Secondary Ph+ acute lymphoblastic leukemia after temozolomide

Vita, Serena De; Matteis, Silvia De; Laurenti, Luca; Chiusolo, Patrizia; Reddiconto, Giovanni; Fiorini, Alessia; Leone, Giuseppe; Sica, Simona

doi:10.1007/s00277-005-1093-6

Cited by 45 publications

(26 citation statements)

References 6 publications

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“…A second step that must occur prior to activation is the dissociation of the b-subunits of factor XIII. 7 The paper by Siebenlist et al 1 measured the first step in factor XIII activation, activation peptide cleavage, whereas our paper measured the last step in factor XIII activation, the expression of catalytic activity. Our hypothesis is that ␥ A /␥Ј fibrin(ogen), by virtue of its binding to factor XIIIbsubunits through the ␥Ј chain, 4 increases the rate of factor XIII activation by increasing the rate of factor XIIIb-subunit dissociation from the catalytic aЈ-subunits.…”

Section: To the Editormentioning

confidence: 71%

“…6 Despite initial hopes that TMZ would be less leukemogenic than traditional alkylating agents, 2 groups have recently reported secondary myeloid malignancies after TMZ treatment in clinical studies. 7,8 As TMZ moves into the front line of our chemotherapeutic armamentarium, further investigation of its in vivo mutagenic potential is warranted.…”

Section: Mutagenic Potential Of Temozolomide In Bone Marrow Cells In mentioning

confidence: 99%

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Mutagenic potential of temozolomide in bone marrow cells in vivo

Geiger

Schleimer

Nattamai

et al. 2006

Blood

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Section: To the Editormentioning

confidence: 71%

Section: Mutagenic Potential Of Temozolomide In Bone Marrow Cells In mentioning

confidence: 99%

Mutagenic potential of temozolomide in bone marrow cells in vivo

Geiger

Schleimer

Nattamai

et al. 2006

Blood

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“…The other patient was diagnosed with oligodendroglioma and was treated with TMZ-based adjuvant chemotherapy. Bone marrow cytogenetics revealed chromosome abnormalities in 2 cases: 1 with t(4;11)(q21;q23) (14), and the other with breakpoint cluster region/Abelson murine leukemia rearrangement, t(9;22) and monosomy 7 (13). During concurrent chemoradiation, TMZ was administered orally at 75 mg/m 2 /d 5 consecutive days a week for 42 days.…”

Section: Discussionmentioning

confidence: 99%

“…A review of the existing literature demonstrated that only 7 cases of TMZ-related acute lymphoblastic leukemia (ALL) have been reported thus far (13)(14)(15)(16)(17)(18). The current case describes an 11-year-old boy with glioblastoma multiforme, who developed B-cell ALL 6 months after the last dose of TMZ.…”

Section: Introductionmentioning

confidence: 94%

Acute lymphoblastic leukemia following temozolomide treatment in a patient with glioblastoma: A case report and review of the literature

Liu

Lei

et al. 2018

Oncol Lett

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Abstract. Temozolomide (TMZ) is a second-generation oral alkylating agent that functions against a number of central nervous system neoplasms, and is generally used to treat high-grade gliomas, including anaplastic astrocytoma and glioblastoma multiforme. Therapy-related secondary myelodysplastic syndrome and acute myeloid leukemia have been reported in patients following prolonged exposure to TMZ. However, TMZ-related acute lymphoblastic leukemia (ALL) is extremely rare. The present study describes the case of an 11-year-old boy with a 3-day history of generalized tonic-clonic seizures and a contrast-enhanced lesion in the left temporooccipital region with focal cystic degeneration, as detected by magnetic resonance imaging. The patient underwent craniotomy and gross-total resection andpathological analysis confirmed the diagnosis of giant cell glioblastoma. Postoperatively, the patient received TMZ-based concurrent chemoradiation during radiotherapy, and developed B-cell ALL 6 months following TMZ treatment. A thorough literature search identified only six published cases of TMZ-related ALL. The chemotherapeutic efficacy of TMZ has been identified, however, its leukemogenic potential should be emphasized among practitioners and patients. Further studies are required to determine the specific pathogenic mechanism of TMZ-related ALL. Close hematological monitoring of patients following TMZ treatment is vital and a high index of suspicion is necessary. IntroductionTemozolomide (TMZ) is a second-generation oral alkylating agent with the ability to penetrate the blood-brain barrier, and is widely used in the management of high-grade brain neoplasms, including anaplastic astrocytoma and glioblastoma multiforme, in addition to brain metastasis from solid tumors (1,2). TMZ is a prodrug and imidazotetrazine analog that exerts its action following spontaneous conversion to its active form, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (3). This active drug subsequently exerts its antitumor effect by methylating the purine bases of chromosomal DNA including O6-guanine, which results in the failure of DNA replication, cell cycle arrest and subsequent apoptosis (4,5). TMZ is generally considered effective and relatively safe (6-8); however, increased survival rates in certain patients have uncovered toxicities arising from the long-term use of alkylating agents, including TMZ (9). Treatment-related secondary myelodysplastic syndrome (t-MDS) and treatment-related acute myeloid leukemia (t-AML) have been recorded in patients following prolonged (5-10 years) exposure to alkylating agents (10-12).TMZ is a relatively new drug and glioblastoma is an aggressive neoplasm with poor prognosis, thus the types of secondary cancer arising due to TMZ treatment have not yet been fully characterized. A review of the existing literature demonstrated that only 7 cases of TMZ-related acute lymphoblastic leukemia (ALL) have been reported thus far (13-18). The current case describes an 11-year-old boy with glioblastoma multiforme, who develo...

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“…52 Thus, transplantation of ex vivo gene therapeutically modified HSCs would enable subsequent highdose chemotherapy with a reduced risk of myelosuppression and might be more beneficial than a standard autologous transplantation of unmodified HSCs after single high-dose chemotherapy. Gammaretro-or lentiviral transduction of HSCs is already an established technique that has been also applied in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

F2A sequence linking MGMTP140K and MDR1 in a bicistronic lentiviral vector enables efficient chemoprotection of haematopoietic stem cells

et al. 2012

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Chemoprotection of haematopoietic stem cells (HSCs) by gene therapeutic transfer of drug-resistance genes represents the encouraging approach to prevent myelosuppression, which is one of the most severe side effects in tumor therapy. Thus, we cloned and evaluated six different bicistronic lentiviral SIN vectors encoding two transgenes, MGMT P140K (an O 6 -benzylguanineresistant mutant of methylguanine-DNA methyltransferase) and MDR1 (multidrug resistance 1), using various linker sequences (IRESEMCV, IRESFMDV and 2A-element of FMDV (F2A)). Expression of both transgenes in HL-60 and in K562 cells was assayed by quantitative real-time PCR. Combination therapy with ACNU plus paclitaxel in HL-60 cells and with carmustin (BCNU) plus doxorubicin in K562 cells resulted in the most significant survival advantage of cells transduced with the lentiviral vector HR'SIN-MGMT P140K -F2A-MDR1 compared with untransduced cells. In human HSCs, overexpression of both transgenes by this vector also caused significantly increased survival and enrichment of transduced cells after treatment with BCNU plus doxorubicin or temozolomide plus paclitaxel. In summary, we could show significant chemoprotection by overexpression of MDR1 and MGMT P140K with a lentiviral vector using the F2A linker element in two different haematopoietic cell lines and in human primary HSCs with various combination regimens. Consequently, we are convinced that these in vitro investigations will help to improve combination chemotherapy regimens by reducing myelotoxic side effects and increasing the therapeutic efficiency.

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Secondary Ph+ acute lymphoblastic leukemia after temozolomide

Cited by 45 publications

References 6 publications

Mutagenic potential of temozolomide in bone marrow cells in vivo

Mutagenic potential of temozolomide in bone marrow cells in vivo

Acute lymphoblastic leukemia following temozolomide treatment in a patient with glioblastoma: A case report and review of the literature

F2A sequence linking MGMTP140K and MDR1 in a bicistronic lentiviral vector enables efficient chemoprotection of haematopoietic stem cells

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