Allogeneic bone marrow transplantation for AL amyloidosis. B Guillaume1, N .... apies,5,6 whereas colchicine was ineffective.4 The reason for. 1978; 52: ...
Bone Marrow Transplantation, (1997) 20, 907–908 1997 Stockton Press All rights reserved 0268–3369/97 $12.00
Case report Allogeneic bone marrow transplantation for AL amyloidosis B Guillaume1, N Straetmans 1, M Jadoul2 , JP Cosyns3 and A Ferrant1 Departments of 1Hematology, 2 Nephrology and 3Pathology, Cliniques universitaires St Luc, Universite´ catholique de Louvain, Brussels, Belgium
AL amyloidosis is an infiltrative disorder characterized by the extracellular deposition of insoluble fibrillar immunoglobulin light chains whose production results from a plasma cell dyscrasia. Treatment with melphalan has resulted in an improvement in a few patients. Recently, intensive chemotherapy followed by autologous or syngeneic stem cell support has been shown to offer potential benefit. Allogeneic stem cell support after intensive therapy would retain the benefits of autologous transplantation, with the additional advantages of a tumor-free graft and of a possible graft-versus-tumor effect. We report a patient with AL amyloidosis and significant proteinuria. She improved after an allogeneic bone marrow transplantation. Keywords: amyloidosis; allogeneic BMT
Case report A 56-year-old woman noticed ankle oedema in November 1994. A superficial thrombophlebitis led to a blood test in January 1995. There was an increase in serum gammaglobulins (2.5 g/dl), with an IgG lambda monoclonal component (2.2 g/dl). The IgA concentration was 132 mg/dl, and the IgM 88 mg/dl. The serum creatinine was 0.8 mg/dl, and the blood count was normal. The serum albumin was 4.2 g/dl. Twenty-four hour proteinuria was 9.15 g. Analysis of the urinary proteins showed a mixed proteinuria, with an IgG lambda monoclonal immunoglobulin in the urine. Bone marrow examination showed 23% plasma cells, with membrane IgG lambda monoclonality. No amyloid deposition was seen in the bone marrow biopsy. The serum beta-2-microglobulin level was 2.3 mg/l, and serum CRP level ,0.2 mg/dl. Renal biopsy showed an infiltration of arteries and mesangium by eosinophilic deposits which showed the characteristic green birefringence under polarized light by Congo red stain. Immunofluorescence showed strong staining of the deposits by antilambda and anti-P component antisera, confirming the suspicion of AL amyloidosis. X-rays did not show bone
lesions, and magnetic resonance imaging of the bone marrow was normal. Electrocardiogram and echocardiography were normal. The patient had an HLA-identical sister. As first-line therapy, an allogeneic BMT was performed on 24 August 1995. Conditioning consisted of melphalan, 140 mg/m2, and TBI (800 cGy, single dose). GVHD prophylaxis included CsA and MTX. The immediate post-grafting period was uneventful. Grade I GVHD progressing to grade II developed on day 30 post-transplant. Methylprednisolone, 2 mg/kg/day for 10 days, followed by tapering of the dose, was effective. The monoclonal component was no longer detected in blood and urine on 25 October 1995. On 17 November 1995 the bone marrow was normal, without abnormal plasma cells and without B cell monoclonality on Southern blot analysis. There was full chimerism as demonstrated by RLFP. The proteinuria gradually decreased. At 18 months post-BMT, the proteinuria was 1.3 g/24 h (Figure 1), and there was no ankle oedema. Immunoelectrophoresis of the urine did not show a monoclonal band. At the time of writing, the performance status of the patient is 100%. There is limited chronic skin and liver GVHD, well controlled by CsA. The patient declined a repeat renal biopsy.
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Correspondence: Dr A Ferrant, Dept of Hematology, Cliniques universitaires St Luc, 10 avenue Hippocrate, 1200 Brussels, Belgium Received 23 May 1997; accepted 14 July 1997
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Months from BMT Figure 1
Evolution of proteinuria.
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Discussion In the patient we described, high-dose melphalan, TBI and a bone marrow allograft were followed by disappearance of the monoclonal serum component, clearing of the bone marrow plasmocytes and a marked improvement in proteinuria. The therapeutic procedure is likely to have been responsible for the clinical improvement. Clinical improvement in nephrotic syndrome has been observed both with conventional doses of melphalan1–4 and after dose-intensive therapies,5,6 whereas colchicine was ineffective. 4 The reason for the improvement in proteinuria is presumably the result of the arrest of abnormal plasma cell proliferation. Amyloid deposits may, however, persist despite the improvement in proteinuria induced by melphalan.2 As suggested by the favourable outcomes of our patient and of two patients reported by Comenzo et al6 dose-intensive therapy as first-line treatment for AL amyloidosis can be effective. Accordingly, patients could be spared the toxicities of other therapies. Allogeneic bone marrow is free of contaminating clonal cells and would render intensive therapy most efficient. To what extent a graft-versus-tumor effect, similar to that observed in multiple myleoma7,8 has been responsible for the improvement observed in the patient is, at this time, impossible to establish. The procedure is limited to patients with an HLA-compatible donor, and the complications of allogeneic BMT, especially GVHD, have to be kept in mind. These patients might also have impaired organ function, rendering them more prone to BMT-related toxicities.9,10 It remains possible that the long-term outcome of ABMT for amyloidosis will be equivalent to, or perhaps superior to the results of allogeneic BMT, because of a lower treatment-related mortality. Indeed, allografting in
multiple myeloma is associated with a higher treatmentrelated mortality than is autografting.11 References 1 Gertz M, Kyle RA, Greipp PR. Response rates and survival in primary systemic amyloidosis. Blood 1991; 77: 257–262. 2 Kyle RA, Wagoner RD, Holley KT. Primary systemic amyloidosis: resolution of the syndrome with melphalan and prednisone. Arch Intern Med 1982; 142: 1445–1447. 3 Kyle RA, Greipp PR. Primary systemic amyloidosis. Comparison of mephalan and prednisone versus placebo. Blood 1978; 52: 818–827. 4 Kyle RA, Gertz MA, Greipp PR et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. New Engl J Med 1997; 336: 1202–1207. 5 van Buren M, Hene RJ, Verdonck L et al. Clinical remission after syngeneic bone marrow transplantation in a patient with AL amyloidosis. Ann Intern Med 1995; 122: 508–510. 6 Comenzo RL, Vosburgh E, Simms RW et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients. Blood 1996; 88; 2801–2806. 7 Tricot G, Vesole DH, Jagannath S et al. Graft-versus-myeloma effect: proof of principle. Blood 1996; 87: 1196–1198. 8 Verdonck L, Lokhorst HM, Dekker AW et al. Graft-versusmyeloma effect in two cases. Lancet 1996; 347: 800–801. 9 Majolino I, Marceno R, Pecoraro G et al. High-dose therapy and autologous transplantation in amyloidosis-AL. Haematologica 1993; 78: 68–71. 10 Mehta J, Nagler A, Slavin S. Marrow transplantation in multiple myeloma (letter). New Engl J Med 1992; 326: 1087. 11 Bjo¨rkstrand B, Ljungman P, Svensson H et al. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective casematched study from the European Group for Blood and Marrow Transplantation. Blood 1996; 88: 4711–4718.
