/j.chembiol.2023.04.006 Abstract Full Text Full Text PDF Google Scholar This study indicates that artezomibs offer a promising approach to combat drug resistance encountered by current antimalarial therapies. Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin-proteasome system to kill malaria parasites while overcoming drug resistanceZhan et al.Cell Chemical BiologyMay 5, 2023In BriefZhan et al. combined two anti-malarial agents—an artemisinin and a proteasome inhibitor—into a single compound called ATZ, which has an additional anti-malarial mechanism of action beyond that of its components. ATZ killed malaria resistant to either component or both. Full-Text PDF 

Jan L. Gray

Papers

Bone marrow and peripheral blood lym‐phocytosis in the prognosis of chronic lymphocytic leukemia

Bacterial enzymes: powerful tools for protein labeling, cell signaling, and therapeutic discovery.

Weaponizing the proteasome to overcome antimalarial drug resistance.