Lithium and granulocytopenia during induction therapy of acute myelogenous leukemia

Abstract

Twenty-seven patients receiving a standard cytosine arabinoside and daunorubicin regimen as induction of reinduction therapy of acute myelogenous leukemia were randomly assigned to receive lithium carbonate, 300 mg t.i.d., or no lithium. Treatment groups were comparable with respect to age and baseline granulocyte counts. All patients developed granulocyte nadirs below 100/cu mm. By actuarial analysis, the median duration of granulocytopenia, less than 1000/cu mm, was 16.0 days in the lithium group and 24.6 days in the no-lithium group, p = 0.013. The median duration of granulocytes less than 500/cu mm also favored the lithium group but only approached statistical significance: 14.0 days versus 20.5 days, p = 0.054. Lithium levels between 0.5 and 1.0 meq/liter were easily maintained in 11 of 12 patients receiving lithium, 300 mg t.i.d., and toxicity directly attributable to lithium was not observed. Despite the shortened duration of neutropenia, the incidence of infections and the rate of remission were not affected.

Lithium treatment in adults with acute myeloid leukemia receiving chemotherapy

“…The failure of this study to show a shortening of chemotherapy-induced neutropenia is similar to the result of other reports [7,8], but it differs from the results of studies of lithium treatment in AML patients [5,6] that did show a shortening of neutropenia. Since lithium was not started at the time of biopsy-proven marrow hypoplasia in those studies, and since the duration of neutropenia was not reported from the time of marrow hypoplasia, as it was in our study, a direct comparison of those results with ours is not possible.…”

“…In the treatment of patients with acute myeloid leukemia (AML) infection during chemotherapy-induced neutropenia remains an important problem. Reports have suggested that lithium treatment may lessen chemotherapy-induced neutropenia in patients receiving chemotherapy for nonhematologic malignancy [ 1-31, for acute lymphoblastic leukemia [4j, and for AML [5,6], but preliminary reports of two studies of lithium treatment in AML patients have indicated that lithium failed to shorten chemotherapy-induced neutropenia [7,8]. We have conducted a randomized clinical trial to gather additional evidence concerning the efficacy of oral lithium carbonate in shortening the duration of chemotherapy-induced neutropenia in patients undergoing initial chemotherapy for AML.…”

Lithium stimulates human bone marrow derived mesenchymal stem cell proliferation through GSK‐3β‐dependent β‐catenin/Wnt pathway activation

“…Lithium administration induces leukocytosis [14], resulting in increases in leukocyte and neutrophil numbers. These findings led to the clinical application of lithium for the treatment of granulocytopenia [15] and neutropenia caused by chemotherapy [16,17]. Investigators have proposed that lithium may directly stimulate pluripotent bone marrow stem cells, but no further studies have tested this hypothesis.…”

Increased number of peripheral blood CD34+ cells in lithium‐treated patients

“…The number of CD34 þ cells is not high, but the significant increment in the level of these cells following short-term lithium therapy, and the strong positive correlation with the neutrophil counts, are of clinical importance. Before the era of G-CSF therapy, lithium was given to patients in order to attenuate neutropenia caused by chemotherapy or radiotherapy (Lyman et al, 1980;Stein et al, 1979). This treatment was well tolerated by patients.…”