Tuesday, February 24, 2015

Topic Discussion: MGUS and kidney transplantation

MGUS is defined as having a monoclonal protein in a small but abnormal concentration( <3g/dl). But the bone marrow doesn’t meet criteria for plasma cell percentage that qualifies for myeloma.  The incidence of MGUS is around 3.2% especially in the age >50 and the incidence rises as you age. Given the number of renal transplants are increasing especially in the age >50, it is evident that this entity comes up now frequently at transplant selection meetings.  What do we do? Is it a risk factor? Should we be worried?
MGRS( monoclonal gammopathy of renal significance) is a term now used to describe entities that have renal damage from MGUS. A recent KI paper sheds more light on the pathology of such cases. High rates of recurrence and the recurrence is early and more severe than in the native kidney. ( 40-60%) if MGUS had presented as MGRS( or some folks might want to call is MGKS).  Risk is especially high when there is a circulating Monoclonal immunoglobulins still around.  Recurrence is early and much more severe than the native disease.

Soltero et al. looked at transplant candidates with MGUS between 2000 and 2007 in a single center study.  MGUS that received a KT were compared with MGUS that were not transplanted.( similar age and CV risks) . Of 1215 KT candidates, 34 were found to have MGUS  (11%). The gammopathy was monoclonal in 76% of the cases. Nine patients with MGUS were transplanted. Following transplantation, the MGUS group had a lower survival than the non-transplanted group. (p = 0.0008).  Follow-up of 18.7 ±  15.4 months, seven patients (78%) died. Causes of death were cerebral abscess, lung cancer, sepsis, melanoma, bacterial meningitis, myocardial infarction. They had requested UNOS database from 1987-2003 and only found two reported cases of MGUS to UNOS.  Hence data might not be possible to be obtained from UNOS as not many centers are asking this information.
There are cases of LCDD, MPGN and proliferative GN with monoclonal deposits recurring after transplant. Most of the cases had untreated monoclonal clones prior to transplantation. They would now be classified as MGRS cases.

Is MGUS a risk factor for development of MM post transplantation?  A study from Mayo Clinic had indentified patients who had MGUS either before or after transplant. Of the 3518 patients who underwent transplantation, MGUS was found in 42 patients( 23 pre and 19 post).  They were followed for 8 years.  17% of pre transplant MGUS patients developed malignancies such as smoldering myeloma and other hematologic cancers.  None of the patients who developed MGUS post transplant progressed to MM.
Another more recent study by the Mayo group looked at newly diagnosed MM cases post transplantation. 7 cases were identified and 4 of them had MGUS pre transplant and two of them had clonal plasma cells in bone marrow. They concluded that MGUS prior to transplant was a risk factor for MM post transplant.

Garcia et al showed recently that MGUS following transplantation is a different phenomenon. It was  >100 times more frequent in transplant patients than in general population. Of their small subset of 11 patients with post transplant MGUS, only one developed PTLD.  In contrast to MGUS  in general population, progression to plasma cell dyscrasias was absent and it’s incidence is unknown A longitudinal study in 55 patients demonstrated that most of the MG reflected transient B-cell monoclonal proliferations, probably due to an immunodeficiency. Usually associated with intense immunosuppression and M protein is usually small and multiple bands.

In summary, MGRS may not be a contraindication to kidney transplantation as risk of dying from their clone is low.  No data to suggest that small B-cell clones are truly curable but there might be a high rate of recurrence in certain types. While LCDD and amyloidosis might have a slower recurrence rate, proliferative GN with monoclonal deposits might be must faster. MGUS might be a risk factor for development of active hematologic disease post kidney transplant.  The decision to transplant might depend on considering the underlying MGRS characteristics, initial therapeutic response, extrarenal manifestations, and the patient’s status. Risk of graft loss, its link with the B-cell clone and the potential need for reintroduction of chemotherapy should be explained to the recipient and the donor.

The field is still unsure on the question asked? 

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