Status:
Ready to upload
Record number:
2119
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
Most recent risk assessment for monoclonal gammopathy of undetermined significance (MGUS) (Council of Europe, 2022):
Monoclonal gammopathies of undetermined significance (MGUS) in the donor history: MGUS with accurate diagnosis and appropriate follow-up without progression to multiple myeloma or related disorders after a definite disease-free interval of 5-10 years may be considered for organ donation and be assumed to pose a low risk for transmission.
It might be reasonable to accept an organ donor with a pre-diagnosed MGUS, especially in cases of confirmed MGUS without progression where the diagnosis has been confirmed years before.
Time to detection:
In this series, 2 donors with MGUS (unknown at time of transplant) provided organs for 7 recipients who developed either lymphoplasmacytic lymphoma, extramedullary plasmacytoma (with bony involvement) or MGUS (monoclonal gammopathy of undetermined significance). Times to detection ranged from 14-36 months in individual patients.
Alerting signals, symptoms, evidence of occurrence:
Increased creatinine led to renal biopsy and detection of lymphoid infitrates. This also led to screening of other recipients from these donors and detection by electrophoresis showing monoclonal proteins.
Demonstration of imputability or root cause:
Microsatellite analysis of paraffin tissue samples.
Imputability grade:
3 Definite/Certain/Proven
Groups audience:
Keywords:
References:
Suggest new keywords:
Malignancy
Single Center Series
DBD/donation after brain death
Deceased donor
Kidney transplant
Liver transplant
Heart transplant
DNA typing
Microsatellite
MGUS (monoclonal gammopathy of unknown significance)
Plasmacytoma, extra medullary
Lymphoma, B cell, lymphoplasmacytic
Therapy discussed
Reference attachment:
Suggest references:
Felldin M et al. Donor monoclonal gammopathy may cause lymphoproliferative disorders in solid organ transplant recipients. Am J Transplant 2016; 16: 2676-2683
Note:
First review MN 8/8/23: We need several clones for this, kidney, liver and heart. Also, we need a separate clone for MGUS (for each of the organ transplant types) -- OK (EP)
Second review MCS 13/08/24: Agree. An one small comment for MN consideration, which is to add another conclusion of authors at the end of expert comments: It seems important to study the incidence of MGUS in
donors. Undiagnosed MGUS and/or lymphoproliferative disease in donors may be a risk factor for malignancy in SOT recipients ¿? Another comment is if we can add Lymphoproliferative disorders as keywords.
MN 8/18/24: It would be worthwhile to add the comment regarding donors; I am not so sure about adding lymphoproliferative disorders here. In the transplant setting, that term is pretty much used to refer to PTLD, either polymorphic or lymphomatous. PTLD is not really consdiered a donor transmitted disease (with the exceptions of "donor derived" disease from donor cell origin PTLD arising in the posttransplant setting, or as an infectious transmission in the case of an EBV positive to negative transplant).
Expert comments for publication:
The donors did not have pre-donation evidence of hematopoietic disease (e.g., no lymphadenopathy) and the detection of MGUS was retrospective, with monoclonal protein levels of 8 and 37 g/L. The tumors that arose in these recipients showed the same heavy and light chain patterns as the donors, and were of donor origin, typically showing first in the allograft, though not limited to these sites. These tumors are not to be confused with the EBV-related PTLDs that arise from different mechanisms and are typically of recipient origin in solid organ recipients. Allograft nephrectomies along with chemotherapy and reduced/discontinued immunosuppression were performed in 3 kidney recipients who survived; a fourth kidney recipient who refused allograft nephrectomy died of progressive disease. One liver recipient died of myeloma 48 months after transplant, the second liver recipient developed asymptomatic MGUS at 36 months. The heart recipient also developed an M-spike of donor type but this patient was also HHV8 positive and developed a primary effusion lymphoma (PEL) of recipient origin.
The authors note that risk factors for progression of MGUS to malignancy include M protein >15 g/L, or altered free kappa lambda ratio. They were not able to determine free light chain ratios in this case series due to the small amount of available serum, and suggested that storage of serum is an important tool to study the extent of this problem. They also note other rare reports in which donors with MGUS did not transmit disease to the recipients. They suggest that the incidence of MGUS in organ donors should be studied to define the risk of subsequent recipient disease.