Administration of all-trans retinoic acid through enteral tubes in acute promyelocytic leukemia: the handling of cytotoxic agents and clinical benefits

Acute promyelocytic leukemia (APL) is one of the most incident hematologic neoplasms in the acute care setting.1 Treatment of APL consists of oral all-trans retinoic acid (ATRA), which has been extensively studied since 1990.1 The pharmacological target of ATRA is the Retinoic Acid ReceptorAlfa (RAR) in malignant promyelocytes where it promotes their differentiation into mature myeloid lineages. Nowadays, 90% of patients achieve complete remission status in one to three months. Depending on risk classification, ATRA can be used as oral monotherapy, or combined with arsenic trioxide or anthracyclines.2 Despite the high rates of disease remission, APL is a medical emergency, as it causes a life-threatening coagulation disorder and respiratory insufficiency. The latter may be a result of differentiation syndrome (DS), which comprises 30% of all causes of deaths in the APL population.3 When patients are diagnosed with DS, they are often intubated to restore ventilation parameters. They also require the placement of an enteral tube to receive nutrients and medications. So, how can we keep administering ATRA to these patients? In other words, the risk of occupational exposure to ATRA does not allow the nursing staff to manipulate such drugs by puncturing the capsule. Moreover, extracting the oily content from the hard-coated jelly capsules may lead to significant ATRA losses.4 In our institution, we have been admitting from two to eight patients per year with APL/DS to the emergency room and intensive care units. Because of the aforementioned ATRA handling problems, we have seen dose administration delays, unaware nursing technicians trying to manipulate ATRA (some of them in the fertile age) and pharmacy staff recurrently asking how to prepare this drug without losses and unnecessary occupational exposure. Unfortunately, there is not enough published information to support any kind of initiative, possibly due to the quick clinical evolution of APL and relatively low incidence in comparison to other neoplasms.5 In one of the most recent cases that we accompanied, we standardized a protocol to administer ATRA to intubated patients. A 22-year-old woman was admitted to the emergency room with dyspnea, dry cough and 85% oxygen saturation. She was diagnosed with high-risk PML and induction chemotherapy was promptly initiated: 50 mg/m2 daunorubicin plus ATRA 45 mg/m2/day. Two days later, her ventilatory parameters worsened due to DS, so she was intubated and an enteral tube was inserted. As DS is an ATRA-related life-threatening condition, the retinoid was suspended for two days until her respiratory parameters improved. When ATRA was reintroduced, the problem of administering it by enteral tube arose, as her oral access was no longer available. After conducting a literature review, we suggest the following procedure (Figure 1):