ABSTRACT
With the recent discovery of CALR mutations, >80% of patients with myeloproliferative neoplasms carry a phenotype-driving mutation. For JAK2 V617F, the most frequent mutation in myeloproliferative neoplasms, accurate determination of mutational loads is of interest at diagnosis, for phenotypic and prognostic purposes, and during follow-up for minimal residual disease assessment. We developed a digital PCR technique that allowed the accurate determination of CALR allelic burdens for the main mutations (types 1 and 2). Compared with the commonly used fluorescent PCR product analysis, digital PCR is more precise, reproducible, and accurate. Furthermore, this method reached a very high sensitivity. We detected at least 0.025% CALR mutants. It can thus be used for patient characterization at diagnosis and for minimal residual disease monitoring. When applied to patients with primary myelofibrosis who underwent hematopoietic stem cell transplant, the digital PCR detected low levels of minimal residual disease. After negativation of the mutational load in all patients, the disease reappeared at a low level in one patient, preceding hematologic relapse. In conclusion, digital PCR adapted to type 1 and 2 CALR mutations is an inexpensive, highly precise, and sensitive technique suitable for evaluation of myeloproliferative neoplasm patients during follow-up.
Subject(s)
Bone Marrow Transplantation , Calreticulin/genetics , Hematopoietic Stem Cell Transplantation , Neoplasm, Residual/diagnosis , Polymerase Chain Reaction/methods , Primary Myelofibrosis/diagnosis , Alleles , Exons , Humans , Mutation , Neoplasm, Residual/genetics , Primary Myelofibrosis/geneticsABSTRACT
We performed a retrospective study to identify pretransplantation risk factors for steroid-refractory (SR) acute graft-versus host disease (aGVHD) after allogeneic stem cell transplantation from matched donors in 630 adult patients who underwent transplantation at our center between 2000 and 2012. The cumulative incidence (CI) of SR aGVHD was 11.3% ± 2.3%. The identified independent risk factors were matched unrelated donor (hazard ratio [HR], 2.52; P = .001), female donor for male recipient (HR, 1.84; P = .023) and absence of antithymocyte globulin (HR, 2.02; P = .005). Three risk groups were defined according to the presence of these risk factors. In the whole cohort, the CI of SR aGVHD was 3.5% ± 1.7% in the low-risk group (0 risk factor, n = 115), 9.3% ± 1.6% in the intermediate-risk group (1 risk factor, n = 323), and 19.3% ± 2.9% in the high-risk group (2 or 3 risk factors, n = 192). Our study suggests that pretransplantation characteristics might help identify patients at high risk for SR aGVHD. A risk adapted first-line treatment of aGVHD could be evaluated in those patients.
Subject(s)
Graft vs Host Disease/mortality , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Stem Cell Transplantation , Unrelated Donors , Acute Disease , Adolescent , Adult , Aged , Allografts , Female , Follow-Up Studies , Graft vs Host Disease/therapy , Humans , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that affects medium- and small-sized arteries. We report the case of a 32-year-old female with PAN in which renal involvement was revealed by a secondary hyperaldosteronism. Hypokaliemia and arterial hypertension preceded rupture of renal artery aneurysm by several months. We believe that hyperreninemia resulted from diffuse renal necrotizing vasculitis with occlusive but non-stenotic lesions. Angiography or CT scan should be performed systematically in PAN to screen for aneurysms so as to be able to consider prophylactic treatment by embolization and intensification of the general treatment. Hyperaldosteronism may reveal renal involvement in PAN and warrants an angiography if it has not yet been done.
