Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report
Abstract Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neop...
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-019-0880-1 |
| _version_ | 1818721009648271360 |
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| author | Mingming Li Wei Chen Xiaomeng Sun Zhipeng Wang Xun Zou Hua Wei Zhan Wang Wansheng Chen |
| author_facet | Mingming Li Wei Chen Xiaomeng Sun Zhipeng Wang Xun Zou Hua Wei Zhan Wang Wansheng Chen |
| author_sort | Mingming Li |
| collection | DOAJ |
| description | Abstract Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC. Case presentation In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months. Conclusions This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC. |
| first_indexed | 2024-12-17T20:31:55Z |
| format | Article |
| id | doaj.art-3a31bfff013a428e9ced075e4a776414 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-17T20:31:55Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-3a31bfff013a428e9ced075e4a7764142022-12-21T21:33:34ZengBMCBMC Medical Genetics1471-23502019-09-012011710.1186/s12881-019-0880-1Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case reportMingming Li0Wei Chen1Xiaomeng Sun2Zhipeng Wang3Xun Zou4Hua Wei5Zhan Wang6Wansheng Chen7Department of Pharmacy, Changzheng Hospital, Secondary Military Medical UniversityDepartment of Pharmacy, Changzheng Hospital, Secondary Military Medical UniversityInstitutes of Biomedical Sciences, Fudan UniversityDepartment of Pharmacy, Changzheng Hospital, Secondary Military Medical UniversityDepartment of Pharmacy, Changzheng Hospital, Secondary Military Medical UniversityDepartment of Pharmacy, Changzheng Hospital, Secondary Military Medical UniversityDepartment of Oncology, Changzheng Hospital, Secondary Military Medical UniversityDepartment of Pharmacy, Changzheng Hospital, Secondary Military Medical UniversityAbstract Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC. Case presentation In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months. Conclusions This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC.http://link.springer.com/article/10.1186/s12881-019-0880-1X-linked agammaglobulinemiaHypocalcemiaWhole exome sequencingTherapeutic drug monitoringAnd irinotecan |
| spellingShingle | Mingming Li Wei Chen Xiaomeng Sun Zhipeng Wang Xun Zou Hua Wei Zhan Wang Wansheng Chen Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report BMC Medical Genetics X-linked agammaglobulinemia Hypocalcemia Whole exome sequencing Therapeutic drug monitoring And irinotecan |
| title | Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report |
| title_full | Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report |
| title_fullStr | Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report |
| title_full_unstemmed | Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report |
| title_short | Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report |
| title_sort | metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with x linked agammaglobulinemia a case report |
| topic | X-linked agammaglobulinemia Hypocalcemia Whole exome sequencing Therapeutic drug monitoring And irinotecan |
| url | http://link.springer.com/article/10.1186/s12881-019-0880-1 |
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