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Polish Archives of Internal Medicine Jun 2024
Topics: Humans; Imatinib Mesylate; Mastocytosis, Systemic; Pyrimidines; Female; Piperazines; Antineoplastic Agents; Benzamides; Male; Middle Aged; Syndrome
PubMed: 38640058
DOI: 10.20452/pamw.16730 -
EJHaem Apr 2024
PubMed: 38633112
DOI: 10.1002/jha2.893 -
Indian Journal of Dermatology,... Feb 2024
PubMed: 38595013
DOI: 10.25259/IJDVL_712_2023 -
Blood Advances Jun 2024Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic...
Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, β2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308μg/L vs 146μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.
Topics: Humans; Mastocytosis, Systemic; Prognosis; Registries; Male; Female; Middle Aged; Adult; Aged; Biomarkers; Tryptases
PubMed: 38593217
DOI: 10.1182/bloodadvances.2024012756 -
The Journal of Allergy and Clinical... Mar 2024Anaphylaxis is a common feature of patients with mastocytosis, particularly with Hymenoptera venoms. Hence, it is hypothesized that patients with mastocytosis may have...
BACKGROUND
Anaphylaxis is a common feature of patients with mastocytosis, particularly with Hymenoptera venoms. Hence, it is hypothesized that patients with mastocytosis may have an increased susceptibility to developing drug-induced anaphylaxis (DIA). Patients and medical practitioners are therefore concerned when there is a need to use various drugs. However, this issue has not been systematically investigated.
OBJECTIVE
To investigate the prevalence and clinical characteristics of anaphylaxis to various types of drugs among patients with mastocytosis.
METHODS
A retrospective study was conducted among 470 consecutive patients (18 years and older) with confirmed clonal mast cell diseases recruited from 2 independent mastocytosis reference centers. All patients underwent a comprehensive, individualized allergy workup with evaluation of the (self)reported drug hypersensitivity.
RESULTS
The overall prevalence of DIA was 6.3%, accounting for one-third of the confirmed drug hypersensitivity reactions. Nonsteroidal anti-inflammatory drugs were the most common elicitors of DIA (56%), followed by perioperative agents (23%) and antibiotics (13%). Anaphylactic reactions were severe in most cases, with 43% of patients experiencing hypotensive syncope. All drug-related hypersensitivity reactions occurred before mastocytosis was diagnosed.
CONCLUSIONS
The prevalence of DIA in mastocytosis tends to be higher than in the general population, but is overall low. However, its severity is more pronounced. Our results suggest that patients with mastocytosis with a previous reaction to drugs should undergo a thorough allergy workup. Well-tolerated drugs can be further used without specific precautions.
PubMed: 38556047
DOI: 10.1016/j.jaip.2024.03.040 -
Indian Dermatology Online Journal 2024
PubMed: 38550813
DOI: 10.4103/idoj.idoj_242_23 -
NPJ Genomic Medicine Mar 2024Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome...
Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.
PubMed: 38538628
DOI: 10.1038/s41525-024-00405-z -
Hematology Reports Mar 2024Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K...
Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K deficiency or liver disease. Isolated acquired FVII deficiency is a rare occurrence and has been associated with inhibitors or auto-antibodies. Here, we describe a patient with polycythemia vera who developed systemic mastocytosis and FVII deficiency simultaneously. FVII deficiency was not caused by inhibitors and improved with antineoplastic treatment. Acquired FVII deficiency has been reported in cases of sepsis, possibly due to proteolytic degradation induced by the activation of monocytes or endothelial cells. Malignancies have been shown to cause a depletion in circulating FVII through the direct binding of cancer cells. This case report suggests a potential association between SM associated with a hematological neoplasm (SM-AHN) and acquired FVII deficiency. Further evaluations are recommended in patients with systemic mastocytosis to gain a better understanding of the relationship between pathological mast cells and clotting factor concentrations.
PubMed: 38534884
DOI: 10.3390/hematolrep16010014 -
Frontiers in Allergy 2024Empty mast cell syndrome, also named post anaphylaxis mast cell anergy (PAMA), is a temporary state of loss of mast cell responsiveness after a severe immediate...
Empty mast cell syndrome, also named post anaphylaxis mast cell anergy (PAMA), is a temporary state of loss of mast cell responsiveness after a severe immediate hypersensitivity reaction. In this study, we describe a case of PAMA after accidental re-exposure to amoxicillin in a patient who developed severe anaphylaxis to this drug three days earlier in the operating room. To our knowledge, this report is the second to document this phenomenon.
PubMed: 38529125
DOI: 10.3389/falgy.2024.1366922 -
Leukemia Apr 2024We identified 71 patients with AdvSM (aggressive SM [ASM], SM with an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia...
We identified 71 patients with AdvSM (aggressive SM [ASM], SM with an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia [MCL]) in two national registries (DRST/GREM) who received an allogeneic hematopoietic cell transplantation (alloHCT) performed in Germany from 1999-2021. Median overall survival (OS) of ASM/SM-AHN (n = 30, 45%), SM-AML (n = 28, 39%) and MCL ± AHN (n = 13, 19%) was 9.0, 3.3 and 0.9 years (P = 0.007). Improved median OS was associated with response of SM (17/41, 41%; HR 0.4 [0.2-0.9], P = 0.035) and/or of AHN (26/43, 60%, HR 0.3 [0.1-0.7], P = 0.004) prior to alloHCT. Adverse predictors for OS included absence of KIT D816V (10/61, 16%, HR 2.9 [1.2-6.5], P < 0.001) and a complex karyotype (9/60, 15%, HR 4.2 [1.8-10.0], P = 0.016). HLA-match, conditioning type or transplantation at centers reporting above-average alloHCTs (≥7) had no impact on OS. Taking into account competing events at years 1, 3 and 5, relapse-related mortality and non-relapse mortality rate were 15%/23%, 20%/30% and 23%/35%, respectively. Irrespective of subtype, subsequent treatment response was achieved in 13/30 (43%) patients and was highest on midostaurin/avapritinib (7/9, 78%). We conclude that outcome of alloHCT in AdvSM is more affected by disease phenotype and treatment response prior to transplant than by transplant characteristics.
Topics: Humans; Mastocytosis, Systemic; Retrospective Studies; Leukemia, Mast-Cell; Hematopoietic Stem Cell Transplantation; Leukemia, Myeloid, Acute
PubMed: 38448757
DOI: 10.1038/s41375-024-02186-x