Diagnostic Dilemma of JMML Coexisting with CMV Infection

Puri, Kriti; Singh, Parminder; Das, Rashmi Ranjan; Seth, Rachna; Gupta, Ritu

doi:10.1007/s12098-010-0355-z

Cited by 5 publications

(3 citation statements)

References 9 publications

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“…3 However, as this assay could test positive in certain viral infections, it is considered a sensitive but non-specific assay. 11 Moreover, differentiation between CMV-related disease and JMML in infants excreting CMV is sometimes difficult, 22, 23, 24 because clinical and laboratory findings of CMV infection can overlap with those of JMML. 11 …”

Section: Discussionmentioning

confidence: 99%

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Hasegawa

Bugarin

Giordan

et al. 2013

Blood Cancer Journal

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To diagnose juvenile myelomonocytic leukemia (JMML) is sometimes challenging, because around 10% of patients lack molecular abnormalities affecting Ras-MAPK (mitogen-activated protein kinase) pathway and other diseases such as cytomegalovirus infection can mimic clinical signs of JMML. In order to validate a phospho-specific flow cytometry assay assessing phospho-signal transducer and activator of transcription factor 5 (p-STAT5) as a new diagnostic tool for JMML, we examined 22 samples from children with JMML and 47 controls. CD33+/CD34+ cells from 22 patients with JMML showed hyperphosphorylation of STAT5 induced by sub-saturating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF). Using a training set of samples (11 JMML and 23 controls), we identified a threshold for p-STAT5-positive after stimulation with 0.1 ng/ml GM-CSF (17.17%) that discriminates JMML from controls. This threshold was validated in an independent series (11 JMML, 24 controls and 7 cases with diseases other than JMML) where we demonstrated that patients with JMML could be distinguished from other subjects with a sensitivity of 91% (confidence interval (CI) 59–100%) and a specificity of 87% (CI 70–96%). Positive and negative predictive values were 71% (CI 42–92%) and 96% (CI 82–100%), respectively. In conclusion, flow cytometric p-STAT5 profiling is a reliable diagnostic tool for identifying patients with JMML and can contribute to consistency of current diagnostic criteria.

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Section: Discussionmentioning

confidence: 99%

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Hasegawa

Bugarin

Giordan

et al. 2013

Blood Cancer Journal

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“…Estimates have shown that approximately 20 cases of JMML occur annually in Japan, with the median age at diagnosis being 2 years (2). A suspected case of JMML typically presents with non-specific constitutional signs and symptoms, such as fever, infection, pallor, bleeding, cough, poor weight gain, maculopapular rash, lymphadenopathy, moderate hepatomegaly, marked splenomegaly, leukocytosis, absolute monocytosis, anemia, and thrombocytopenia (3).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Juvenile Myelomonocytic Leukemia Underlying Ornithine Transcarbamylase Deficiency Safely Treated Using Hematopoietic Stem Cell Transplantation

et al. 2022

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Background:Juvenile myelomonocytic leukemia (JMML), which is predominantly found in infants, is a clonal abnormality of pluripotent hematopoietic stem cells and presents with the symptoms of both myeloproliferative tumors and myelodysplastic syndromes. Estimates have shown that ~20 cases of JMML occur annually in Japan. Ornithine transcarbamylase deficiency (OTCD), the most common among all urea cycle disorders (UCDs), occurs in 1 of 80,000 people in Japan.Case PresentationA 10-month-old infant who had fever, vomiting, and diarrhea for 2 days was referred to our hospital for the following abnormalities in blood tests: white blood cell count, 48,200/μL; hemoglobin, 9.0 g/dL; and platelet count, 135,000/μL. Bone marrow examination showed a nucleated cell count of 396,000/mm3 and blast cell count of 5.0%, as well as decreased mature granulocyte count and slightly myeloperoxidase stain-negative blasts but no monoclonal cell proliferation on May–Giemsa staining. Colony assay showed the proliferation of spontaneous colony and high sensitivity to granulocyte-macrophage colony-stimulating factor. Genetic analysis of peripheral blood mononuclear cells showed that the patient was positive for neuroblastoma RAS (NRAS) mutation. The patient was ultimately diagnosed with JMML. Approximately 170 days after his first hematopoietic stem cell transplantation (HSCT), the patient's JMML relapsed. Shortly after the recurrence, nausea, vomiting, hyperventilation, and decreased vitality were observed, followed by a decrease in the level of consciousness. The patient's ammonia level was 472 μmol/L. A test for seven different genetic mutations for the UCD showed the presence of c. 119G>A (amino acid change p. Arg40His). As such, late-onset OTCD was added to his diagnosis. Administration of sodium phenylacetate, l-arginine hydrochloride, and carnitine was continued following the diagnosis of OTCD, after which hyperammonemia was not observed. Regarding JMML relapse, HSCT was performed on day 405 after the first transplantation.ConclusionHyperammonemia should be considered a differential diagnosis when unexplained and non-specific symptoms occur during the treatment of hematologic malignancies. Patients should be tested for UCD as a cause of hyperammonemia, and treatment for hyperammonemia should be continued until the cause is identified. The patient shows normal developmental progress, has an intact neurological status, and has not experienced another hyperammonemia attack. His JMML has remained in remission for over 3 years.

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“…However, survival up to 57-64 % have been reported post allogeneic stem cell transplant (SCT) [5,6]. There is a paucity of outcome data for JMML from India [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Juvenile Myelomonocytic Leukemia in India: Cure Remains a Distant Dream!

Ramzan

Yadav²,

Dhingra³

et al. 2014

Indian J Hematol Blood Transfus

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There is paucity of outcome data regarding juvenile myelomonocytic leukemia from India. We report a series of eight children. Three had monosomy 7 and one had complex cytogenetics. One with Down's syndrome recovered spontaneously. Three refused therapy of whom only one is alive with disease. One died post chemotherapy. Three underwent allogeneic stem cell transplant after protracted delay with funds arranged from various governmental and non-governmental organizations. Of these two died (relapse-1 and intracranial bleed-1) and one is alive and disease free. In India, it's a milestone to reach transplant due to high cost and cure still remains a distant dream.

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Diagnostic Dilemma of JMML Coexisting with CMV Infection

Cited by 5 publications

References 9 publications

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Validation of flow cytometric phospho-STAT5 as a diagnostic tool for juvenile myelomonocytic leukemia

Case Report: Juvenile Myelomonocytic Leukemia Underlying Ornithine Transcarbamylase Deficiency Safely Treated Using Hematopoietic Stem Cell Transplantation

Juvenile Myelomonocytic Leukemia in India: Cure Remains a Distant Dream!

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