Researchers Define Idiopathic Multicentric Castleman Disease with TAFRO Symptom


Release Subtitle:
Researchers develop internationally validated definition for iMCD-TAFRO disease, facilitating early diagnosis and better treatment

Release Summary Text:
A group of researchers from Okayama University, Japan, developed a definition for an aggressive subtype of the idiopathic multicentric Castleman disease (iMCD), which shows symptoms of thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) and validated the definition through the ACCELERATE Natural History Registry. This first ever definition of iMCD-TAFRO will go a long way in providing timely diagnosis and proper treatment for this rare, yet significantly aggressive disease.

Full text of release:
Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly, commonly known as TAFRO, is a set of heterogeneous symptoms that can manifest in patients suffering from infectious diseases, malignancies, and rheumatologic disorders. Thrombocytopenia refers to low blood platelet levels; anasarca is a medical condition leading to generalized swelling all over the body; reticulin fibrosis refers to replacement of bone marrow with fibrous tissue; renal insufficiency indicates improper functioning of kidneys; and organomegaly refers to enlargement of organs.

Interestingly, TAFRO symptoms are also very common in patients with idiopathic multicentric Castleman disease (iMCD), a rare medical condition associated with enlargement of lymph nodes. In fact, iMCD-TAFRO (iMCD with TAFRO symptoms) is considered to be a more aggressive subtype of iMCD, requiring special attention and additional therapies. Picking out iMCD-TAFRO from other iMCD cases early on is important for proper clinical treatment of patients. Unfortunately, despite the high mortality rate of iMCD-TAFRO, a globally validated definition of the disease is lacking, and so are established criteria to differentiate cases of iMCD-TAFRO from other iMCD cases.

This prompted a team of researchers led by Prof. Yasuharu Sato of Okayama University, Japan, to carry out a comprehensive review of iMCD-TAFRO cases and establish a validated definition for the disease. Their findings are published in the American Journal of Hematology. Explaining his motivation, Prof. Sato states, “We noted that in several patients suffering from TAFRO symptoms, clinical characteristics and response to treatment varied greatly. However, as there was no clear guidance available for defining iMCD-TAFRO, patients with iMCD showing TAFRO symptoms could not be treated properly.”

The team identified 54 cases of TAFRO from PubMed and Japan Medical Abstracts Society databases and classified them into three groups: Group 1 – iMCD-TAFRO (patients with TAFRO symptoms and confirmed iMCD diagnosis); Group 2 – possible iMCD-TAFRO (patients with TAFRO symptoms, but iMCD diagnosis not carried out); and Group 3 – TAFRO without iMCD.

Analysis of the data revealed that thrombocytopenia, anasarca, and fever were prevalent in all the 54 cases. Reticulin fibrosis was detected in 80–90% of the cases and all patients had some form of organomegaly. With respect to renal insufficiency, Group 1 showed 26.9% cases, Group 2 showed 54.5% cases, and Group 3 showed 50% cases. Further pathological analysis showed that serum immunoglobulin (antibody) levels were in the low- to mid-range and while serum alkaline phosphate (ALP) levels – used to detect liver or bone disorder – were elevated in Group 1 and 2. Additionally, the team also examined biopsy record for the cases and found that almost 89% of the cases had bone marrow biopsy and 80% had lymph node biopsy.

Based on their observations, the team developed a definition including 4 clinical criteria (thrombocytopenia, anasarca, fever, and organomegaly) and instances of renal failure or fibrosis in bone marrow or biopsy. The proposed definition was presented to the patient-powered arm of the ACCELERATE Natural History Registry (registry for Castleman disease patients) to examine how many patients fit the definition. Evaluation of medical records of 68 patients of iMCD from the United States of America (USA) revealed that 36 cases met the proposed definition for iMCD-TAFRO. The fact that this definition of iMCD-TAFRO, developed using data from patients in Japan, was able to justify the medical records of patients from USA, established its international validity.

The effort of this team to develop the first ever definition of iMCD-TAFRO will go a long way in providing timely diagnosis and proper treatment for this rare, yet significantly aggressive disease. Hoping to bring a change with this study, Prof. Sato says, “There is common misunderstanding in the medical and academic community that iMCD-TAFRO and TAFRO syndrome are somewhat similar. We hope that the validated definition of iMCD-TAFRO developed by us will clear this misunderstanding and lead to better patient care.”

Release URL:

Validated international definition of the TAFRO clinical subtype of idiopathic multicentric Castleman disease
Journal: American Journal of Hematology

Contact Person: Yasuharu Sato
Dr. Yasuharu Sato is a Professor at the Department of Medical Technology (Pathology), Graduate School of Health Sciences, Medical School, Okayama University, where he has been employed at since 2007. His key research areas are pathology focusing on hematopathology and head and neck pathology, and his research focuses on Castleman disease, IgG4-related disease, immunodeficiency-associated lymphoproliferative disorders, and head and neck tumors.

Researchers define iMCD-TAFRO, setting a landmark for timely diagnosis and treatment for this disease.