Prolonged and severe thrombocytopenia with pancytopenia induced by radiation-combined temozolomide therapy in a patient with newly diagnosed glioblastoma—analysis of O 6-methylguanine-DNA methyltransferase status

Nagane, Motoo; Nozue, Kyoko; Shimizu, Saki; Waha, Andreas; Miyazaki, Hiroshi; Kurita, Hiroki; Hòmori, Masashi; Fujioka, Yasunori; Shiokawa, Yoshiaki

doi:10.1007/s11060-008-9754-7

Cited by 19 publications

(17 citation statements)

References 16 publications

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“…However, the role of methylated MGMT gene promoter status and excessive hematological toxicities could not be consistently demonstrated. [14,21,72,73]. Two small studies identified an association between genotype polymorphism and higher risk for TMZ-related profound myelosuppression [21,72].…”

Section: Discussionmentioning

confidence: 99%

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Temozolomide-related idiosyncratic and other uncommon toxicities

Dixit

Baker²,

Walmsley³

et al. 2012

Anti-Cancer Drugs

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Temozolomide (TMZ)-related idiosyncratic and other uncommon toxicities have been reported. To better characterize these toxicities and to identify any associated risk factors, we performed a systematic review. We searched the PubMed database, limited to the English language, published between 1999 and December 2011. We selected only those articles in which TMZ was temporally related and was the sole or main contributing chemotherapeutic drug to idiosyncratic drug reactions (IDRs) and other uncommon toxicities. Hematological IDRs are biopsy-proven aplastic anemia or grade V toxicity or grade IV toxicity with slow and incomplete hematological recovery. Seventy-three cases were identified, including 21 hematological IDRs, 31 nonhematological IDRs and uncommon infections, and 21 second primary cancers. With a caveat of publication and reporting bias, the following observations could be made. The hematological IDRs predominantly occurred in female patients (exact binomial two-tailed, P=0.0041) and most patients were receiving TMZ concomitantly with radiotherapy for glioma. The median duration of exposure to TMZ was 30 days and the median cumulative TMZ exposure was 2250 mg/m (range, 500-6900 mg/m). The sex predilection was not evident in nonhematological IDRs and other uncommon toxicities. TMZ-induced pneumonitis and cholestatic hepatitis are emerging as a nonhematological hypersensitive reaction and IDR, respectively. For TMZ-related myelodysplasia or leukemia, the cumulative dose of TMZ ranged from 1400 to 30 000 mg/m. The cumulative dose of TMZ was lower and latency was shorter with a previous exposure to other leukemogenic drugs, suggesting that TMZ may have augmented the leukemogenic potential of other drugs. Early appearance of profound myelosuppression during the course of TMZ and concurrent radiotherapy could be a hematological IDR, which warrants prompt investigations to exclude aplastic anemia. Myelodysplasia or leukemia developed after a median TMZ exposure of 15 g/m.

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Section: Discussionmentioning

confidence: 99%

“…We analyzed 21 cases of TMZ-related hematological IDRs, including one case of grade V myelosuppression, which we encountered at our center [5,6,[9][10][11][12][13][14][15][16][17][18][19][20][21] (Table 1). Information about sex was available for 16 cases; there were 12 female and four male patients.…”

Section: Hematological Idiosyncratic Drug Reactionsmentioning

confidence: 99%

Temozolomide-related idiosyncratic and other uncommon toxicities

Dixit

Baker²,

Walmsley³

et al. 2012

Anti-Cancer Drugs

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“…Nagane et al [3], Jalali et al [2] and Singhal et al [4] report a total of 4 cases with long-lasting myelosuppression after temozolomide (one patient has died of sepsis).…”

Section: Discussionmentioning

confidence: 99%

Toxicity after radiochemotherapy for glioblastoma using temozolomide - a retrospective evaluation

et al. 2011

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PurposeRetrospective evaluation of toxicity and results after radiochemotherapy for glioblastoma.Methods46 patients with histopathologically proven glioblastoma received simultaneous radiochemotherapy (RCT). The mean age at the beginning of therapy was 59 years, the mean Karnofsky performance index 80%. 44 patients had been operated on before radiotherapy, two had not. A total dose of 60 Gy was applied in daily single fractions of 2.0 Gy within six weeks, 75 mg/m2/day Temozolomide were given orally during the whole radiotherapy period.ResultsA local progression could be diagnosed in 34/46 patients (70%). The median survival time amounted to 13.6 months resulting in one-year and two-year survival probabilities of 48% and 8%, respectively.Radiotherapy could be applied completely in 89% of the patients. Chemotherapy could be completed according to schedule only in 56.5%, the main reason being blood toxicity (50% of the interruptions). Most of those patients suffered from leucopenia and/or thrombopenia grade III and IV CTC (Common toxicity criteria). Further reasons were an unfavourable general health status or a rise of liver enzymes.The mean duration of thrombopenia and leucopenia amounted to 64 and 20 days. In two patients, blood cell counts remained abnormal until death. In two patients we noticed a rise of liver enzymes. In one of these in the healing phase of hepatitis a rise of ASAT and ALAT CTC grade IV was diagnosed. These values normalized after termination of temozolomide medication. One patient died of pneumonia during therapy.ConclusionOur survival data were well within the range taken from the literature. However, we noticed a considerable frequency and intensity of side effects to bone marrow and liver. These lead to the recommendations that regular examinations of blood cell count and liver enzymes should be performed during therapy and temozolomide should not be applied or application should be terminated according to the criteria given by the manufacturer.

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“…The case was investigated for a possible relationship between methylguanine-DNA methyltransferase status and pancytopenia. However, Nagane et al [11] found out that there is not a remarkable relationship between methylguanine-DNA methyltransferase status and pancytopenia.…”

Section: Discussionmentioning

confidence: 99%

Another Cause of Pancytopenia in a Patient Receiving Temozolomide

Pehlıvan¹,

Sevinç²,

Türkbeyler³

et al. 2011

Med Princ Pract

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Objective: To report pancytopenia caused by temozolomide, a second-generation alkylating agent. Clinical Presentation and Intervention: A 22-year-old patient presenting with seizures and confusion was seen in the emergency room. Cranial magnetic resonance imaging revealed a mass. After surgery, the patient was diagnosed with glioblastoma multiforme and was given temozolomide at 150 mg/m² on days 1 through 5 every 4 weeks. During the last cycle of temozolomide, grade 3 thrombocytopenia persisted. Possible causes of pancytopenia including vitamin B₁₂ deficiency were investigated. Conclusion: This case report shows that vitamin B₁₂ deficiency can be a potential cause of pancytopenia and it should be kept in mind for patients receiving chemotherapy.

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Prolonged and severe thrombocytopenia with pancytopenia induced by radiation-combined temozolomide therapy in a patient with newly diagnosed glioblastoma—analysis of O 6-methylguanine-DNA methyltransferase status

Cited by 19 publications

References 16 publications

Temozolomide-related idiosyncratic and other uncommon toxicities

Temozolomide-related idiosyncratic and other uncommon toxicities

Toxicity after radiochemotherapy for glioblastoma using temozolomide - a retrospective evaluation

Another Cause of Pancytopenia in a Patient Receiving Temozolomide

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