Blinatumomab resistant clone presenting as mixed phenotype myeloid sarcoma causing cord compression

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S99-S100
Author(s):  
D S Dabrowski ◽  
E Wei

Abstract Introduction/Objective Blinatumomab is a monoclonal antibody directed against CD19/CD3 utilized for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) and for the treatment of B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥0.1%. Although Blinatumomab treatment has shown better overall survival, progression-free survival, and complete remission when compared to chemotherapy, most patients have a relapse and ultimately succumb to the disease. Interestingly, there are a number of cases reporting relapse in extramedullary places. The mechanisms for relapse in these unusual extramedullary sites are not well-understood. We herein report a case of a 20-year-old African American male with primary refractory Philadelphia-negative (Ph-) precursor B cell ALL with MLL rearrangement, who received treatment with Blinatumomab after achieving morphological remission with a pediatric-inspired regimen but found to be MRD +. Methods/Case Report A 20 year old African American male was found to have B cell precursor ALL. It was found to be Ph-. While initally receiving vincristine, prednisone, and aspariginase, the ALL proved to be refractory to treatment. Blinatumomab was used as second line therapy after the first failed remission. The patient remained with morphological response; however, remained MRD+ after three cycles of Blinatumomab. During the fourth cycle, the patient presented with back pain and lower extremity weakness. A spine MRI revealed an extradural mass in the thoracic spine causing cord compression. A thoracic laminectomy with partial removal of the mass, followed by radiation, was performed with improvement of symptoms. Pathology results of the extradural mass revealed a myeloid sarcoma with MLL rearrangement. Results (if a Case Study enter NA) NA Conclusion This case report demonstrates how patients treated with blinatumomab can have relapse in unusual extramedullary places. The possibility of leukemia manifesting in extramedullary sites should always be kept in mind by clinicians treating patients with Blinatumomab. The mechanisms of resistance against Blinatumomab are not well- understood and need further elucidation.

2020 ◽  
Vol 4 (4) ◽  
pp. 603-606
Author(s):  
Marina Boushra

Introduction: Malignancy is a rare cause of acquired torticollis in children, and spinal cord involvement from hematolymphoid malignancies is similarly unusual. Neurologic abnormalities may not be present on initial evaluation, and delayed diagnosis and treatment is associated with increased risk of permanent paralysis. Case Report: The author describes a case of isolated torticollis in a 2-year-old evaluated multiple times in the emergency department (ED) and outpatient settings. For her first three presentations, the patient had no associated neurologic abnormalities. She was discharged with return precautions and a presumptive diagnosis of viral infection/lymphadenitis. She later developed weakness of her left arm and was diagnosed with a B-cell lymphoblastic leukemia/lymphoma causing spinal cord compression. Conclusion: This case highlights the importance of continued comprehensive and meticulous physical examination in patients with repeat ED visits, as well as the value of detailed discharge instructions in mitigating diagnostic delays in these patients.


Blood ◽  
2018 ◽  
Vol 131 (14) ◽  
pp. 1522-1531 ◽  
Author(s):  
Nicola Gökbuget ◽  
Hervé Dombret ◽  
Massimiliano Bonifacio ◽  
Albrecht Reichle ◽  
Carlos Graux ◽  
...  

Abstract Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission after multiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase–polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (≥10−3) received blinatumomab 15 µg/m2 per day by continuous IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic stem-cell transplantation any time after cycle 1. The primary end point was complete MRD response status after 1 cycle of blinatumomab. One hundred sixteen patients received blinatumomab. Eighty-eight (78%) of 113 evaluable patients achieved a complete MRD response. In the subgroup of 110 patients with Ph-negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 54%. Median overall survival (OS) was 36.5 months. In landmark analyses, complete MRD responders had longer RFS (23.6 vs 5.7 months; P = .002) and OS (38.9 vs 12.5 months; P = .002) compared with MRD nonresponders. Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) and 3 patients (3%) had grade 3 or 4 neurologic events, respectively. Four patients (3%) had cytokine release syndrome grade 1, n = 2; grade 3, n = 2), all during cycle 1. After treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, a majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders. This study is registered at www.clinicaltrials.gov as #NCT01207388.


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