Bock, H. A.

Passweg, J.

Thiel, G.

Tichelli, A.

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Nephrol Dial Transplant (1993) 8: 1393-1394Case ReportIMephrologyDialysisTransplantation'Transient multiple myeloma' after intense immunosuppression in a renaltransplant patientJ. Passweg1, H. A. Bock1, A. Tichelli2 and G. Thiel1Division of 'Nephrology and 2Hematology, Department of Internal Medicine, Kantonsspital Basel, SwitzerlandKey words: monoclonal gammopathy; multiplemyeloma; renal transplantationIntroductionB-cell lymphoproliferative disease, especially largecell lymphoma, is a well-recognized complication ofimmunosuppression early after organ transplantation,whereas the incidence of multiple myeloma does notappear to be increased [1]. We wish to report a patientwho was diagnosed as having multiple myeloma duringintense immunosuppression after renal transplantation.All abnormalities, however, later disappeared afterreduction of immunosuppression.Subjects and methodsThe patient, a 51-year-old woman, had suffered from chronicglomerulonephritis since 1958. End-stage renal failure hadbeen reached in 1976 and maintenance haemodialysis wasbegun. A first cadaveric renal transplant was rejected underconventional immunosuppression with azathioprine andprednisone within 6 weeks in 1978. Since she developed hightitres of panel-reactive antibodies, she could not be retrans-planted for several years thereafter.In October 1990 she finally received a second cadaverickidney graft. Immunoelectrophoresis before transplantationwas normal. Because of her history of rejection and lymph-ocytotoxic antibodies, an intensified immunosuppressive regi-men was administered, consisting of 5 mg OK.T3 for 14 days,cyclosporin 400 mg daily from day zero, azathioprine2 mg/kg and methylprednisolone pulses for 3 days followedby 0.5 mg/kg of oral prednisone thereafter (Figure 1).Although the graft functioned well from the first day,biopsy-proven vascular rejection on day 23 required therapywith seven daily doses of 5 mg OKT3, and seven pulses ofmethylprednisolone. The retreatement was well toleratedexcept for diarrhoea and slight pancytopenia. The patienthad to be readmitted on day 40 because of an increase inserum creatinine, and subfebrile temperature, dyspnoea,and cough.Admission serum protein electrophoresis revealed biclonalgammopathy, IgG kappa and lambda. Bronchoscopy speci-mens stained positive for Pneumocystis carinii, whichprompted a therapy with co-trimoxazole. She was treatedfor suspected rejection with four additional steroid pulsesand 7 days of rabbit anti-thymocyte globulin (ATGFresenius) 2 mg/kg body weight. Serum IgG increased from8.1 g/1 at transplantation to 33.1 g/1 by day 57. Urineelectrophoresis was trace positive for the IgG kappa mono-clonal component. Bone marrow examination revealedplasma cell infiltrates of 30% (focally up to over 50%). Thesecells were polymorphic with atypical nuclei, some with blasticnuclear structure (Figure 2). A radiological work-up forosteolysis or organ infiltration was negative.A diagnosis of multiple myeloma was made and removalof the renal transplant was therefore considered. However,since graft function improved in response to the rejectionno Gammopathybiclonal Gammopathy0 2 411 I I I8 10 12weeks after transplantationE3LA^ MP pulsesCorrespondence and offprint requests to: Professor G. Thiel, LeiterAbteilung Nephrologie, Departement Innere Medizin, KantonsspitalBasel, CH-4031 Basel, Switzerland.Fig. 1. Course of the patient's disease (top) and administeredimmunosuppression (bottom). B.Wt. = body weight.11993 European Dialysis and Transplant Association-European Renal Association1394Fig. 2. Bone marrow smear with dense infiltrate of plasma cells.treatment, immunosuppression could be reduced (seeFigure 1) at week 13. At day 90 the clonal gammopathy haddisappeared. A repeat bone marrow at that time showed lessthan 5% plasma cells. Today, 18 months after transplanta-tion, her graft functions satisfactorily with a serum creatinineof 109 umol/1. Immunosuppression is maintained with 300 mgcyclosporin and 7.5 mg prednisone daily. Serum proteinelectrophoresis still shows no sign of clonal gammopathy.DiscussionIn summary, this patient developed clonal gammopa-thy after intense immunosuppression with OKT3 (totaldose 105 mg) and MP pulses in addition to the baselinemedication with prednisone, azathioprine andcyclosporin. Bone marrow examination disclosedpolymorphic infiltrates of plasma cells. By commonlyrecognized criteria the combination of > 10% plasmacell infiltrate and clonal gammopathy in serum or urineallows the diagnosis of multiple myeloma [2]. However,reduction of immunosuppression was followed by com-plete disappearance of all abnormalities.J. Passweg et alMultiple myeloma has only rarely been reportedafter renal transplantation [3], but clonal gammo-pathies are frequently encountered in transplantpatients [4]. Their reported incidence ranges between4 and 68%, depending on the organ transplantated,the timing of sampling, and the sensitivity of themethods used to detect clonality [5]. Not unexpectedlythe incidence appears to be greatest after bone marrowtransplantation [6] and may be least after renal trans-plantation [7]. Clonal gammopathy after transplanta-tion is often transient, and the quantity of clonalimmunoglobulin is generally small [4]. The cause ofpathological clonal expansion is believed to beimpaired control of B-cell clones by suppressor T cells,most probably due to immunosuppression [8].Spontaneous remissions have to our knowledge notbeen reported in multiple myeloma. Since there is nosharp distinction between monoclonal gammopathyand multiple myeloma, there may be a zone of dia-gnostic overlap. B-cell lymphomas after organ trans-plantation are well known and their disappearanceafter dose reduction of immunosuppressives has beenreported.The lesson to be learned from the present case isthat a transient plasma cell dyscrasia may present likemultiple myeloma in the setting of heavy immunosup-pression after organ transplantation. The alarmingfindings suggesting myeloma after OKT3 therapy maycompletely resolve simply by reducing immunosuppres-sion without sacrificing the transplant.References1. Penn I. The changing pattern of posttransplant malignancies.Transplant Proc 1991; 23: 1101-1103.2. Kyle RA. Plasma cell proliferative disorders. In: Hoffman R,Benz EJ, Schattil SJ, Furie B, Cohen HJ. Hematology BasicPrinciples and Practice. Churchill Livingstone, 1991,pp.1021-1038.3. Howard AD, Moore J, Tomaszewsky MM. Occurrence of mul-tiple myeloma three years after successful renal transplantation.Am J Kidney Dis 1987; 10: 147-150.4. Radl J, Valentijn RM, Haaijman JJ, Paul LC. Monoclonalgammopathies in patients undergoing immunosuppressive treat-ment after renal transplantation. Clin Immunol Immunopathol1985; 37: 98-102.5. Peest D, Schaper B, Nashan B et al. High incidence of monoclonalimmunoglobulins in patients after liver or heart transplantation.Transplantation 1988; 46: 389-393.6. Fischer AM, Simon F, Le Deist F, Blanche S, Griscelli C, FischerA. Prospective study of the occurrence of monoclonal gammo-pathies following bone marrow transplantation in young children.Transplantation 1990; 49: 731-735.7. Pollock CA, Mahony JF, Ibels LS et al. Immunoglobulin abnor-malities in renal transplant recipients. Transplantation 1989; 47:952-956.8. Stanko CK, Jeffery JR, Rush DN. Monoclonal and multiclonalgammopathies after renal transplantation. Transplant Proc 1989;21: 3330-3332.Received for publication 24.3.93Accepted 24.6.93

‘Transient multiple myeloma' after intense immunosuppression in a renal transplant patient

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