Acute Lymphoblastic Leukemia News Headlines

Differential in vitro cytotoxicity does not explain increased host toxicities from chemotherapy in Down syndrome acute lymphoblastic leukemia.

Leuk Res. 2008 Aug 19;

Authors: Valle M, Plon SE, Rabin KR

Treatment-related toxicities such as mucositis and infections are both more frequent and more severe in children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) compared to non-DS ALL. Altered methotrexate pharmacodynamics play a role, but severe toxicities also occur in treatment courses that lack methotrexate. We hypothesized that this might be attributable to heightened cytotoxic effects of other ALL chemotherapeutic agents on DS versus non-DS host tissues. Panels of DS and non-DS lymphoblastoid cell lines (LCLs) and primary fibroblast cell lines were treated with asparaginase, dexamethasone, doxorubicin, mafosfamide and vincristine. LCL survival was assessed using the MTT assay, and fibroblast proliferation using the clonogenic survival assay. No significant differences were observed between DS and non-DS cell lines using either assay. Both DS and non-DS cell lines were resistant to dexamethasone at the maximal concentrations tested, and did not differ significantly in sensitivity to the other drugs studied. Thus, heightened in vitro cytotoxicity does not appear to account for the increased treatment-related toxicities observed in patients with DS ALL.

PMID: 18718659 [PubMed - as supplied by publisher]

Cough mixture abuse, folate deficiency and acute lymphoblastic leukemia.

Leuk Res. 2008 Aug 18;

Authors: Au WY, Harod KK, Law MF

We report two young male patients with ALL who were chronic cough mixture abusers. Cough mixture abuse is well known to cause severe folate deficiency, which in turn has been implicated in ALL pathogenesis. Alert for such case association, especially in young male patients with severe dental caries, is warranted. If confirmed, this may pose as a novel leukogenic agent and be a strong deterrent to such emerging substance abuse.

PMID: 18715641 [PubMed - as supplied by publisher]

Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions.

Int J Hematol. 2008 Aug 12;

Authors: Yoshimitsu M, Fujiwara H, Ozaki A, Hamada H, Matsushita K, Arima N, Tei C

A 23-year-old man with Philadelphia-chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his HLA-identical brother in first hematological remission following induction chemotherapy which included imatinib. He had no acute graft-versus-host disease (GVHD), and 4.5 months after HSCT, he had a molecular relapse (180,000 copies/mug RNA of minor bcr/abl transcripts (m-bcr/abl) without mutation in 22 sites including the p-loop region). Following discontinuation of cyclosporine A, imatinib (600 mg daily) was restarted and 4 days later donor lymphocyte infusion (DLI) (5 x 10(7)/kg of CD3(+) cells) was given. In 2 weeks, the marrow m-bcr/abl became undetectable. He received two further DLIs and imatinib was continued at a reduced dose of 400 mg a day. At the time of this report, he remains in complete hematological remission more than 33 months after allo-HSCT and persists in the second molecular remission for longer than 24 months. During this clinical course, he became positive for anti-nuclear antibody after second DLI, without any other manifestations of GVHD. The standard treatment for Ph(+) ALL relapsing after allo-HSCT still remains to be established. Imatinib in combination with DLI for early molecular relapse may be a promising option.

PMID: 18696183 [PubMed - as supplied by publisher]

Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia.

Haematologica. 2008 Aug 12;

Authors: Te Winkel ML, Appel IM, Pieters R, van den Heuvel-Eibrink MM

Coagulation alterations may be involved in osteonecrosis in childhood acute lymphoblastic leukemia. Retrospectively, we evaluated the available coagulation parameters at diagnosis and during induction treatment of 161 acute lymphoblastic leukemia patients: 24 with symptomatic osteonecrosis (median age: 13.8 years, range 4.0-17.2) and 137 without osteonecrosis (median age: 4.9 years, range 1.0-16.7). Coagulation parameters of both groups were similar at diagnosis. After four weeks of treatment including dexamethasone, levels of antithrombin and protein S were significantly less in osteonecrosis-positive than in osteonecrosis-negative patients. Subsequently, after four doses of asparaginase and tapering dexamethasone, these coagulation parameters equally decreased in both groups. Consequently, nadirs of antithrombin and protein S were significantly lower in osteonecrosis-positive than in osteonecrosis-negative patients, even reaching levels below lower normal limits in the osteonecrosis-positive group. A reduced dexamethasone related increase of antithrombin and protein S, and subsequent decline below normal levels after introduction of asparaginase, may result in a hypercoagulable state, contributing to development of symptomatic osteonecrosis.

PMID: 18698082 [PubMed - as supplied by publisher]