Chronic eosinophilic leukemia (CEL) is a rare myeloproliferative neoplasm characterized by sustained elevation of eosinophil counts greater than > 1.5 × 109/L in blood or bone marrow. Approximately 25-30% of patients with persistent hypereosinophilia have somatic mutations associated with myeloid neoplasms, and next generation sequencing has led to the use of newer treatments for CEL, including tyrosine kinase inhibitors (TKIs) such as imatinib. Before the advent of imatinib, the disease had a poor prognosis with a 5-year mortality close to 50%. However, in patients with CEL without the characteristic mutations, known as chronic eosinophilic leukemia, not otherwise specified (CEL-NOS), treatment options and guidance are limited. We present a case series of two CEL-NOS patients treated at our academic health sciences center.
Background:The 2024 International Myeloma Society-International Myeloma Working Group consensus classifies isolated elevated β2-microglobulin (β2M) with normal serum creatinine (SCr) as high-risk multiple myeloma (MM). However, creatinine-based renal definitions may be inaccurate in Asian populations with lower muscle mass. We aimed to evaluate the prognostic impact of isolated elevated β2M on overall survival (OS) using SCr- and Cockcroft-Gault-derived creatinine clearance (CrCl)-based definitions. Methods:This retrospective study included newly diagnosed MM patients (2006-2023). Patients were classified as group A (β2M < 5.5 mg/L), group B (β2M ≥ 5.5 mg/L, SCr < 1.2 mg/dL), or group C (β2M ≥ 5.5 mg/L, SCr ≥ 1.2 mg/dL). In secondary analyses, renal function was redefined using CrCl (≥ 60 mL/min). Results:Among 250 patients (mean age 61.0 ± 12.1 years; 62.0% male), 34.4% underwent autologous stem cell transplantation. Groups A, B, and C included 109 (43.6%), 29 (11.6%), and 112 (44.8%) patients, respectively. At a median follow-up of 4.55 years, 4-year OS for groups A, B, and C was 79.8%, 71.6%, and 60.0% (P = 0.015). Group B did not demonstrate significantly inferior OS compared with group A (adjusted hazard ratio (aHR), 1.51; 95% confidence interval (CI), 0.70-3.24), whereas group C had significantly worse OS (aHR, 1.79; 95% CI, 1.11-2.86). When renal function was defined by CrCl, reclassified group B (n = 19) showed significantly inferior OS (aHR, 2.61; 95% CI, 1.17-5.86). Conclusions:Isolated β2M elevation showed a trend toward inferior OS using the SCr-based definition. CrCl-based reclassification appeared to improve prognostic stratification by identifying occult renal impairment not detected by SCr alone. These findings require validation in larger studies.
Primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is a rare and aggressive subtype of diffuse large B-cell lymphoma (DLBCL). Classic Hodgkin lymphoma (HL), characterized by Reed-Sternberg cells, usually presents in supradiaphragmatic lymph nodes and spreads in a predictable pattern. While both are individually uncommon, the simultaneous presence of PCNSL and HL as a composite lymphoma (CL) is exceedingly rare and presents a unique therapeutic challenge. A 66-year-old male presented to the hospital with progressive neurological symptoms. Magnetic resonance imaging (MRI) revealed a brain mass, and biopsy confirmed it to be PC-NSL. Further staging with positron emission tomography-computed tomography (PET-CT) identified fluorodeoxyglucose (FDG)-avid cervical lymphadenopathy. Core needle biopsy of a cervical node demonstrated classical HL. As it is the more aggressive lymphoma, treatment for PCNSL was initiated first, with 10 cycles of methotrexate, rituximab, and temozolomide (MRT) targeting the central nervous system (CNS) lesion, followed by two cycles of high-dose methotrexate for maintenance therapy. Subsequent MRI of the brain revealed complete remission of PCNSL. The patient then received one cycle of nivolumab plus doxorubicin, vinblastine, and dacarbazine (Nivo-AVD) for HL, but treatment was discontinued due to intolerance. He was deemed to be a candidate for high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). To deepen remission of HL before transplant, he was given a single cycle of bendamustine. He subsequently underwent high-dose BCNU, etoposide, Ara-C, and melphalan (BEAM) chemotherapy followed by ASCT. The patient tolerated the transplant well. Subsequent MRI brain and PET-CT 4 months after transplantation revealed continued remission of PCNSL and resolution of his lymphadenopathy with a Deauville score of 1. He has remained in complete remission for 12 months, with no evidence of disease on follow-up imaging or neurological examination. CL involving PCNSL and HL are extraordinarily rare, with no established treatment guidelines. Our case illustrates the importance of addressing the more aggressive lymphoma first, in this case, PCNSL, while sequentially targeting HL. The treatment regimen resulted in a durable remission. Given the rarity of such cases, formal trials are unlikely; well-determined case reports remain vital in guiding management strategies.
Background: Langerhans cell histiocytosis (LCH) is a rare neoplasm with a heterogeneous clinical spectrum ranging from isolated lesions to multisystem disease, with recurrence reported in up to 50-60% of patients. Data on outcomes of recurrent LCH from resource-limited settings remain limited. Methods: We report a 12-year retrospective review of children (1-18 years) with biopsy-proven relapsed LCH treated between January 2014 and December 2025. Clinical characteristics, recurrence patterns, treatment, and long-term outcomes were analyzed. All patients had received first-line therapy according to LCH-III protocol. Salvage treatments included cladribine-based chemotherapy, lenalidomide-dexamethasone (Len-Dex), or surgery for isolated lesions. Follow-up was updated to December 31, 2025. Results: Seven patients with a median age of 22 months at diagnosis (range 6-57) were included. Four had risk-organ involvement at presentation. Diabetes insipidus was present in 4/7 (57%). The median time to first recurrence was 25.8 months (range 6-104). Recurrence involved bone alone in four patients and bone with skin in three patients; none had risk-organ involvement at relapse. Three patients experienced multiple recurrences. Salvage therapy included cladribinebased chemotherapy (n = 6), Len-Dex (n = 2), and surgery (n = 1). At a median follow-up of 114 months (range 63-169), overall and event-free survival were 100%. Long-term sequelae included persistent diabetes insipidus (3/4), sclerosing cholangitis (n = 1), and sensorineural hearing loss (n = 1). Conclusions: Children with recurrent LCH in this cohort demonstrated good long-term outcomes irrespective of the salvage treatment strategy. Len-Dex represents a feasible, cost-effective therapeutic option in resource-limited settings where access to targeted therapy is limited.
Background: Systemic light-chain (AL) amyloidosis is a life-threatening disorder with historically poor outcomes. Daratumumab is a newer treatment for AL amyloidosis, but real-world trends in diagnosis, treatment, and survival are not well characterized. Methods: We conducted a retrospective cohort study using the Tri-NetX Global Collaborative Network, identifying adults with AL amyloidosis from 2006 to 2025. To improve specificity, patients with concurrent multiple myeloma, and other common amyloidosis subtypes were excluded. Survival analyses were stratified by Boston University cardiac stages. Propensity score matching balanced demographics and comorbidities. Results: We included 43,878 patients. Survival was improved in 2016-2025 vs. 2006-2015 (hazards ratio (HR) = 0.75; 95% confidence interval (CI), 0.68-0.83). Stage II patients showed the most pronounced gains (1-year HR = 0.66, P = 0.020; 10-year HR = 0.77, P = 0.022; median overall survival (OS), 2,009 vs. 1,517 days). Stage IIIa/IIIb showed no decade-level improvement. In the daratumumab era (2021-2025 vs. 2016-2020), stage I demonstrated markedly superior 5-year survival (HR = 0.59; log-rank P = 0.001; median OS, 1,549 vs. 965 days), and stage IIIb showed 51% lower 5-year mortality (odds ratio (OR), 0.49; P = 0.043). Direct comparison of Dara-Cy-BorD vs. CyBorD (n = 59 matched pairs) confirmed superior survival (3-year HR = 0.33; log-rank P < 0.0001; median OS not reached vs. 694 days). Sensitivity analyses using unstaged patients and AL-specific International Classification of Diseases, 10th Revision (ICD-10) codes yielded consistent results. Conclusions: Real-world outcomes in AL amyloidosis improved across two decades, with declining mortality and therapeutic shifts following daratumumab adoption. Most improvements occurred post-2021, underscoring CD38-targeted therapy's transformative impact.
Dyskeratosis congenita (DC) is a rare inherited telomeropathy characterized by defective telomere maintenance and an elevated risk of hematologic malignancies. Classical Hodgkin lymphoma (cHL) is a rare malignancy described in patients with DC, and optimal treatment remains undefined due to overlapping toxicities of standard ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and radiation therapy in this high-risk population. We present a 48-year-old man with longstanding thrombocytopenia who was diagnosed with DC based on clinical features and genetic testing. Two years post diagnosis, he developed stage IIA bulky cHL (nodular sclerosing, CD30+, Epstein-Barr virus (EBV)+). To mitigate pulmonary and myelotoxicity risks, he received a modified regimen of brentuximab vedotin (BV) combined with adriamycin, vinblastine, and dacarbazine (BV-AVD), with full omission of bleomycin. Treatment complications included peripheral neuropathy resulting in BV dose reduction and vinblastine discontinuation. Worsening thrombocytopenia led to discontinuation of dacarbazine. Interim imaging showed tumor regression, with post-treatment positron emission tomography with computed tomography (PET-CT) confirming complete metabolic response. Involved-site radiotherapy was omitted to minimize long-term risks of skin malignancy, local skin reactions and poor skin healing, in the context of DC. Post-treatment bone marrow evaluation showed no evidence of myeloid malignancy or lymphoma. This case demonstrates that modified BV-AVD can achieve complete metabolic remission in DC patients with cHL, while managing significant treatment-related toxicities. It underscores the critical need for individualized therapy in patients with DC and supports careful consideration of radiation omission to reduce secondary malignancy risk. These findings provide a potential therapeutic framework for managing Hodgkin lymphoma in patients with DC.
Background:Chronic myeloid leukemia (CML) often presents with hematologic findings that overlap with reactive leukocytosis and other myeloproliferative neoplasms (MPNs), creating diagnostic uncertainty that may delay targeted therapy or prompt unnecessary molecular testing. Harlequin cells-abnormal eosinophils containing basophilic granules-are well described in acute myeloid leukemia (AML) with CBFB::MYH11 fusion, but their diagnostic relevance in CML has not been systematically assessed. Methods:We retrospectively reviewed 177 peripheral blood smears: 53 CML; 30 non-CML MPN and related disorders; 59 AML (including three with CBFB::MYH11 fusion); 11 eosinophilia; and 24 reactive cytosis cases. Harlequin cells were stringently defined as abnormal eosinophils containing both typical eosinophilic granules and large, distinctly basophilic (not purplish-orange) cytoplasmic granules to exclude reactive mimics. Results:Harlequin cells were identified in 72% (38 out of 53) of CML cases, a frequency significantly higher than in non-CML MPN (10%, P < 0.01), AML without CBFB::MYH11 fusion (3.6%, P < 0.01), eosinophilia (0%), and reactive cytosis (0%) groups. They were also observed in 67% (2/3) of AML with CBFB::MYH11 fusion and in 20% (3/15) of primary myelofibrosis, but were absent in polycythemia vera, essential thrombocythemia, and chronic myelomonocytic leukemia. Strictly defined Harlequin cells were not found in any reactive condition. Conclusions:In the appropriate clinical context, strictly defined Harlequin cells on routine peripheral blood smears may serve as a sensitive and highly specific morphologic clue for CML. Recognition of this readily accessible feature may facilitate prompt BCR::ABL1 confirmatory testing, reduce diagnostic ambiguity, and help avoid unnecessary ancillary studies.
Luspatercept is a novel erythroid maturation agent that has emerged as a significant advancement in the management of ineffective erythropoiesis. By targeting the transforming growth factor-β superfamily signaling pathway, Luspatercept enhances late-stage erythroid differentiation. This review provides an in-depth exploration of its mechanism of action, pharmacologic properties, and clinical efficacy across multiple hematologic disorders. We summarize trial outcomes in lower-risk myelodysplastic syndromes, transfusion-dependent β-thalassemia, and myelofibrosis, highlighting improvements in erythroid response and transfusion independence. The article also discusses adverse event profiles and future directions, including ongoing trials and potential expansion of indications. Luspatercept represents a promising targeted erythroid therapy with benefits across several hematologic diseases.
Background:Hypofibrinogenemia is a rare bleeding disorder characterized by excessive bleeding, impaired wound healing, and elevated perioperative risk. It most commonly results from pathogenic variants in the FGB gene. This study aimed to analyze the clinical phenotypes and genetic variants in a family with hypofibrinogenemia and explore its molecular pathogenic mechanisms. Methods:Fibrinogen (Fg) activity (Fg:C) was measured using the Clauss method and the prothrombin time (PT)-derived method, and Fg antigen (Fg:Ag) levels were determined by enzyme-linked immunosorbent assay (ELISA). Fg polymerization capacity was evaluated via a thrombin-induced Fg polymerization assay, and Fg levels and function were assessed using thromboelastography. Sanger sequencing was performed to screen for variants in all exons and flanking regions of the FGA, FGB, and FGG genes. Multiple in silico tools, including ClustalX-2.1-win, MutationTaster, PolyPhen-2, PROVEAN, I-Mutant 2.0 and Swiss-Pdb Viewer, were used to assess the conservation of the variation sites and their impact on protein structure and function. The pathogenicity of the variation sites was evaluated according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for the interpretation of sequence variants. Results:The proband and affected members exhibited prolonged thrombin time (TT), reduced Fg:C and Fg:Ag levels, and a hypocoagulable thromboelastography profile. Notably, Fg polymerization kinetics remained preserved, consistent with hypofibrinogenemia rather than dysfibrinogenemia. Genetic analysis identified a heterozygous missense variant FGB c.878G>T (p.Gly293Val) segregating with the phenotype. This variant was absent from population databases, located at a highly conserved residue, and predicted to be deleterious by multiple in silico tools. Protein structural modeling indicated local conformational disturbance. The variant was classified as likely pathogenic following the 2015 ACMG/Association for Molecular Pathology (AMP) standard guidelines. Conclusions:The FGB p.Gly293Val variant may cause a significant decrease in Fg:C and Fg:Ag by disrupting the structure and function of the Fg protein.
Background:CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9)-based gene editing represents a promising frontier for treating monogenic hematologic disorders. Several preclinical studies have demonstrated the transplantation efficiency of CRISPR-Cas9-mediated gene editing in hematopoietic stem and progenitor cells (HSPCs) using various animal models. Nonetheless, these studies have employed diverse gene-editing strategies, utilizing HSPCs from different origins and transplanting them into distinct mouse strains. The present study aimed to determine the optimum conditions for efficient engraftment of genetically modified HSPCs across various organs, thereby facilitating the translation of preclinical research into clinical applications. Methods:We conducted a comprehensive literature search using PubMed Medline, Web of Science, and Google Scholar for relevant articles published from 2014 to 2025 that evaluated the engraftment potential of CRISPR-Cas9 HSPCs in genetic disease models. A total of 39 studies met the inclusion criteria and were included in a meta-analysis using Jamovi software. Results:The study revealed a significantly reduced engraftment of gene-edited cells in the bone marrow, spleen, and peripheral blood in the pooled analysis. Subgroup analyses revealed that knockout cells exhibited diminished engraftment, whereas knock-in cells demonstrated engraftment levels comparable to those of their non-edited counterparts. No evidence of publication bias or substantial heterogeneity in the study design or outcomes was detected. Conclusions:Identifying the optimal parameters for gene editing to enhance engraftment efficiency may provide crucial insights for designing future clinical trials and advancing the therapeutic application of CRISPR-Cas9 edited HSPCs.
T-cell prolymphocytic leukemia (T-PLL) is a rare and clinically aggressive T-cell neoplasm, which is composed of lymphoid cells that are of post-thymic T-cell origin. This is a case of a 57-year-old female with no significant medical history, who presented with a 4-month history of facial swelling, peripheral edema, dyspnea, palpitations, and abnormal uterine bleeding (AUB). A complete blood count demonstrated lymphocytosis, and a computed tomography (CT) scan of the abdomen and pelvis showed diffuse lymphadenopathy, splenomegaly, and uterine fibroids. A bone marrow biopsy confirmed the presence of T-PLL with a subsequent endometrial biopsy showing atypical lymphoid proliferation consistent with T-PLL. The patient was started on alemtuzumab for T-PLL treatment. This case demonstrates a rare presentation of T-PLL with endometrial involvement, which may have contributed to the patient's postmenopausal uterine bleeding. Recognition and evaluation of disease infiltration require prompt clinical assessment to reduce the morbidity and mortality associated with T-PLL.
Background: Umbilical cord blood (CB) is an invaluable source of hematopoietic stem and progenitor cells (HSPCs). Its use in stem cell transplantation is however constrained by the insufficient cell dose present in each unit. Recent development in ex vivo HSPC expansion technologies addresses this issue and encourages the use of the best matched CB unit. In this study, we sought to develop a cryopreservation and thawing protocol for ex vivo expanded HSPC. Methods: CB CD34+ HSPC-enriched cells were expanded in serum-free medium supplemented with a previously optimized mix of chromatin-modifiers and early acting cytokines for 7-days. CB HSPC were then harvested and prepared for cryopreservation. Thawed CB samples were then analyzed by flow cytometry to measure cell viability and recovery of HSPC-enriched fractions, while graft potency was measured using the colony-forming unit (CFU) assay. Results: First, we compared two widely used means of freezing; a passive isopropyl alcohol-based freezing container vs. a controlled-rate freezer (CRF). Both methods exhibited comparable recovery of viable cell numbers, including the HSC-enriched CD34+CD45RA-CD90+ fraction, and similar potency measured using the CFU assay. Next, we compared two thawing methods frequently used in clinical settings. The "thaw and dilute" method slightly improved the recovery of total nucleated cells (TNC) and HSPC fractions over the "rinse" method, though potency was comparable between both thaw methods. Next, we investigated the impact of three different commercial freezing solutions on product recovery. Dimethyl sulfoxide (DMSO)/dextran-40 and CryoProtectPure-STEM (CPP) provided superior recovery of HSPCfractions and potency when compared to CryoScarless (CSL). Conclusions: Taken together, this study provides insights into alternative, less harmful options for the freezing and thawing of ex vivo expanded HSPCs.
Background: The aim of the study was to determine the interactive effect of age on overall survival (OS) and relative survival (RS) benefits of radiotherapy (RT) in early-stage diffuse large B-cell lymphoma (DLBCL). Methods: Data for 10,841 adults with early-stage DLBCL from the Surveillance, Epidemiology, and End Results database between 2002 and 2015 were retrospectively analyzed. Primary therapy was classified as combined-modality treatment (CMT; n = 3,631) and chemotherapy alone (n = 7,210). Inverse probability of treatment weighting was used to balance covariate distribution between the treatment groups. Survival was estimated and compared using the Kaplan-Mei er method and log-rank test, respectively. Age-RT interactive effect on survival was examined through Cox regression multiplicative interaction analysis. Results: Using age of 60 years as the reference, older age was an independent predictor of shorter OS in the multivariable Cox model (hazard ratio (HR), 1.07; 95% confidence interval (CI), 1.06-1.07; P < 0.001). After controlling for background mortality, older age was not an independent predictor of RS (HR, 1.00; 95% CI, 0.99-1.00; P = 0.842). Across all age groups, patients treated with CMT had better OS and RS than those who received chemotherapy alone. A significant interaction between age and RT was identified for both OS (Pinteraction = 0.020) and RS (Pinteraction = 0.038), indicating greater RT benefit in young patients. A linear correlation existed between RS and OS at the treatment arm level. Conclusions: RT was associated with improved net survival across all ages, particularly for young adults. RS was a valid alternative endpoint for prognostication and benefit evaluation.
Background:The aim of the study was to compare post-transplant cyclophosphamide (PTCY)-based regimens with historical regimens using calcineurin inhibitor and methotrexate (CNI-MTX) for allogeneic hematopoietic stem-cell transplant (HCT) in nonmalignant hematologic disorders. Methods:We conducted a single-center, retrospective review of patients with acquired severe aplastic anemia (N = 18) or Diamond-Blackfan anemia (N = 1) who underwent allogeneic HCT from 2011 to 2024. Patients received graft-versus-host disease (GVHD) prophylaxis with either CNI-MTX or PTCY-mycophenolate mofetil-tacrolimus. Primary endpoints were overall survival (OS) and disease-free survival (DFS) without graft failure at 1 year after transplantation. Results:In the CNI-MTX cohort (N = 14) with severe aplastic anemia, 11 patients received fludarabine-cyclophosphamide-thymoglobulin (ATG)-total body irradiation (TBI), while three received cyclophosphamide-ATG allogeneic HCT. Donors were matched-unrelated (N = 7), matched-related (N = 6), or mismatched-unrelated (N = 1). Graft sources included bone marrow (N = 12) or peripheral blood stem cells (N = 2). One patient developed grade 3 skin acute GVHD, and none had chronic GVHD. There was primary graft failure (N = 6), stable mixed T-cell chimerism (N = 4), and 100% donor chimerism (N = 4). Four patients with primary graft failure underwent salvage second transplants at a median of 103 days (35-322) after the first transplant. Five patients with primary graft failure died at a median of 6 months (0.89-9.3) from the first transplant. The PTCY cohort (N = 5) included four patients with severe aplastic anemia and one with Diamond-Blackfan anemia. All underwent fludarabine-cyclophosphamide-ATG-TBI allogeneic HCT. Donors were matched-related (N = 1), matched-unrelated (N = 2), syngeneic (N = 1), or haploidentical (N = 1). Graft source was peripheral blood stem cells (N = 3) for matched-related, matched-unrelated, and syngeneic transplants, and bone marrow (N = 2) for haploidentical and matched-unrelated donor transplants. Donor chimerism was 100% (N = 3) and mixed chimerism (N = 2). All patients became transfusion-independent, and none developed GVHD or graft failure. The 1-year OS rate was 64.29% vs. 100%, the 1-year DFS rate was 57.14% vs. 100%, and the 1-year GVHD-free, graft failure-free survival (GRFS) was 50% vs.100% for the CNI-MTX and PTCY cohorts, respectively. Despite a trend toward better OS, DFS, and GRFS for PTCY, the OS, DFS, and GRFS time distributions were not statistically significantly different (P = 0.1448, 0.0919, and 0.0627, respectively). Conclusion:Allogeneic HCT with uniform conditioning of fludarabine-cyclophosphamide-ATG-TBI with PTCY GVHD prophylaxis is effective for adults with severe aplastic anemia or Diamond-Blackfan anemia across donor types (matched-related, syngeneic, matched-unrelated, haploidentical) and should be prospectively compared with historical regimens using CNI-MTX GVHD prophylaxis.
Background:The aim of this study was to define the relationships between mean corpuscular volume (MCV) and 12 clinical and laboratory variables in HFE p.C282Y (rs1800562)/p.H63D (rs1799945) compound heterozygotes. Methods:We retrospectively studied self-reported non-Hispanic white adult compound heterozygotes with transferrin saturation (TS) > 50% and serum ferritin (SF) > 300 µg/L (men) or TS > 45% and SF > 200 µg/L (women) who participated in primary care-based screening. In post-screening evaluations, we excluded participants with anemia, pregnancy, or medication use that increases MCV. We defined heavy alcohol intake as > 28 g/day in men and > 14 g/day in women. We determined associations of MCV with the following clinical and laboratory variables: age, sex, body mass index (BMI), diabetes, daily intakes of heme, non-heme, and supplemental iron, daily intakes of alcohol, swollen or tender second/third metacarpophalangeal (MCP) joints, reports of therapeutic phlebotomy, TS, and SF. Results:There were 74 participants (37 men, 37 women) of mean age 59 ± 12 (SD) years. Mean screening TS and SF were 65±13% and 529 ± 169 µg/L (men) and 59 ± 14% and 376 ± 195 µg/L (women). Post-screening values did not differ significantly. Mean MCV was 95.7 ± 4.0 fL. There was a negative correlation of MCV with BMI (P = 0.0488) and positive correlations of MCV with age (P = 0.0098), daily heme iron intake (P = 0.0333), and daily alcohol intake (P = 0.0113). Mean MCVs of 19 participants with and 55 without heavy alcohol intake were 97.8 ± 3.8 fL and 95.0 ± 3.9 fL, respectively; P = 0.0074). Linear regression on MCV confirmed positive associations with age (P = 0.0064) and daily alcohol intake (P = 0.0151). MCV was not significantly associated with sex, diabetes, daily intakes of non-heme and supplemental iron, swollen or tender second/third MCP joints, reports of therapeutic phlebotomy, TS, or SF. Conclusion:MCV in HFE p.C282Y/p.H63D compound heterozygotes with high iron phenotypes is positively associated with age and daily alcohol intake, after adjustment for other variables.
