Decision letter for "Risk of infectious complications in patients with chronic lymphocytic leukemia in the era of BCR inhibitors: a retrospective single institution experience"

Abstract A retrospective analysis on chronic lymphocytic leukemia (CLL) patients ≤55 years observed at a single institution was performed with the purpose of characterizing the clinical features and outcome of young CLL and of identifying patients with different prognostic features. Over the period from 1984 to 1994, 1,011 CLL patients (204 [20%] ≤55 years of age and 807 [80%] >55 years of age) were observed. At diagnosis, younger and older patients displayed a similar distribution of clinical features, except for a significantly higher male/female ratio in younger patients (2.85 v 1.29;P < .0001). Both groups showed an elevated rate of second primary cancers (8.3% v 10.7%), whereas the occurrence of Richter’s syndrome was significantly higher in younger patients (5.9% v 1.2%; P < .00001). Younger and older patients showed a similar overall median survival probability (10 years) but were characterized by a different distribution of causes of deaths: CLL unrelated deaths and second primary malignancies predominated in the older age group, whereas the direct effects of leukemia were prevalent in the younger age group. Although younger and older patients displayed a similar survival, the evaluation of the relative survival rates showed that the disease had a greater adverse effect on the expected survival probability of the younger population. Multivariate analysis showed that for young CLL patients only dynamic parameters, such as lymphocyte doubling time and other signs of active disease, were the independent factors that significantly influenced survival probability (P = .00001). A prolonged clinico-hematologic follow-up allowed us to identify two subsets of young CLL patients with a different prognostic outcome: a group of patients (40%) with long-lasting stable disease without treatment and an actuarial survival probability of 94% at 12 years from diagnosis and another group (60%) with progressive disease and a median survival probability of 5 years after therapy. For the latter patients, the therapeutic effect of innovative therapies with curative intents needs to be investigated in prospective, comparative clinical trials.

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A phase II pilot study of valproic acid in relapsed/refractory chronic lymphocytic leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.7081 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 7081-7081

Author(s):

P. Ganesan ◽

V. Raina ◽

R. Kumar

Keyword(s):

Valproic Acid ◽

Chronic Lymphocytic Leukemia ◽

Hospital Admissions ◽

Performance Status ◽

Infectious Complications ◽

Significant Rise ◽

Lymphocytic Leukemia ◽

Total Leucocyte Count ◽

Ecog Performance Status ◽

Platelet Counts

7081 Background: Valproic acid (VA) has demonstrated cell-kill by triggering pro-apoptotic pathways in chronic lymphocytic leukemia (CLL) in preclinical studies. We studied the safety and efficacy of VA in patients with relapsed and refractory CLL. Methods: Adult patients with CLL diagnosed by the NCI-WG criteria who had received at least one previous fludarabine-based therapy and subsequently progressed or relapsed with ECOG performance status (PS) ≤3 and normal organ functions were included. Patients were started on VA 10 mg/kg which was gradually increased to 20 mg/kg. Efficacy (NCI-WG criteria) and safety (NCI common toxicity criteria) were assessed at 3 months. Responding patients were continued on the study medication. Results: Five patients have so far been included, age 48–70 years (mean 62 years); sex: 3 males/ 2 females; disease duration: 2–16 years (mean 5.4 years). Previous therapies included fludarabine/alkylators in all patients; in addition rituximab was given in one and lenalidomide in two. Three patients have completed three months of therapy and are evaluable. One patient had partial response and one had stable disease. In the third patient the total leucocyte count continued to rise but there was response in other parameters like decrease in lymphadenopathy by 50%, stabilization of hemoglobin, increase in absolute neutrophil (ANC) and platelet counts. Two of these patients who were requiring 2–3 blood transfusions per month and frequent admissions for infectious complications have not required further transfusions or hospital admissions since starting VA. Significant improvements were also seen in their ECOG PS from 3 to 0–1, 61% and 230 % rise in ANC and 50% and 83% rise in platelet counts. Grade 3 hypersensitivity skin rashes developed in one patient at one month and the therapy was discontinued. Most patients had mild drowsiness and two patients had significant weight gain of grade 2. Conclusions: VA produces very impressive palliation in advanced/ refractory CLL in terms of improvement of hemoglobin, ANC, platelets, PS, and a reduction in the number of infective episodes –apparently a sequel to significant rise in neutrophils. We are encouraged by these results and are continuing the study. No significant financial relationships to disclose.

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Prognosis of chronic lymphocytic leukemia: a multivariate survival analysis of 150 cases

Blood ◽

10.1182/blood.v59.5.1001.bloodjournal5951001 ◽

1982 ◽

Vol 59 (5) ◽

pp. 1001-1005

Author(s):

C Rozman ◽

E Montserrat ◽

E Feliu ◽

A Granena ◽

P Marin ◽

...

Keyword(s):

Survival Analysis ◽

Chronic Lymphocytic Leukemia ◽

Prognostic Value ◽

International Workshop ◽

Risk Groups ◽

Multiple Regression Model ◽

Lymphocytic Leukemia ◽

Multivariate Survival Analysis ◽

Single Institution ◽

Multivariate Survival

A multivariate survival analysis by means of Cox's multiple regression model was performed on a series of 150 consecutive patients with chronic lymphocytic leukemia (CLL) from a single institution. In addition to the well established prognostic factors, such as anemia and thrombocytopenia, a marked prognostic value of the degree of absolute peripheral lymphocytosis emerged from this analysis. This was evident in the whole population as well as in low and intermediate risk groups of patients (Rai's stages 0, I, and II and International Workshop on CLL stages A and B), pointing out that different subsets of patients can be isolated within these groups.

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