The patient, a 32-year-old female with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia diagnosed in 2019, presented with a ten-day history of increasing dyspnea, tachycardia, and chest pain. She is originally from Guatemala; however, she had not returned to Guatemala for approximately fifteen years. Her medical history is also notable for drug-induced hyperglycemia and obesity.
In April 2019, she was admitted for a one-month history of fatigue, lethargy, and diffuse pain in her spine and upper and lower extremities. At the time, she had noticed new bruising in her skin without any significant trauma. Blood tests showed a white blood cell count of 55,000 x 109/L with increased blasts. Her peripheral blood smear showed normochromic, normocytic anemia, thrombocytopenia, and 88% blasts. CT imaging studies demonstrated a right breast mass and spinal lesions. Bone marrow aspiration and biopsy showed acute B-lymphoblastic leukemia (B-ALL) with t(9;22)(q34.1;q11.2) BCR-ABL1. Analysis by FISH was abnormal and indicated approximately 90% of nuclei with BCR/ABL1 fusion and a partial ETV6 deletion as well as a partial CDKN2A deletion in 61.5% of nuclei. She underwent induction chemotherapy with AYA protocol (AALL 0232), which consisted of a tyrosine kinase inhibitor plus a hyper-CVAD regimen and bone marrow transplant. Additionally, she received central nervous system (CNS) prophylaxis with intrathecal methotrexate and ARA-C per protocol. On day 28, after bone marrow transplant, she was negative for minimal residual disease and was discharged on dasatinib.
In August 2019, she was started on maintenance with a POMP regimen (6-mercaptopurine, vincristine, methotrexate, prednisone), and in January 2020, she relapsed with blasts in the cerebrospinal fluid (CSF). The POMP regimen was switched to high-dose methotrexate. Due to persistent CNS disease, she received intrathecal methotrexate, cytarabine, and hydrocortisone every two weeks for five cycles. The treatment was briefly interrupted due to COVID-19 infection and resumed in July of 2020. In November 2020, the patient was admitted with complete vision loss in the right eye. Magnetic resonance imaging (MRI) showed concern for leukemic infiltration of the right optic nerve and a new pineal mass. The patient underwent whole-brain radiotherapy in 10 fractions. In January of 2021, she was re-admitted with leukocytosis and circulating blasts. At this time, a CT scan showed hepatosplenomegaly and numerous lytic lesion in the axial skeleton. She received one cycle of etoposide, ifosfamide, and mitoxantrone. In February 2021, the patient started systemic chemotherapy with hyper-CVAD, and in May 2021, cycle 3 part A was interrupted because of interval development of acute appendicitis requiring emergent surgery. The surgical specimen only showed pathologic alterations associated with appendicitis. In June of 2021, the patient completed cycle 3, part B.
A month later, at the time of admission for her scheduled hyper-CVAD cycle 4 part B treatment, she developed shortness of breath, central and left chest pain that worsened with inspiration, non-productive cough, back pain, and epigastric pain. Additionally, she developed acute hypoxic respiratory failure, so the chemotherapy was held. On admission, she was afebrile and had an elevated ESR of 46.0 mm/hr. Initial absolute eosinophil count was within normal range, however, twelve days later, it was increased at 7.67 x 10(9)/L and twenty-three days later decreased to 2.13 x 10(9)/L. (Fig. 1). Concurrently, she developed a diffuse pruritic maculopapular rash bilaterally on the scapular region, right thigh, and knee. The primary differential diagnosis was herpes zoster infection related to dermatitis. However, dermatology was consulted and attributed the cause of her rash to her prescribed Percocet.
Blood cultures were obtained; one out of two were positive for coagulase-negative staphylococci, likely a contaminant and fungal cultures were negative. Additionally, despite of being tested positive for Mycobacterium tuberculosis by QuantiFERON-TB Gold three months before this admission and treated with Isoniazid for latent tuberculosis infection, current respiratory cultures for Mycobacteria were negative.
A new chest CT scan demonstrated bilateral pulmonary focal ground-glass opacities and interlobular septal thickening, consistent with pulmonary edema. Small pericardial effusion and mild bilateral hilar and mediastinal lymphadenopathy were also identified. Overall findings, in conjunction with an ejection fraction of 65% on echocardiogram, non-cardiogenic pulmonary edema, and pericardial effusion were favored (Fig. 2). Due to the treatment with multiple cardiotoxic chemotherapeutic agents since 2019, possible pneumonitis secondary to chemotoxicity was included as a probable differential diagnosis. The patient's chest CT scan findings lacked diffuse ground-glass opacities (GGOs), common to many infectious processes and incredibly opportunistic infections. Cyclophosphamide, cytarabine, doxorubicin, and Methotrexate are capable of causing interstitial non-cardiogenic pulmonary edema and pericardial effusion. The patient received intravenous methylprednisolone, and a bronchoscopy with brochoalveolar lavage (BAL) was performed. Forty milliliters of pink fluid with mucoid material was placed in ThinPrep  CytoLyt solution (methanol-based buffered preservative solution) and sent to cytology for further processing and analysis. A ThinPrep slide and two cytospins, one stained with Giemsa stain and the second one stained with Grocott's Methenamine Silver stains (GMS), were performed. Numerous filariform larvae with short buccal cavity and prominent genital primordium were identified, consistent with Strongyloides. These morphologic findings were consistent with Strongyloides, thus leading to the diagnosis of Strongyloides hyperinfection (Fig. 3, Fig. 4). Stool analysis was negative for ova and parasites (O&P). She was started on Ivermectin (200 mcg/kg/day) for two weeks. Thirteen days later, pathology confirmed the newly submitted specimen after treatment was negative for parasites, despite persistent eosinophilia (absolute eosinophil count of 2.64 x10(9)/L). The patient's follow-up course was further complicated with right-sided blindness, latent tuberculosis infection, and chronic pain at direct admission for chemotherapy. Her stool O&P was negative for Strongyloides larvae. Given the patient's multiple systemic comorbidities secondary to her relapsed ALL, the palliative care team was consulted to collaborate in future care and management of this patient.