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IACH NEWS OF THE WEEK |
February 16, 2026
Prepared by Dr Edwin Uriel Suárez |
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Unexplained Elevated Vitamin B12: Consider Macro-B12 [Retrospective study].
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Highlights: - Elevated vitamin B12 concentration can be caused by supplementation, liver disease, kidney disease, or myeloid malignancies. - A potential benign cause of this elevation is macro-B12, a complex of vitamin B12, transcobalamin, and immunoglobulins. Although not bioactive, this complex can cause elevated plasma vitamin B12 concentrations due to reduced clearance. - In patients with persistently elevated vitamin B12 concentrations and a low suspicion of a myeloid malignancy, polyethylene glycol precipitation may help to explain the elevated vitamin B12 and prevent unnecessary diagnostic procedures. The presence of macro-B12 was studied in a group of patients with and without myeloid malignancies. Macro-B12 was identified in 24% of 72 individuals with vitamin B12 >1476pmol/L. In one of these patients, a functional vitamin B12 deficiency was confirmed by an elevated methylmalonic acid concentration. Macro-B12 was not detected in 8 patients with a myeloid malignancy. |
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Retreatment with R-CHOP–like therapy in patients with late relapse of diffuse large B-cell lymphoma [Retrospective study]. |
Highlights: ● Late-relapse (>2 years from diagnosis) diffuse large B-cell lymphoma (DLBCL) is characterized by chemotherapy-sensitive disease, for which chemotherapy retreatment may be a reasonable option. ● A second course of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)–like therapy may result in durable remission in this population, avoiding the need for more intensive therapies. Sixty-five patients were identified; at relapse, the median age was 77 years (range, 52-89), 81% had stage III to IV DLBCL, 52% had an Eastern Cooperative Oncology Group performance status of 2 to 4, and 78% had an International Prognostic Index score of 3 to 5. The median time from original diagnosis was 7.4 years (range, 2.5-15.9). Median number of cycles of R-CHOP–like therapy (for example, etoposide is substituted for doxorubicin [R-CEOP]). Overall response rate was 72%, and complete response rate was 57%. With a median follow-up of 31 months (range, 3-193), median time to progression (TTP) was 45 months, 2-year TTP was 54%, 2-year progression-free survival was 46%, 2-year disease specific survival was 64%, and 2-year overall survival was 54%. Patients relapsing >5 years from diagnosis (n=51) had significantly better TTP than those relapsing between 2 and 5 years post diagnosis, with a 2-year TTP for very late relapse (≥ 5 years) of 66% compared with 9% for patients relapsing between 2 and 5 years (hazard ratio, 0.30; 95% confidence interval, 0.14-0.64; P=0.001). |
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2026 Update on the Management of Diffuse Large B-Cell Lymphoma [Review]. |
Key points: ● Diffuse large B-cell lymphoma (DLBCL) is the most common type of Non-Hodgkin lymphoma in the Western Hemisphere. ● It comprises a heterogenous group of 18 distinct types of large B-cell lymphomas, with different biology and clinical prognoses. DLBCL not otherwise specified is the most common type of large B-cell lymphoma. ● The clinical course of DLBCL tends to be aggressive, with survival typically measured in weeks to months without therapy. ● Multidisciplinary efforts have identified unique DLBCL subtypes by either cell of origin (COO) or molecular characteristics. These classification systems are now routinely used to identify subsets of patients with high-risk disease and poorer outcomes to up-front standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy. Currently, DLBCL subtype classification remains based on COO and genetic abnormalities. Gene expression profiling remains the gold standard to determine COO but is not currently feasible in routine clinical care. ● Rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) remains the backbone of therapy, and frontline therapeutic options in fit patients are polatuzumab-R-CHP and R-CHOP (O: Onvovin=vincristine), whereas elderly or frail/unfit patients may be treated with R-mini-CHOP or palliation. ● Frontline trials aim to improve outcomes for patients with high-risk disease utilizing R-CHOP + novel agents, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies. Trials in the elderly/unfit population are minimizing and omitting chemotherapy. ● Risk-adapted approaches targeting COO/molecular characteristics and utilizing interim positron emission tomography imaging or circulating cell-free DNA to guide therapy escalation or deescalation remain under investigation. ○ The optimal treatment of double-hit lymphoma and triple-hit lymphoma remains undefined. ● Second-line therapy curative-intent approaches include CAR T-cells or autologous stem cell transplantation, depending upon timing of disease progression after first-line therapy (Figure 1 in original paper). ○ The CD20 x CD3 bispecific antibodies, epcoritamab and glofitamab, were approved in the United States for third line and later therapy of DLBCL in 2023. ■ Glofitamab is administered intravenously for up to 1 year of treatment. Epcoritamab is administered subcutaneously and given as continuous dosing until progression or toxicity. ● In the relapsed/refractory setting, there has been a rapid growth in the therapeutic armamentarium, including bispecific antibody combinations with chemotherapy, bispecific antibodies with antibody-drug conjugates, and brentuximab vedotin + lenalidomide + rituximab. ● Multiple novel trials are further advancing the field away from chemotherapy including targeted therapy-antibody combinations, new bispecific antibodies and bispecific antibody combinations, immunomodulatory agents, and cellular therapy. |
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Clinical decisions in clonal hematopoiesis: a contemporary review for clinicians [Review]. |
Key points: ● Clonal Hematopoiesis (CH) is defined as the proliferation of hematopoietic stem and progenitor cells with somatic mutations in the absence of overt hematologic malignancy. CH is an age-related phenomenon, its prevalence increasing markedly with age, affecting up to 60% of people aged ≥ 80 years and up to 40% of healthy volunteers ≥ 50 years. ○ The variability in the reported prevalence of CH is mainly explained by the use of different sequencing platforms and variant call criteria. ● CH of Indeterminate Potential (CHIP) is defined by the presence of a somatic mutation in a hematological malignancy-associated driver gene (historically with a variant allele frequency [VAF] ≥ 2% ) in individuals without abnormal blood cell counts or overt hematologic disease. ● Age-Related CH describes the presence of any detectable CH associated with aging, irrespective of VAF, and encompasses clones with VAF below 2%. ● Micro-CH (or micro-CHIP) describes low-abundance clones identified through highly sensitive sequencing methods, typically with VAFs below the conventional 2% threshold used for CHIP. ● Myeloid CHIP (M-CHIP) specifically refers to CHIP with somatic mutations in myeloid neoplasm driver genes (e.g., DNMT3A, TET2, ASXL1, JAK2, TP53 ), which primarily increase the risk of myeloid malignancies. ● Lymphoid CHIP (L-CHIP) defined by recurrent somatic mutations that increase the risk of lymphoid malignancy. L-CHIP is often associated with mutations in genes such as PAX5, IKZF1, ID3, and NOTCH1. While some of these mutations are distinct to L-CHIP, mutations common in M-CHIP—like those in DNMT3A and TET2 —may also appear in the lymphoid lineage and impact its pathogenesis. ● Clonal Cytopenia(s) of Undetermined Significance (CCUS): Diagnosed when CH driver mutation is identified alongside one or more persistent (≥ 4 months) cytopenias that are otherwise unexplained by hematologic or non-hematologic conditions, and do not meet diagnostic criteria for defined myeloid neoplasms (MNs). ● Therapy-Related Clonal Cytopenia(s) of Undetermined Significance (t-CCUS): This term describes CCUS that develops in patients with CH following cancer therapies including chemotherapy, external radiation therapy, radioligand therapy, immunotherapy or cellular therapy, where CH clones tend to expand under therapeutic pressure and inflammatory conditions. ● Mosaic Chromosomal Alterations (mCAs) are large structural somatic mutations (greater than 1 megabase) involving gains (+), losses (-), or copy-neutral losses of heterozygosity (=) that cause CH. mCAs are a common type of clonal hematopoiesis. They can predispose to lymphoid malignancies such as chronic lymphocytic leukemia and MNs. mCAs often occur in conjunction with CH driver mutations, frequently causing bi-allelic alterations in the driver gene. ● Loss of X and Loss of Y (LoY) Chromosomes are specific types of sex chromosome mCAs, representing common forms of mCAs, and have been well-characterized and most frequently detected copy number alterations. In particular, LoY is associated with significantly worse overall survival and higher risk both of hematologic and solid cancers ● See Figure 1 in original paper for an algorithm for management of CH and CCUS. The algorithm guides clinicians through initial assessment, risk stratification based on mutation type and burden, and recommended surveillance strategies. |
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ASH 2026 Guidelines for Frontline Management of Acute Lymphoblastic Leukemia in Adolescents and Young Adults. |
Key points: ● Pediatric-inspired regimens containing asparaginase are recommended as frontline therapy compared to more traditional adult-inspired protocols, requiring significant supportive care and close follow up. ○ For adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) receiving frontline pediatric-inspired (asparaginase containing) regimens, the American Society Hematology (ASH) guideline panel recommends against the routine use of unfractionated heparin for venous thromboembolism (VTE) prophylaxis. ○ The ASH guideline panel determined that the evidence is insufficient to issue a recommendation for or against routine VTE prophylaxis with low molecular weight heparin or direct oral anticoagulants. ○ The evidence is insufficient to issue a recommendation for or against routine antithrombin replacement. ● Allogeneic hematopoietic stem cell transplantation (allo-HSCT) isn’t routinely recommended in first remission (CR1) but may be indicated for higher-risk subsets (especially those with minimal residual disease [MRD] persistence, induction failure, and high-risk biologic subsets). ● For AYAs with CD20-positive B-cell ALL receiving frontline therapy, the ASH guideline panel suggests the addition of rituximab to standard chemotherapy. ● For AYAs with B-cell ALL receiving frontline therapy, the ASH guideline panel suggests the addition of blinatumomab for those who achieve morphologic remission, regardless of MRD status. ● For AYAs with B-cell ALL receiving frontline therapy, the ASH guideline panel determined that the evidence is insufficient to issue a recommendation for or against the addition of inotuzumab. ● For AYAs with T-cell ALL receiving frontline therapy with all planned doses of asparaginase (including Capizzi methotrexate-based interim maintenance), the ASH guideline panel determined that the evidence is insufficient to issue a recommendation for or against the addition of nelarabine. ● For AYAs with T-cell lymphoblastic lymphoma receiving frontline therapy, the ASH guideline panel suggests against the addition of nelarabine, due to insufficient evidence demonstrating efficacy for nelarabine in these patients. ● For AYAs with T-cell ALL receiving frontline therapy, the ASH guideline panel suggests against the addition of bortezomib into treatment regimens. ● For AYAs with T-cell lymphoblastic lymphoma, the ASH guideline panel determined the evidence is insufficient to recommend for or against addition of bortezomib. ● For AYAs with Philadelphia chromosome-positive ALL, the ASH guideline panel suggests reduced-intensity therapy with tyrosine kinase inhibitor (TKI) for remission induction over intensive chemotherapy with TKI. This should be followed by post-remission therapy. Options include intensive chemotherapy + TKI and/or immunotherapy + TKI. Either of these approaches may be consolidated by allo-HSCT in CR1. ○ The panel recognizes that post-remission therapies (including allo-HSCT) are evolving given emerging data surrounding next-generation TKIs and novel/targeted immunotherapies. ● For patients with ALL with persistent MRD after ≥3 months of frontline therapy (induction plus a minimum of one block of post-remission therapy), the ASH guideline panel recommends a change in approach to treatment. ○ The change in therapy could include several approaches including immunotherapy or allo-HSCT. The optimal timing, choice of intervention(s), order, or combination of these approaches has not been defined. |
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