Cancer Case Study

Mark's Clinical Presentation and Diagnosis

Mark was a 20-year-old man who had been in his usual state of good health until approximately 10 days prior to presentation. At that time, he started to feel fatigued. His parents noted that he was asleep for most of the day. Soon thereafter, Mark noticed that his bedsheets were wet from sweating in the middle of the night. On the day prior to presentation, he had gone to the dentist for a regularly scheduled visit to have his teeth cleaned. This visit was uneventful, but soon thereafter Mark’s gums were oozing blood. He went to bed, and awoke the next morning with significant bleeding from his mouth. He then presented to the hospital for evaluation.

On presentation to the emergency room, Mark was found to be weak, with low-grade fever, and with bleeding from his gums. His blood counts were markedly abnormal, with a WBC of 34,000/μl (normal is 4000–11,000/μl), hemoglobin of 8.5 g/dl (normal, 12–16 g/dl), and a platelet count of 12,000/μl (normal, 150,000–400,000/μl). The Hematology-oncology team was consulted and noted a circulating population of large, abnormal-appearing cells with azurophilic granules and bilobed nuclei on the peripheral blood smear (See Figure 1). Mark showed a elevated prothrombin time (PT) and a very low fibrinogen level.  These laboratory abnormalities suggested disseminated intravacular coagulation (DIC) so blood product support with plasma, cryoprecipitate, and platelets was administered.  A bone marrow biolsy was performed and sent for hematopathologic and cytogenetic evaluation.

Mark was admitted to the hospital, closely monitored for DIC, and his fibrinogen and coagulation levels stabilized, and oozing of blood from his mouth ceased but he was placed immediately on all-trans retinoic acid (ATRA).  After 48 hours, molecular cytogenetic analysis results came back with a translocation of chromosome 15 and 17.  With this result Mark ATRA was continued and chemotherapy started on Day 4.  It was noted that over the next week his WBC was steadily climbing to 40,000/µL and then to 55,000/µL on ATRA and developed worsening dyspnea requiring oxygen, which is consistent with differentiation syndrome that complicates initial treatment in one-quester of patients with this cancer.  

Mark was treated with intravenous dexamethasone (steroid), which led to an improvement in his hypoxia and respiratory symptoms.  He went on to tolerate induction chemotherapy with the drugs daunorubicin and cytarabine without other complications.

 
30-days later, a bone marrow biopsy was performed that revealed a morphologic remission but PCR test was done and still detected PML-RARA.  Mark went on to receive four cycles of consolidation chemotherapy, after which a repeat bone marrow biopsy no longer revealed a product in the PML-RARA PCR test, suggesting molecular remission.  Mark was placed on prolonged maintenance therapy with ATRA that was well tolerated apart from intermittent mild headaches.

Mark remains in remission and free of cancer three years later.  

1. What is the specific type of cancer that Mark was diagnosed with by the Oncology team before he was treated with chemotherapy?

2. What is the underlying chromosomal abnormality that occurs with the translocation above and explain how it causes this type of cancer?

3. Mark was treated with ATRA right away as part of the therapy why was this done? Why might this strategy not work for other types of cancer?

4. What are the most common complications with ATRA treatment?

5. What are some other acceptable therapeutic paradigms for the induction chemotherapy treatment of Mark (other than the two drugs that were used).