Late Ovarian and Intestinal Extramedullary Relapse of Acute Myeloid Leukemia with Inv 16 after Allogeneic Hematopoietic Stem Cell Transplantation

Case Report

Ann Hematol Oncol. 2018; 5(3): 1199.

Late Ovarian and Intestinal Extramedullary Relapse of Acute Myeloid Leukemia with Inv 16 after Allogeneic Hematopoietic Stem Cell Transplantation

Mensah-Glanowska P1*, Glanowski D2, Sporek- Kunicka A1, Kviatkouskaya K1, Szostek M1, Piatkowska-Jakubas B1 and Skotnicki AB1

1Department of Haematology, University Hospital in Krakow, Jagiellonian University Collegium Medicum, Poland

2Department of Obstetrics and Gynecology with Oncology, Gabriel Narutowicz Specialized Municipal Hospital in Krakow, Poland

*Corresponding author: Mensah-Glanowska P, Department of Hematology, University Hospital in Krakow, Jagiellonian University Collegium Medicum, 17 Kopernika St, 31-501, Krakow, Poland

Received: March 29, 2018; Accepted: April 17, 2018; Published: May 09, 2018


Treatment of acute myeloid leukemia (AML) extramedullary relapse (EMR) after allogenic hematopoietic stem cell transplantation (alloHSCT) is challenging. EMR pathogenesis of this entity is not clearly elucidated. Variety of factors affect clinical approaches in diagnostics, treatment and prognosis. Furthermore, there is no current consensus for post-transplant AML EMR treatment. We present here the case of young AML female patient with rare EMR presentation: ovary and large intestine infiltration. The treatment combined different strategies – conservative like surgery and chemotherapy, but also effective new approaches of targeted therapy - hypomethylating agent with tyrosine kinase inhibitor.

Keywords: Extramedullary relapse; AML; AlloHSCT; PET/CT


AML: Acute Myeloid Leukemia; BAL: Bronchoalveolar Lavage ; CBF: Core Binding Factor; FAM: Fluticasone/Azitromycine/ Montelukast; FDG: Fluorodeoxyglucose; HRCT: High Resolution Computed Tomography; MIP: Maximum Intensity Projection; MRD: Minimal Residual Disease; PET/CT: Positron Emission Tomography/Computed Tomography; SIRS: Systemic Inflammatory Response Syndrome; SUVmax: Maximal Standardized Uptake Value; TK: Tyrosine Kinase

Case Presentation

23-year-old female patient was diagnosed with acute myeloid leukemia (AML) inv16 (CBF-MYH11) with c-KIT mutation in July 2011. The patient underwent induction chemotherapy according to the DAC-7 protocol (Daunorubicin 60 mg/m^2/day i.v., days 1–3; Cytarabine 200 mg/m^2/day, days 1-7; Cladribine 5 mg/m^2/ day, days 1-5) and complete hematological remission was achieved. Consolidation consisted of 2 cycles with high dose Cytarabine (HAM: Cytarabine 1.5 g/m^2/day i.v. D: 1-3; Mitoxantrone 10 mg/m2 D: 3-5 in September 2011 and HD-Ara-C: Cytarabine 2 g/m^2 i.v. D 1, 3, 5 in October 2011). Aplasia period, after second consolidation, was complicated by severe diarrhea with Clostridium difficile etiology. Molecular MRD was positive after induction and consolidation and the patient was qualified for matched related donor allogeneic hematopoietic stem cell transplantation (MRD alloHSCT). In January 2013, the patient was admitted to transplant unit and subjected to 10/10 MRD peripheral blood stem cells transplantation with reduced toxicity conditioning according to BuClo regimen (Busilvex 3.2 mg/kg/day i.v. D-5 to -2 and Clofarabine 30mg/m^2/day i.v. D-6 to -2). Hematological recovery was achieved (WBC>1,5×10^9/l on D+18, ANC>0.5×10^9/l on D+18, PLT>20×10^9/l on D+10, PLT >50×10^9/l on D+10). First chimerism analysis revealed completedonor chimerism, but molecular minimal residual disease (MRD) signal - CBF-MYH11 was positive. Because of high risk of relapse immunosupression was tapered and finally discontinued on D+120. In September 2012, 6 months after transplant, the patient developed dry cough and dyspnoea at exertion. Spirometry revealed severe obturation, there were no abnormalities in HRCT assessment. Bronchiolitis obliterates syndrome was diagnosed and the patient restarted systemic immunosuppression (Tacrolimus+steroids) collaterally with FAM (inhaled Fluticasone/Azithromycin/ Montelukast) and Posaconazole prophylaxis with good response. In March 2013 after respiratory tract infection the patient complained of prolonged productive cough and malaise. HRCT results and microbiological BAL culture (Aspergillus fumigatus) confirmed invasive pulmonary aspergillosis. Voriconazole treatment led to resolution of symptoms and typical abnormalities in imaging. In regular control of the asymptomatic patient in September 2015, 44 months after transplantation, molecular analysis revealed positive CBF-MYH11. With no abnormalities found both in CBC and bone marrow assessment, positron emission tomography (PET/CT) was performed and presented increased FDG metabolism in the region of left ovary. Surgically removed left ovary was enlarged 50x70 mm, hard, motionless with ovarian cavity and lateral wall of the uterus. In histopathology, ovary was massively infiltrated by atypical cells with morphology of blasts. In subsequent peripheral blood MRD molecular analysis was still positive and PET/CT revealed increased FDG metabolism in the left side of lower intestine. The patient was subjected to colonoscopy with biopsy. There was no pathology on inspection and in histopathology nonspecific scanty lymphoid infiltrates were found. 2-month later, next PET/CT was performed and metabolically active areas of the descending colon 52x44x47 mm, SUVmax 7.2; on the border of descending colon and distal segment 29x32x36 mm SUVmax 6.2 and intestinal loops, right from the rectum 55x53x46mm SUVmax 8.8 were noted (Figure1A,1B). Second colonoscopy confirmed diagnosis of extramedullary AML relapse in large intestine. To minimize the risk of severe bleeding and perforation, therapy was started with Dasatinib 100 mg/day orally with 5-Azacytidine 75 mg/m^2 for 7 days used off-label followed by systemic chemotherapy: Cytarabine 200 mg/m^2/day (1-5) + Idarubicine 12 mg/m^2/day (1-3) and 90%-regression of infiltrate was achieved, confirmed by PET/CT with negative molecular MRD. Double induction was planned, and the patient was subjected to 2nd course - Cytarabine 200mg/m^2/day (1-5) + Idarubicine 12mg/day (1-2). During aplasia, the patient developed fatal septic shock with Pseudomonas aeruginosa etiology and SIRS (Systemic Inflammatory Response Syndrome) and died in September 2016.

Citation: Mensah-Glanowska P, Glanowski D, Sporek-Kunicka A, Kviatkouskaya K, Szostek M, Piatkowska- Jakubas B, et al. Late Ovarian and Intestinal Extramedullary Relapse of Acute Myeloid Leukemia with Inv 16 after Allogeneic Hematopoietic Stem Cell Transplantation. Ann Hematol Oncol. 2018; 5(3): 1199.