scholarly journals B-cell acute lymphoblastic leukemia in an elderly man with plasma cell myeloma and long-term exposure to thalidomide and lenalidomide: a case report and literature review

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ryan B. Sinit ◽  
Dick G. Hwang ◽  
Prakash Vishnu ◽  
Jess F. Peterson ◽  
David M. Aboulafia
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Plasma Cell ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Second Primary ◽  
Plasma Cell Myeloma ◽  
Sequence Of Events ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Background The advent of the immunomodulatory imide drugs (IMiDs) lenalidomide and thalidomide for the treatment of patients with plasma cell myeloma (PCM), has contributed to more than a doubling of the overall survival of these individuals. As a result, PCM patients join survivors of other malignancies such as breast and prostate cancer with a relatively new clinical problem – second primary malignancies (SPMs) – many of which are a result of the treatment of the initial cancer. PCM patients have a statistically significant increased risk for acute myeloid leukemia (AML) and Kaposi sarcoma. IMiD treatment has also been associated with an increased risk of myelodysplastic syndrome (MDS), AML, and squamous cell carcinoma of the skin. However, within these overlapping groups, acute lymphoblastic leukemia (ALL) is much less common. Case presentation Herein, we describe an elderly man with PCM and a 14-year cumulative history of IMiD therapy who developed persistent pancytopenia and was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). He joins a group of 17 other patients documented in the literature who have followed a similar sequence of events starting with worsening cytopenias while on IMiD maintenance for PCM. These PCM patients were diagnosed with B-ALL after a median time of 36 months after starting IMiD therapy and at a median age of 61.5 years old. Conclusions PCM patients with subsequent B-ALL have a poorer prognosis than their de novo B-ALL counterparts, however, the very low prevalence rate of subsequent B-ALL and high efficacy of IMiD maintenance therapy in PCM should not alter physicians’ current practice. Instead, there should be a low threshold for bone marrow biopsy for unexplained cytopenias.

Novel EZH2 Mutation in a Patient with Second Primary B-Cell Acute Lymphoblastic Leukemia after del5q Myelodysplastic Syndrome

2017 ◽  
Vol 17 ◽  
pp. S349
Author(s):  
Sebastian Burgos Canales ◽  
Maria L. Fuente ◽  
Guillermo Montalban Bravo ◽  
Guillermo Garcia-Manero ◽  
Maria J. Mela Osorio
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Myelodysplastic Syndrome ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Second Primary ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Mechanism of IL-10 Protective Effect in Development of Childhood B Cell Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4075-4075
Author(s):  
Briana Fitch ◽  
Michelle L. Hermiston ◽  
Joseph L. Wiemels ◽  
Scott C. Kogan
Keyword(s):  
Immune Response ◽  
Acute Lymphoblastic Leukemia ◽  
Mouse Model ◽  
B Cell ◽  
Knockout Mice ◽  
Lymphoblastic Leukemia ◽  
Host Immune System ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood. While significant progress has been made in the treatment of B-ALL, the factors that influence the development of B-ALL remain poorly understood. Epidemiological studies have established a role of early childhood infections in altering leukemia risk. The focus of these studies has been on documenting the number and timing of infectious exposures; however, the role of host immune response to infections in B-ALL development is largely unknown. Low birth levels of the immunomodulatory cytokine interleukin 10 (IL-10) are associated with a 25 fold increased risk of developing childhood B-ALL. Mechanistically, IL-10 plays a critical role in controlling the neonatal immune response to infections. Together, these findings suggest that IL-10, an important regulator of host immune responsiveness, protects against childhood B-ALL. To establish whether loss of IL-10 has an impact on leukemogenesis, we crossed Il10 knockout mice to the TEL-AML1 (ETVX6-RUNX1I) Ckdn2anull mouse model of childhood B-ALL. ETV6-RUNX1 t(12;21) is the most frequent chromosomal translocation in childhood B-ALLand one-fourth of these leukemias are observed in combination with loss of the Cdkn2a locus. The leukemia incidence in TEL-AML1 Ckdn2anull mice is 60%, therefore this is a robust and clinically relevant mouse model of childhood B-ALL. We used this model to assess the role of IL-10 in leukemogenesis by following Il10 knockout TEL-AML1 Ckdn2anull mice for the development of disease in comparison with control IL-10 expressing TEL-AML1 Ckdn2anull mice. We found that Il10 knockout accelerated leukemogenesis in the presence of TEL-AML1. The cancer free survival of the IL-10 expressing TEL-AML1 Ckdn2anull mice (n=74) was 227 days, whereas the survival of IL-10 knockout mice (n=40) was reduced to 180 days (p<0.0005). These data support a causal role of low levels of IL-10 in the development of B-ALL and raise the possibility of using an IL-10 receptor agonist for leukemia prevention in children with high risk of B-ALL. Thus, IL-10 loss is a defect in the host immune system that accelerates childhood B-ALL development, potentially through modifying immune responses to infections. Studies to understand the mechanism of how low IL-10 levels interact with infections to influence leukemogenesis are underway. Disclosures No relevant conflicts of interest to declare.

scholarly journals Myelodysplastic Syndrome with Myelofibrosis Transformed to a Precursor B-Cell Acute Lymphoblastic Leukemia: A Case Report with Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ayed A. Algarni ◽  
Mojtaba Akhtari ◽  
Kai Fu
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Myeloid Leukemia ◽  
Lymphoblastic Leukemia ◽  
Review Of The Literature ◽  
Acute Leukemias ◽  
Allogenic Stem Cell Transplantation ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Acute Myeloid

Myelodysplastic syndromes (MDS) comprise a group of heterogeneous clonal hematopoietic cell disorders characterized by cytopenias, bone marrow hypercellularity, and increased risk of transformation to acute leukemias. MDS usually transformed to acute myeloid leukemia, and transformation to acute lymphoblastic leukemia (ALL) is rare. Herein, we report a unique patient who presented with MDS with myelofibrosis. Two months after the initial diagnosis, she progressed to a precursor B-cell acute lymphoblastic leukemia. She was treated with induction therapy followed by allogenic stem cell transplantation. She was alive and doing well upon last followup. We have also reviewed the literature and discussed the clinicopathologic features of 36 MDS patients who progressed to ALL reported in the literature.

ADAM28 overexpression regulated via the PI3K/Akt pathway is associated with relapse in de novo adult B-cell acute lymphoblastic leukemia

2015 ◽  
Vol 39 (11) ◽  
pp. 1229-1238 ◽  
Author(s):  
Xiao-Hui Zhang ◽  
Chen-Cong Wang ◽  
Qian Jiang ◽  
Shen-Miao Yang ◽  
Hao Jiang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Akt Pathway ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2471-2478 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
F Lampert ◽  
J Harbott ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Residual Disease ◽  
Short Pulse ◽  
Lymphoblastic Leukemia ◽  
Pulse Therapy ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

Abstract In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL- BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL- BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

scholarly journals Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 5 (17) ◽  
pp. 3436-3444
Author(s):  
Hasmukh Jain ◽  
Manju Sengar ◽  
Vasu Babu Goli ◽  
Jayashree Thorat ◽  
Prashant Tembhare ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Confidence Interval ◽  
B Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Optimal Number ◽  
Cell Transplant ◽  
Historical Cohort ◽  
Cell Acute Lymphoblastic Leukemia

Abstract The expression of CD20 in precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD20+ ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD)-negative status postinduction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD-negative complete remission in patients with high-risk ALL. Given bortezomib’s activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20+ precursor B-ALL. We conducted a phase 2 study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (aged &gt;14 years) with CD20+, Philadelphia-negative precursor B-ALL; bone marrow MRD negativity at the end of induction was the primary end point. From December 2017 through August 2019, a total of 35 patients were enrolled. End-of-induction MRD-negative status was achieved in 70.9% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD-negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, event-free survival and overall survival rates were 78.8% (95% confidence interval, 66-94) and 78.7% (95% confidence interval, 65.8-94), respectively. There was no significant increase in toxicity with bortezomib and rituximab compared with the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen was active and well tolerated in de novo CD20+ Philadelphia-negative precursor B-ALL. This trial was registered with the Clinical Trials Registry-India as CTRI/2017/04/008393(http://ctri.nic.in/Clinicaltrials).

scholarly journals B-cell acute lymphoblastic leukemia in patients with germline RUNX1 mutations

2021 ◽  
Vol 5 (16) ◽  
pp. 3199-3202
Author(s):  
Kathryn A. Six ◽  
Ulrike Gerdemann ◽  
Anna L. Brown ◽  
Andrew E. Place ◽  
Alan B. Cantor ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Index Patient ◽  
Hematologic Malignancies ◽  
Increased Risk ◽  
Platelet Disorder ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Familial Platelet Disorder

Abstract Germline RUNX1 mutations underlie a syndrome, RUNX1-familial platelet disorder (RUNX1-FPD), characterized by bleeding symptoms that result from quantitative and/or qualitative defect in platelets and a significantly increased risk for developing hematologic malignancies. Myeloid neoplasms are the most commonly diagnosed hematologic malignancies, followed by lymphoid malignancies of T-cell origin. Here, we describe the first 2 cases of B-cell acute lymphoblastic leukemia (B-ALL) in patients with confirmed germline RUNX1 mutations. While 1 of the patients had a known diagnosis of RUNX1-FPD with a RUNX1 p.P240Hfs mutation, the other was the index patient of a kindred with a novel RUNX1 variant, RUNX1 c.587C&gt;T (p.T196I), noted on a targeted genetic testing of the B-ALL diagnostic sample. We discuss the clinical course, treatment approaches, and the outcome for the 2 patients. Additionally, we describe transient resolution of the mild thrombocytopenia and bleeding symptoms during therapy, as well as the finding of clonal hematopoiesis with a TET2 mutant clone in 1 of the patients. It is critical to consider testing for germline RUNX1 mutations in patients presenting with B-ALL who have a personal or family history of thrombocytopenia, bleeding symptoms, or RUNX1 variants identified on genetic testing at diagnosis.

scholarly journals Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2471-2478 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
F Lampert ◽  
J Harbott ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Residual Disease ◽  
Short Pulse ◽  
Lymphoblastic Leukemia ◽  
Pulse Therapy ◽  
Intrathecal Therapy ◽  
High Dose ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL- BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL- BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

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