precursor B-lymphoblastic leukemia/lymphoblastic lymphoma (B-cell ALL)
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Introduction
Neoplasm of lymphoblasts committed to B cell lineage. Precursor B-cell lymphoblastic leukemia and lymhoblastic lymphoma are considered parts of a spectrum of a single biologic entity.
Etiology
- unknown
- genetic factor play a role
Epidemiology
- ~80 - 85% of acute lymphoblastic leukemias
- ~10% of lymphoblastic lymphomas
Pathology
- ~80% of acute lymphoblastic leukemia
- <20% lymphoblastic lymphoma
- extramedullary involvement is frequent in B-ALL, particularly to CNS, lymph nodes, spleen, liver and gonads.
- B-lymphoblastic lymphoma most frequently involves skin, bone, soft tissue and lymph nodes.
Microscopic pathology
- medium sized cells
- round/convoluted nuclei, inconspicuous nucleoli
- scant cytoplasm
- chromatin moderately condensed to dispersed
- coarse azurophilic granules in ~10% cases
- mitoses less frequent in bone marrow than in T cell ALL
Immunophenotype
- surface immunoglobulin -
- CD10 +/-
- CD13 -/+
- CD19 +
- CD20 -/+
- CD22 +/-
- CD24 +/-
- CD33 -/+
- CD34 +/-
- CD79a +
- TdT +
- HLA-DR +
Genetics
- t(1;14)(q21;q32) BCL9
- t(1;19) (q23;p13.3) PBX1/TCF3
- t(4;11) (q21;q23) AF4/MLL
- t(9;22) (q34;q11.2) BCR/Abl
- t(12;21) (p13;q22) TEL/AML1
- t(17;19) (q22;p13.3) HLF/TCF3
- t(8;9) (p22;p24) JAK2/PCM1
- inv(19)(p13;q13) TFPT/TCF3
- hypodiploidy/hyperdipoidy
Genetic alterations associated with favorable prognosis:
- hyperdiploidy 51 - 65 chromosomes
- t(12;21) (p13;q22) chromosomal translocation
Genetic alterations associated with moderate prognosis:
- hyperdiploidy ~ 50
- triploidy
- tetraploidy
Genetic alterations associated with unfavorable prognosis:
Clinical manifestations
- highly aggressive, potentially curable
- B-ALL:
- B-lymphoblastic lymphoma
- most frequently skin, bone and lymph nodes
- skin involvement may manifest as multiple nodules
- % lymphoblasts in marrow <25%
Laboratory
Management
- see acute lymphoblastic leukemia
- inotuzumab ozogamicin + dexamethasone induction therapy can result in complete remission in older adults with Philadelphia chromosome-negative precursor B-cell ALL
- induction therapy includes 2 or 3 cycles of inotuzumab ozogamicin + dexamethasone, followed by age-adapted consolidation (5 cycles), late intensification (1 cycle), & maintenance chemotherapy (up to 2 years)[5]
- intrathecal chemotherapy prophylaxis administered all treatment phases
- induction therapy includes 2 or 3 cycles of inotuzumab ozogamicin + dexamethasone, followed by age-adapted consolidation (5 cycles), late intensification (1 cycle), & maintenance chemotherapy (up to 2 years)[5]
- adult who have failed chemotherapy
- autologous transformed T-cells show promise[3]
- harvested T-cell transformed with a virus, to express CD19 on their surface are reintroduced to the patient
- the T-cells subsequetnly attack and kill the malignant B-cells[3]
- induced remission may allow patients to become eligible for bone marrow transplantation[3]
- same strategy applied to children with ALL[4]
- emergence of leukemic blasts not expressing CD19 associated with relapse[4]
- autologous transformed T-cells show promise[3]
More general terms
References
- ↑ Chan JK, Banks PM, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, Grogan TM, Harris NL, Isaacson PG, et al. A revised European-American classification of lymphoid neoplasms proposed by the International Lymphoma Study Group. A summary version. Am J Clin Pathol. 1995 May;103(5):543-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7741099
- ↑ WHO Classification Tumours of Haematopoietic and Lymphoid Tissues. IARC Press 2001
- ↑ 3.0 3.1 3.2 3.3 Brentjens RJ et al CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia. Sci Transl Med 20 March 2013 5:177ra38 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23515080 <Internet> http://stm.sciencemag.org/search?author1=Renier+J.+Brentjens&sortspec=date&submit=Submit
- ↑ 4.0 4.1 4.2 Grupp SA et al Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia. N Engl J Med. March 25, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23527958 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1215134
- ↑ 5.0 5.1 Stelljes M et al. Inotuzumab ozogamicin as induction therapy for patients older than 55 years with Philadelphia chromosome-negative B-precursor ALL. J Clin Oncol 2024 Jan 20; 42:273 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37883727 https://ascopubs.org/doi/10.1200/JCO.23.00546
Logan A. Innovating simpler and less toxic frontline management for adults with ALL. J Clin Oncol 2024 Jan 20; 42:250. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37883737 https://ascopubs.org/doi/10.1200/JCO.23.01726