Primary refractory B-cell lymphoblastic leukemia with extramedullary disease – a distinctive response to blinatumomab and inotuzumab ozogamicin

Silva, Wellington F; Marquez, Gabriel Lacerda; Salim, Rafael Calil; Rocha, Vanderson

doi:10.1016/j.htct.2018.11.004

Cited by 4 publications

(3 citation statements)

References 10 publications

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“… 27 EMD may involve different sites, as observed in our series. 28 , 29 The role of INO as treatment for patients with r/r ALL and EMD has largely not been studied. The randomized phase III INOVATE trial included only seven r/r ALL patients with EMD given INO treatment as well as five patients treated with standard-of-care chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and <i>BCR-ABL</i>-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

et al. 2022

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Acute lymphoblastic leukemia (ALL) can relapse in the extramedullary compartment, with or without medullary involvement. Response to treatment may be unique. We evaluated response to inotuzumab ozogamicin (INO) in 31 relapsed/refractory (r/r) BALL patients with extramedullary disease (EMD). Median age was 31 (range, 19-81) years. All patients were heavily pretreated, including allogeneic hematopoietic stem cell transplantation (allo-HCT; n=18). Overall response rate after two INO cycles was 84% (complete remission (CR), 55%; partial remission (PR), 29%; resistant disease (PD), 13%; early death, 3%). Median follow-up was 29 months and median overall survival (OS) 12.8 months. One-year and 2-year OS rates were 53% (95%-CI, 37-76%) and 18% (95%-CI, 8-43%), respectively. Age had no impact on OS when assessed as a continuous variable or dichotomized at 60 years. Twelve patients proceeded to allo-HCT (CR, n=6; PR, n=3; PD, n=3). Prior to allo-HCT, eight patients received ≤2 and four patients 3-4 INO cycles. Sinusoidal obstruction syndrome was reported in three patients, including one after transplant. Allo-HCT evaluated as a time-dependent variable had no impact on OS. INO seems to be effective as debulking strategy in r/r-ALL with EMD. However, INO followed by allo-HCT seems not to be effective in maintaining long term disease control.

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Section: Discussionmentioning

confidence: 99%

Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and <i>BCR-ABL</i>-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

et al. 2022

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“…27 EMD may involve different sites, as observed in our series. 28,29 The role of INO as treatment for patients with r/r ALL and EMD has largely not been studied. The randomized phase III INO-VATE trial included only seven r/r ALL patients with EMD given INO treatment as well as five patients treated with standard-of-care chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4

et al. 2022

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We retrospectively studied 125 patients with acute myeloid leukemia and trisomy 4 (median age at diagnosis, 58 years; range, 16-77 years) treated between 2000 and 2019 within a multicenter study. Trisomy 4 was the sole abnormality in 28 (22%) patients and additional abnormalities were present in 97 (78%) patients. Twenty-two (22%) and 15 (15%) of 101 tested patients harbored NPM1 and FLT3-ITD mutations. Two (3%) of 72 tested patients had double CEBPA mutations. Data on response to intensive anthracycline-based induction therapy were available for 119 patients. Complete remission was achieved in 67% (n=80) and the early death rate was 5% (n=6). Notably, patients with trisomy 4 as sole abnormality had a complete remission rate of 89%. Allogeneic hematopoietic cell transplantation was performed in 40 (34%) patients, of whom 19 were transplanted in first complete remission. The median follow-up of the intensively treated cohort was 5.76 years (95% confidence interval [95% CI]: 2.99-7.61 years). The 5-year overall survival and relapse-free survival rates were 30% (95% CI: 22-41%) and 27% (95% CI: 18-41%), respectively. An Andersen-Gill regression model on overall survival revealed that favorable-risk according to the European LeukemiaNet classification (hazard ratio [HR]=0.34; P=0.006) and trisomy 4 as sole abnormality (HR=0.41; P=0.01) were favorable factors, whereas age with a difference of 10 years (HR=1.15; P=0.11), female gender (HR=0.74; P=0.20) and allogeneic hematopoietic cell transplantation (HR=0.64; P=0.14) did not have an significant impact. In our cohort, patients with trisomy 4 as their sole abnormality had a high complete remission rate and favorable clinical outcome. Allogeneic hematopoietic cell transplantation did not seem to improve overall survival.

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“…Whereas CAR T-cell therapy may be somewhat effective in eradicating EM ALL, blinatumomab has not demonstrated a similar ability to induce remission in EM ALL due to either resistance to the drug or the emergence of a CD19-negative leukemia cell line [ 56 , 62 , 63 ]. A high disease burden and prior extramedullary disease have been associated with poor outcomes of blinatumomab use [ 64 ].…”

Section: Immunotherapy and Transplantation In The Setting Of Emrmentioning

confidence: 99%

Cardiac Relapse of Acute Lymphoblastic Leukemia Following Hematopoietic Stem Cell Transplantation: A Case Report and Review of Literature

Sheikh

Ragoonanan

Franklin

et al. 2021

Cancers

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Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) occurs in soft tissues and various organs outside the testis and central nervous system. Treatments such as hematopoietic stem cell transplantation and more novel modalities such as immunotherapy have eradicated ALL at extramedullary sites. In some instances, survival times for relapsed ALL at these sites are longer than those for relapsed disease involving only the bone marrow. Isolated relapse of ALL in the myocardium is rare, especially in children, making diagnosis and treatment of it difficult. More recent treatment options such as chimeric antigen receptor T-cell therapy carry a high risk of cytokine release syndrome and associated risk of worsening cardiac function. Herein we present the case of an 11-year-old boy who presented with relapsed symptomatic B-cell ALL in the myocardium following allogeneic hematopoietic stem cell transplantation. This is an unusual presentation of relapsed ALL and this case demonstrates the associated challenges in its diagnosis and treatment. The case report is followed by a literature review of the advances in treatment of pediatric leukemia and their application to extramedullary relapse of this disease in particular.

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Primary refractory B-cell lymphoblastic leukemia with extramedullary disease – a distinctive response to blinatumomab and inotuzumab ozogamicin

Cited by 4 publications

References 10 publications

Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and <i>BCR-ABL</i>-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and <i>BCR-ABL</i>-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4

Cardiac Relapse of Acute Lymphoblastic Leukemia Following Hematopoietic Stem Cell Transplantation: A Case Report and Review of Literature

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