Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 5, Num. 4, 2009, pp. 302-304

Journal of Cancer Research and Therapeutics, Vol. 5, No. 4, October-December, 2009, pp. 302-304

Case Report

Acute myelogenous leukemia following treatment of invasive cervix carcinoma: A case report and a review of the literature

Samanta DiptiR, Senapati SurendraN, Sharma PraveenK, Mohanty Asit, Samantaray Sagarika

Division of Radiation Oncology, Medical Oncology, and Oncopathology, A. H. Regional Cancer Centre, Cuttack, Orissa

Correspondence Address:A. H. Regional Cancer Centre, Mangalabag, Cuttack -753 007, Orissa
diptiranisamanta@rediffmail.com

Code Number: cr09072

PMID: 20160368

DOI: 10.4103/0973-1482.59918

Abstract

Keywords: Acute myelogenous leukemia, carcinoma cervix, second malignancy

Introduction

With the introduction of the multidisciplinary approach in the treatment of cancer, the disease-free survival and overall survival have considerably increased. Carcinoma cervix is the commonest female genital malignancy in developing countries. Majority of the patients present with the advanced disease. Cisplatinum-based concurrent chemoradiation is now the cornerstone of concurrent chemoradiation in the treatment of carcinoma cervix that has improved the survival. Due to the prolonged survival, treatment-related second malignancy is also increasingly being recognized. Klinerman et al. first reported the treatment-related second malignancy in a patient of carcinoma cervix. ^[1] Acute myelogenous leukemia (AML) is one of the uncommon, treatment-related second malignancies after a successful treatment of a prior malignancy with radiation.

Here, we report a case of AML, which developed 63 months after the completion of the treatment of carcinoma cervix IB with concurrent cisplatinum and radiation in a female. This case needs reporting and documentation because of its rarity.

Case Report

A 54-year-old female clinically presented with the history of vaginal whitish discharge as well as postcoital bleeding of 4 months′ duration. Clinical evaluation revealed an infiltrative type of lesion, involving both the lips of the cervix without any vagina or parametrium involvement. Histopathology of the cervical lesion was moderately differentiated squamous cell carcinoma. Routine hematological parameters were within normal limits. An X-ray of the chest, and ultrasonography of the abdomen and pelvis excluded the possibilities of any metastatic disease. Patient was diagnosed as carcinoma cervix stage IB. She had undergone Wertheim′s hysterectomy in November 2001. Histopathology of the primary lesion was moderately differentiated squamous cell carcinoma. There was endocervical extension, and right external iliac and left internal iliac lymph nodes were positive for carcinoma. Patient was subsequently treated with external beam radiation to the pelvis by opposing pair portals by cobalt 60 to a total dose of 50 Gy/25 fractions in 5 weeks followed by brachytherapy to vaginal vault of 7 Gy each in two sittings. She also received concurrent cisplatinum at a dose of 40 mg/m ² body surface in total five cycles. She was on regular follow-up and had locoregional control of the disease.

In April 2007, after 63 months of the treatment, she presented with fever and easy fatigability of 2 months′ duration. Physical examination did not reveal any locoregional or distant disease due to carcinoma cervix, except pallor. Her routine blood picture was Hb 9 gm%, total WBC count 8000/cumm, total platelet-2 lacs/cumm, differential count--neutrophils-14%, eosinophils- 03%, lymphocytes- 8%, premature blasts -75%. The peripheral blood picture revealed blast cells which showed Auer rods and were myeloperoxidase positive, suggestive of AML (M2). The bone marrow showed that more than 70% of nucleated cells were blast cells which were myeloperoxidase positive with the presence of Auer rods in most of these cells [Figure - 1]. Immunohistochemistry of peripheral blood leucocytes revealed that 35.13% of leucocytes were positive for CD13 and 81.65% positive for CD33, suggestive of AML-M2 [Figure - 2].

The patient was diagnosed as AML (M2). She was treated with a 3+7 regimen, i.e., combination of Daunomycin 60 mg/m ² , IV bolus on Days 1-3 and Ara-C 100 mg/m ² as continuous infusion on Days 1-7. A bone marrow examination was repeated on Day 10 of chemotherapy and the bone marrow did not undergo remission. She was subjected to high-dose Ara-C 1.5 g/m ² as 1-h infusion at 12-h intervals from Day 1 to 5. Her bone marrow did not undergo remission and she died due to the disease.

Discussion

Second malignant neoplasms are distinct entities, having definitive pictures of malignancy, being histologically different from the primary neoplasm, without any metastatic deposit from the primary. ^[2] The reported patient was a case of AML (M2) which developed 63 months after the treatment of carcinoma cervix IB.

Therapy-induced second malignant neoplasms occur due to either ionizing radiation or chemotherapy, or both. Radiation induces nonlethal DNA damage to the bone marrow which subsequently undergoes malignant transformation resulting in leukemia. ^[3] Chaturvedi et al., on analysis of 104,760 cervical cancer survivors, observed a significant elevated relative risk (RR = 1.3; 95% CI, 1.28-1.33) of second malignancies following radiation to the pelvis. ^[4] Various chemotherapatic drugs such as alkylating agents, topoisomerases, and platinum compounds induce the leukemia. Platinum compounds are mutagenic in vitro and laboratory animals producing intrastrand and interstrand DNA crosslinks. ^[5] The persistence of DNA adduct in the bone marrow long after the completion of treatment also heightens the possibilities of late complications. ^[6] Howard et al. observed secondary leukemia in 89 patients out of 42,722 testis cancer survivors from -a cancer registry based on 14 populations. In this study, a statistically significant elevated risk was observed for AML and acute lymphoblastic leukemia. In a multivariate analysis, the AML risk was higher among patients whose initial management was platinum-based chemotherapy rather than radiation alone.^{" [7]} The relative risk of the development of platinum-induced leukemia depends on the cumulative dose of platinum, length of the treatment, and age of the patient. Travis et al. observed that the relative risk of leukemia in survivors of carcinoma ovary treated with platinum-based chemotherapy was 1.9, 2.1, 4.1, and 7.6, when the cumulative dose of platinum was 500 mg, 500-749 mg, 750-999 mg, and 1000 mg or more, respectively. ^[8] Radiation given concurrent with platinum also increases the cacinogenic potential of the platinum compound. ^[9] This patient was treated with cisplatinum with a cumulative dose of 300 mg, and concurrent radiation seems to be the cause of development of AML.

Ballen et al. suggested that the mean time of onset of secondary leukemia was 4.5 years and of solid malignancy 12 years following the treatment of Hodgkin′s disease. Adult survivors of Hodgkin′s disease after more than 10 years of treatment did not have increased risk of leukemia. However, the risk keeps on increasing with time in solid malignancy. ^[10] The present case developed AML (M2) 63 months after the treatment for carcinoma cervix.

Patients of therapy-related secondary AML on flowcytometry express CD markers, i.e., CD13, CD15, CD33, and CD117. The cluster differentiation classification has a high sensitivity and specificity for diagnosis and types of AML. In this patient, 35.13% of peripheral blood leucocytes were positive for CD 13 and 81.65% positive for CD 33, suggesting AML-M2.

Therapy induced AML patients are refractory to conventional treatment of acute myeloid leukemia and their median survival ranges from 2-8 months. ^[11] This patient was treated with standard 3+7 regimen of Daunomycin and Ara-C .She did not respond to treatment and died due to disease.

Conclusion

Patients of carcinoma cervix treated with chemoradiation, even though survival has improved, are more prone to the development of therapy-related second malignancies. Clinicians should be aware of such complications whose prognosis is really poor.

References

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