It was 1995. The oncology nurses paged me to say that I should see this patient. She was a 33-year-old nurse who worked on the medical/pulmonary unit at our hospital. Admitted pancytopenic, she had just received a diagnosis of acute promyelocytic leukemia (APL). I knew her as being the Oncology Clinical Nurse Specialist; I frequently was consulted to see cancer patients off the oncology unit. Two weeks of standard induction chemotherapy at that time (Ara-C and Idarubicin) failed to elicit a response. ATRA (all-trans-retinoic acid) was requested from NIH/NCI for compassionate use. After 30 days of therapy, she experienced a complete response.
APL is a rare malignancy that historically was characterized as a rapidly fatal course of consumptive coagulopathy that almost uniformly ended in death.1, 2 Itís life-threatening nature is in part due to two emergent scenarios. Differentiation syndrome (previously referred to the retinoic acid syndrome) is a complication occurring during the initial phase of retinoic acid therapy administration. Dyspnea, interstitial pulmonary infiltrates, unexplained fever, weight gain, pleuro-pericardial effusions, hypotension, acute renal failure, and peripheral edema characterize this syndrome which is now managed with steroid prophylaxis. Pseudotumor cerebri is another complication most often seen in children with APL that presents as a severe headache with clinical signs of papilledema. Temporary discontinuation of ATRA is recommended to manage this complication along with analgesics, steroids, and diuretics.
The compound arsenic and its derivatives were first identified to have therapeutic potential over 2000 years ago in reports by both Chinese and Greek medicine. In the early 1990s, Chinese researchers reported complete APL clinical remissions due to arsenic-induced apoptosis in APL cells.3 The first United States intergroup trial utilizing a single agent to reverse the consequences of this fatal illness were reported in 1997.4 Since then, ATRA and its derivative ATO (arsenic trioxide) have revolutionized the treatment of APL transforming it from an almost automatic death sentence to a malignancy with a remarkable cure rate.5
While current treatment approaches have changed the course of this leukemiaís overall trajectory, questions remain. Central to these include the application of relevant interventions based on risk-stratification at diagnosis and the use of optimum maintenance therapies.2 Also, due to the novel nature of these drugs, potential long-term sequeale merit continued assessment as ATO is considered a carcinogen.
Zhu and colleagues in Shanghai evaluated 265 successfully treated patients with APL who received ATRA and ATO to determine levels of arsenic retention and chronic arseniasis.6 Their case review revealed plasma and urine levels of total arsenic comparable to healthy controls. However, mild liver dysfunction and hepatic steatosis was increased in APL survivors. Lastly, of note is the recent identification of favorable oral absorption of ATO that demonstrates comparable bioavailability to equivalent intravenous doses making this formulation a potential future treatment option.7, 8
The nature and management of APL offers testimony to the amazing benefits of ongoing bench and clinical research that is changing the landscape of many cancers. It demonstrates how advances in symptom recognition and management now offer patients the chance of cure when hope in the past seemed only a remote possibility. APL and its ramifications are also an exemplar of the need for astute, assertive, and conscientious nursing care required of these patients who can become so critically ill shortly after diagnosis.
The case I shared at the beginning of this blog occurred 21 years ago. The patient now has worked for 18 years as an oncology nurse in a busy infusion center. I still periodically see her. To me, she is an enduring reminder of the amazing potential of contemporary cancer care.
Cicconi L, Lo-Coco F. Current management of newly diagnosed acute promyelocytic leukemia. Ann Oncol. 2016 Aug;27(8):1474-81.
Coombs CC, Tavakkoli M, Tallman MS. Acute promyelocytic leukemia: Where did we start, where are we now, and the future. Blood Cancer J. 2015 Apr 17;5:e304.
Falchi L, Verstovsek S, Ravandi-Kashani F, Kantarjian HM. The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy. Cancer. 2016 Apr 15;122(8):1160-8.
Tallman MS, Andersen JW, Schiffer CA, et al. All-trans-retenoic-acid in acute promyelocytic leukemia. N Engl J Med. 1997 Oct 9;337(15):1021-8.
Zhu H, Hu J, Chen L, et al. The 12-year follow-up of survival, chronic adverse effects and retention of arsenic in patients with acute promyelocytic leukemia. Blood. 2016 Jul 11. pii: blood-2016-02-699439.
Au WY, Kumana CR, Lee HK, et al. Oral arsenic trioxide-based maintenance regimens for first complete remission of acute promyelocytic leukemia: A 10-year follow-up study. Blood. 2011 Dec 15;118(25):6535-43.
Zhu HH, Wu DP, Jin J, et al. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: A multicenter randomized controlled trial. J Clin Oncol. 2013 Nov 20;31(33):4215-21.
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