In October 2016, a 40-year-old woman was admitted to another hospital for a diagnosis of BC. One month prior to admission, a routinary mammography had shown the presence of a mass of 15 mm in diameter confirmed by a subsequent MRI scan. She was treated with right quadrantectomy and axillary dissection, and the histopathology provided a diagnosis of grade III invasive poorly differentiated ductal carcinoma. Immunohistochemistry was positive for estrogen and progesterone receptors (75%), with a high Ki67 proliferation index (30%) and mild expression of HER-2 (+1). However, fluorescent in situ hybridization for the HER2 gene was negative (staging pT1N2M0). In November, she started adjuvant chemotherapy regimen with doxorubicin 60 mg/m2/day and cyclophosphamide 600 mg/m2/day for 4 cycles, followed by maintenance with paclitaxel 80 mg/m2 since April 2017 and endocrine therapy with tamoxifen. Peripheral blood cell count at the start of chemotherapy showed leukopenia (white blood cells count 1.0 x 109/L), not further investigated, with mild anemia (hemoglobin 11.6 g/dl) and normal platelets count (168 x 109/L). In June 2017, during breast adjuvant radiotherapy, the patient was persistently pancytopenic (hemoglobin 9.6 g/dl, white blood cells 0.9 x 109/L, and platelets 101 x 109/L). Bone marrow was cellular (+3) and showed 82% of CD34/CD117/CD13+ and CD33/CD7/CD11b/CD14/cMPO blasts of small-medium size, round nucleus, and basophilic cytoplasm with rare granules, consistent with a diagnosis of AML. Cytogenetic analysis showed a normal karyotype (46, XX), and the gene mutation status was wild type for FLT3/ITD and TKD, AML1/ETO, Cbf/MYH11, NPM1, PML-RARalpha, BCR-ABL1, and MLL. The patient was treated with ICE induction chemotherapy, consisting of a combination of idarubicin 10 mg/m2 days 1, 3, and 5, cytarabine 100 mg/m2 days 1-7, and etoposide 100 mg/m2 days 1-5, but proved refractory. In September 2017, the patient was referred to our centre and underwent a salvage chemotherapy with the G-CLAC schedule: clofarabine 30 mg/m2 days 1-5, cytarabine 2000 mg/m2 days 1-5, and granulocyte colony stimulating factor (G-CSF) until hemopoietic recovery. On day +13 from chemotherapy, the patient was pancytopenic (hemoglobin 8.5 g/dl, white blood cells 0.750 x 109/L, neutrophils 0.2 x 109/L, and platelets 20 x 109/L) and presented a septic shock, associated with acute abdominal pain with positive Murphy sign and positive blood cultures for Escherichia coli, Staphylococcus haemolyticus, and Candida glabrata. She received antibiotic and antifungal treatment (meropenem, tigecycline, and caspofungin) and supportive care with fluids and inotropic agents. An abdominal ultrasound and an MRI allowed to make a diagnosis of acute cholecistytis and in October 2017 (on day +30 from chemotherapy), after a full hematologic recovery, she underwent a laparoscopic cholecystectomy. The microbiologic examination of pericholecistic liquid revealed a multidrug-resistant Pseudomonas aeruginosa. In the same period, she became a KPC-Klebsiella pneumoniae rectal carrier. On day +35, the bone marrow aspiration showed a complete remission (CR). For this reason, in November 2017, on day +56 from chemotherapy, she underwent an allogeneic hematopoietic stem cell transplantation (HSCT) from the haploidentical brother after a preparative regimen with TBF (thiotepa 5 mg/kg days -7, -6; fludarabine 50 mg/m2 days -5, -4, -3; busulfan 3.2 mg/kg days -5, -4, -3). No major toxicity was observed during the aplastic phase, and the engraftment was obtained on day +17 for PMN and on day +25 for platelets. On day +20, the bone marrow aspirate confirmed a CR with complete donor chimerism, and on day +30, the patient was discharged.
Two months after discharge, she was readmitted to the hospital due to an acute left chest pain, fever, and neutropenia (hemoglobin 8.9 g/dl, white blood cells 0.62 x 109/L, neutrophils 0.34 x 109/L, and platelets 21 x 109/L); chest computed tomographic scan showed a basal bilateral pneumonia associated with diffuse pulmonary nodules and bronchial obliteration. A microbiological examination of bronchoalveolar lavage proved the presence of a Nocardia spp. Despite targeted antibiotic therapy with high-dose sulfametoxazole-trimethoprim in association with broad-spectrum and specific antibiotics in different timing (amikacin, ceftadizime-avibactam, levoxacin, ceftolozane-tazobactam, tigecycline, imipenem, and linezolid), pulmonary nocardial lesions persisted (and progressed toward) with the formation of a pulmonary organized abscess (Figure 1). Due to the persistence of fever and worsening of clinical conditions, the patient was submitted to a lower pulmonary lobectomy by left lateral thoracotomy; histological examination confirmed the presence of a Nocardia spp. She had a good postoperative course with disappearance of fever and complete resolution of the pneumonia.
Currently, the patient is alive in continuous CR for AML and BC, with a follow-up from diagnosis of 29 months and 37 months, respectively. She is in good general conditions with an excellent quality of life.