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NDT Advance Access originally published online on September 12, 2006
Nephrology Dialysis Transplantation 2006 21(12):3585-3588; doi:10.1093/ndt/gfl403
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A case of successful double sequential bone marrow and kidney transplantations in a patient with multiple myeloma

Rami Khoriaty1, Zaher K. Otrock1, Walid A. Medawar1, Raja B. Khauli2 and Ali Bazarbachi1

1Department of Internal Medicine and 2Department of Surgery, American University of Beirut-Medical Center, Beirut, Lebanon

Correspondence and offprint requests to: Ali Bazarbachi, MD, PhD, Director, Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut-Medical Center, PO Box 113-6044, Beirut, Lebanon. Email: bazarbac{at}aub.edu.lb

Keywords: case report; kidney transplantation; multiple myeloma; stem cell transplantation



   Introduction
Top
 Introduction
Case presentation
 Discussion
 References
 
Multiple myeloma (MM) is a plasma-cell malignancy that, in the United States, constitutes 1.1% of all malignancies, 13.8% of haematological malignancies and ~2% of cancer deaths [1]. The 5, 10 and 20-year survival rate for MM are 31, 10 and 4%, respectively [2]. Potential complications of MM include spinal cord compression, renal failure (RF), anaemia, fractures, increased rate of infections and others. In two large studies, the incidence of RF in patients with MM, defined by a serum (Se) creatinine (Cr) level >132.6 µmol/l, was found to be 29 and 31%, respectively [3,4].

We report a patient with MM and RF successfully treated with autologous peripheral blood stem cell transplantation (APSCT) followed by kidney transplantation (KT). We also review the literature for similar cases.



   Case presentation
Top
 Introduction
 Case presentation
Discussion
 References
 
In May 1998, a 48-year-old man was found to have a Se Cr of 176.8 µmol/l (normal 53–124 µmol/l). His medical problems included hypercholesterolaemia, hypertension and peptic ulcer disease. Work-up of his RF revealed non-selective glomerular proteinuria, monoclonal free {kappa}-light chain on urine immunofixation and mesangioproliferative glomerulonephritis on kidney biopsy. The patient was lost to follow-up until October 2000, when he presented with severe RF: Se Cr and Cr clearance were 468.5 µmol/l and 0.190 ml/s (normal 1.62–2.29 ml/s), respectively. His chemistry results revealed an elevated Se calcium level of 2.75 mmol/l (normal 2.125–2.625 mmol/l) and a high 24-h urine protein level at 0.8 g/l (normal 0.04–0.23 g/l). A skeletal survey revealed two lytic lesions, and bone marrow biopsy showed 15% plasma cells. Based on these findings, the patient was diagnosed with MM ({kappa}-light chain disease). He received three cycles of chemotherapy consisting of continuous infusion of vincristine, doxorubicin and dexamethasone (VAD) over 4 days, every 28 days. His third cycle was complicated by steroid-induced acute psychosis that required hospitalization.

In January 2001, the patient presented to the American University of Beirut-Medical Center for further management of his disease. On admission, his laboratory studies revealed: Se Cr, 256 µmol/l; potassium (K+), 5.8 mmol/l (normal 3.5–5.1 mmol/l); calcium, 2.08 mmol/l; total Se protein, 49 x 103 g/l (normal 60–83 x 103 g/l); ß-2 microglobulin, 8.24 mg/l (normal <2.7 mg/l); 24-h urine Cr, 0.8 x 10–3 kg (normal 0.6–2 x 10–3 kg) and 24-h urine protein, 1.77 x 10–3 kg. Se protein electrophoresis showed no evidence of monoclonal immunoglobulins. Urine protein immunofixation revealed polyclonal immunoglobulins with no evidence of monoclonal immunoglobulin. Bone marrow biopsy showed no significant pathological abnormalities, and a skeletal survey showed no evidence of punched out lesions. After extensive evaluation, the decision was made to proceed with APSCT. The patient was given a 4th cycle of VAD and then underwent stem cell mobilization, collection and cryopreservation. As the number of CD34 positive cells was deemed appropriate (>2 x 106), he received high dose melphalan (140 mg/m2) followed by APSCT in January 2001. His post-transplant course was complicated by increased Se Cr, hyperuricaemia and febrile neutropenia, all of which were managed accordingly. The patient was discharged home 13 days post-APSCT after full recovery and adequate engraftment. His Se Cr at discharge was 353 µmol/l. The patient was followed-up for re-evaluation of his disease status at day 100 post-APSCT and then yearly thereafter and was consistently found to be in complete remission until the present date (May 2006). His Se Cr reached 451 µmol/l. However, the patient had an acceptable K+ level and urine output and did not require dialysis. In early 2004, the patient's Se Cr increased to 796 µmol/l, and then progressively rose to 1158 µmol/l necessitating admission in July 2004 for work-up of his worsening RF. After an extensive evaluation, the patient underwent a living related donor kidney transplant from his human leukocyte antigen (HLA)-identical sister, 3.5 years after his APSCT. He was put on a triple immunosuppressive therapy (mycophenolate mofetil, tacrolimus and prednisone) following antithymocyte globulin induction. He underwent Tc 99m MAG-3 renal scan that showed normal renal flow and function of the transplanted kidney. The patient's course was uneventful and he was discharged 6 days post-operatively with a Se Cr of 88.4 µmol/l. The patient's primary disease (MM) is still in complete remission, with no signs of graft rejection and with normal renal function as shown by his last Se Cr level of 115 µmol/l, at last follow-up (May 2006).



   Discussion
Top
 Introduction
 Case presentation
 Discussion
References
 
In one study, the median Se Cr level of 1027 patients with MM was found to be 106.1 µmol/l (range 44.2–1626.6 µmol/l). Of these patients, 52% had a Se Cr ≥ 124 µmol/l, with only 19% having a Se Cr ≥ 176.8 µmol/l [5]. On the other hand, it was shown in other series that the percentage of patients with MM and RF requiring dialysis was only 2–3% [6,7]. The pathogenesis of RF in MM patients is thought to be due to light chain tubular damage causing what is known as ‘myeloma kidney’ [8], immunoglobulin tissue deposition leading to nephrotic syndrome [9,10] or tubular dysfunction causing an acquired Fanconi syndrome [11]. The probability of recovery of RF in MM is around 50% in patients with Se Cr < 354 µmol/l, vs <10% in patients with Se Cr > 354 µmol/l [3,6,12]. Three factors are prognostic of reversibility of poor renal function in MM: Se Cr < 354 µmol/l, Se calcium ≥ 2.88 mmol/l, and 24-h urine protein excretion <1 x 10–3 kg [12].

Though the issue is controversial, APSCT is not usually considered the preferred treatment modality of MM in patients with RF, because of the potentially serious toxicities of the high-dose therapy required pre-APSCT, and the wide variation of melphalan elimination pharmacokinetics that might necessitate dose adjustments in RF. In a retrospective study, patients with MM and RF at the time of APSCT had a transplant-related mortality rate of 29% compared with 4.1% in patients who had abnormal renal function at diagnosis but normal kidney function prior to APSCT [13]. Transplant-related mortality was influenced by the presence of anaemia (Hb < 9.5 g/dl), severity of RF (Se Cr ≥ 442 µmol/l) and performance status (Eastern Cooperative Oncology Group (ECOG) ≥ 3) [13]. However, multiple reports have suggested that patients with MM and RF might safely benefit from myeloablative therapy followed by APSCT [14,15]. In addition, the presence of RF was shown to have no influence on the condition of the stem cells collected or on engraftment in patients with MM [16].

Acute RF in APSCT occurs as a result of neutropaenia, sepsis, the use of nephrotoxic medications and haemolytic uraemic syndrome secondary to cyclosporine, among other rarer causes [17,18]. In addition, chronic RF following APSCT, also known as APSCT nephropathy, is a possible but a rare complication of APSCT. It occurs in 0.8–9.5% of patients undergoing APSCT [19]. RF, in the absence of identifiable causes, develops at a median of 9 months (4.5–26 months) following APSCT [19]. Additional causes of chronic RF in patients post-APSCT include radiation induced RF [20,21], cyclosporine, cyclophosphamide and iphosphamide-induced nephrotoxicity [22–24] and subacute or chronic microangiopathy [25,26].

In our patient's case, based on the known benefits of autologous transplantation, the relatively young age of our patient, his Se Cr level of <442 µmol/l and his good performance status, the final consensus was to proceed with APSCT. His renal function did not improve post-APSCT. His Se Cr level stayed stable at ~442 µmol/l until about 3 years post-APSCT, when it increased tremendously, necessitating intervention. Our patient did not receive total body irradiation, as he received an autologous APSCT. He was never treated with cyclosporine or cyclophosphamide, and he did not have findings of a microangiopathy post-APSCT. Thus, the RF in this case is unlikely to be due to APSCT-nephropathy. The most probable cause of RF progression after APSCT in our patient is hyperfiltration injury. Again, based on the young age of our patient and his good performance status, and as KT has become the treatment of choice for patients with end-stage RF [27], we proceeded with KT that was successfully achieved with no complications and with good renal function thereafter.

To our knowledge, ours is the fourth reported case of both APSCT and KT in a patient with MM [28–30], and the first case of KT following APSCT in MM (Table 1). Our case demonstrates the importance of an aggressive approach to patients with MM, even in patients with impaired kidney function who are often not considered for bone marrow transplantation. We encourage the reporting of similar cases in order to make more robust inferences and analysis about the prognosis of such cases.


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  		Table 1. Patients with MM who underwent both APSCT and KT

 
Conflict of interest statement. None declared.



   References
Top
 Introduction
 Case presentation
 Discussion
 References
 

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Received for publication: 31. 5.06
Accepted in revised form: 13. 6.06


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