Bone Marrow Transplantation (2014), 1–5 © 2014 Macmillan Publishers Limited All rights reserved 0268-3369/14 www.nature.com/bmt

ORIGINAL ARTICLE

Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure R St Bernard1, L Chodirker1, E Masih-Khan1, H Jiang2, N Franke1, V Kukreti1, R Tiedemann1, S Trudel1, D Reece1 and CI Chen1 Numerous studies have reported the feasibility and safety of autologous SCT (ASCT) in patients with multiple myeloma (MM) and mild to moderate renal impairment, but there are limited data in dialysis-dependent patients. In this retrospective study, we reviewed the toxicities and efficacy outcomes of 33 MM patients with dialysis-dependent renal failure who underwent ASCT at our institution from 1998 to 2012. The most common grade 3 non-hematologic toxicities were mucositis (49%), infection (15%) and bleeding (6%). Atrial dysrhythmias (24%) and delirium (30%) of all grades were also common. Hematologic toxicities included febrile neutropenia (88%); and RBC and platelet transfusions were required by 71 and 100% of patients, respectively. Transplantrelated mortality (TRM) was high at 15%, predominantly caused by septic shock. Response to ASCT was at least VGPR (very good PR) in 50%, PR in 46.2% and stable disease (SD) in 3.8%. Median OS was 5.6 years, comparable to our overall institutional data. Overall, seven patients became dialysis independent. We conclude that ASCT can be an effective treatment for dialysis-dependent MM patients, with high response rates and survival. However, toxicities and a high TRM are observed indicating that further studies are needed to enhance the safety of this approach. Bone Marrow Transplantation advance online publication, 6 October 2014; doi:10.1038/bmt.2014.226

INTRODUCTION Numerous trials have demonstrated that autologous SCT (ASCT) is superior to chemotherapy alone in newly diagnosed patients with multiple myeloma (MM).1–3 Approximately 20–40% percent of patients with MM have renal impairment at the time of diagnosis and up to 2–3% of patients will require dialysis during their disease course.4–7 Although ASCT appears feasible and safe in patients with mild to moderate renal impairment,8–11 there are limited data in those with dialysis-dependent renal failure. Studies on patients with renal dysfunction undergoing ASCT include only a small subset of patients on dialysis.8,10,12–14 It is encouraging, however, that even in patients with severe renal failure, improvements in renal function following transplantation can be observed.9,15–17 Unfortunately, patients with renal failure appear to have higher rates of treatment-related toxicities and transplantrelated mortality (TRM) compared with patients without renal failure.9,11,13 In the dialysis-dependent population, it is unclear whether an incremental increase in risk exists and moreover, what patient, disease or treatment-related variables may predispose to this risk. The current study describes the toxicity and efficacy outcomes of a cohort of dialysis-dependent myeloma patients undergoing ASCT and examines variables that may correlate with these outcomes.

PATIENTS AND METHODS Patients Using a prospectively maintained transplant myeloma database, we identified 33 patients with advanced renal failure who were either dialysis dependent before transplant or required dialysis during ASCT (Table 1). All patients were transplanted at our institution from June 1998 to May

2012. Patient charts and the transplant database were reviewed for patient and disease characteristics, stem cell mobilization/transplant details, peritransplant toxicities and survival outcomes. Creatinine clearance rates were calculated using the Cockcroft–Gault equation.18 Patients with documented light-chain amyloidosis were excluded. Approval for review of these records was obtained from the University Health Network Research Ethics Board.

Induction therapy, stem cell mobilization and transplant details In preparation for transplant, all patients received induction therapy using various regimens (Table 2). At our institution, patients were eligible for transplant if they achieved at least stable disease (SD) with induction therapy. PBSC were mobilized with subcutaneous G-CSF 10 µg/kg/day and CY 2.5 g/m2 i.v. A target of 5 × 106/kg CD34+ cells was used (sufficient to support two transplants), though a minimum of 2 × 106/kg CD34+ cells were required to proceed to transplant. Transplants were performed as an inpatient procedure, using high-dose melphalan as the conditioning regimen. Dose reductions for melphalan were used at the treating physicians discretion (Table 2).

Transplant supportive care All patients received antiviral prophylaxis with acyclovir 400 mg p.o./i.v. q24h on admission. On day 1 post transplant, patients commenced antibiotic prophylaxis with one of the following quinolones: ciprofloxacin 500 mg p.o. q12h; levofloxacin 500 mg p.o/i.v. q24h; or moxifloxacin 400 mg p.o./i.v. q24h, until the granulocyte count was ⩾ 1 × 109/L or until another broad-spectrum i.v. antibiotic was started for febrile neutropenia. Fluconazole 400 mg p.o./IV was given after each dialysis. Patients received G-CSF 300 mcg s.c. daily from day +7 until ANC 41.5. Antiemetics including ondansetron and dexamethasone were used with the high-dose melphalan administration. Patients were routinely transfused for Hb o80 g/L or platelets o10 × 109/L.

1 Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada and 2Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Correspondence: Dr CI Chen, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Suite 5-220, Toronto, Ontario, Canada M5G 2M9. E-mail: [email protected] Received 21 October 2013; revised 23 July 2014; accepted 28 July 2014

High transplant toxicity in myeloma and dialysis R St Bernard et al

2 Table 1.

Table 2.

Patient and disease characteristics

Clinical characteristics Median age at diagnosis; years (range) Median age at transplant; years (range) Gender; male (%) Median time from diagnosis to ASCT; months (range) Multiple myeloma subtype IgG (%) IgA (%) IgD (%) Light chain only (%) Light-chain subtype: Kappa light chain (%) Lambda light chain (%)

Induction 55 (38–64) 56 (39–65) 25 (76) 8.5 (4–44)

19 3 1 11

(58) (9) (3) (33)

11 (33) 22 (67)

Drug(s)

Baseline laboratory testing (at time of ASCT) Median β2M;nmol/L (range) 1059 (7.5–7270)a Number of patients with β2M 4200 nmol/L (%) 24/31b(77) Median Hb at ASCT: g/L (range) 112 (76–155) Number of patients at ASCT with Hb o100 g/L 7 (21) 218 (115–506) Median platelet count at ASCT: x103cells/mm3 (range) 5 (1.3–12) Median ANC at ASCT: x103cells/mm3 (range)

Dialysis requirements Chronic hemodialysis ⩾ 3 × /week before ASCT (%) Chronic hemodialysis 1–2 × /week before ASCT (%) Intermittent hemodialysis initiated during ASCT (%)

650 (71–1600) 30 (91) 1 (3) 2 (6)

15 (45) 10 (30) 4 (12) 4 (12)

Mobilizationa CD34+ PBSC

Median (range) 6

CD34 cells mobilized (x10 cells/kg) Median number of days of PBSC collection by apheresis

8.87 (2.57–26.56) 2 (1–6)

Conditioning Drug Melphalan 200 mg/m2 Melphalan 140 mg/m2 Melphalan 160 mg/m2 + TBI

Number of patients (%) 20 (61) 12 (36) 1 (3)

Abbreviation: VAD = VCR, doxorubicin, dexamethasone. aAll patients were mobilized with CY and G-CSF, with the exception of one patient who received G-CSF alone.

28 (85) 3 (9) 2 (6)

Abbreviations: ASCT = autologous SCT; β2M = beta-2 microglobulin. a Normal values of β2M: age o50 years 9.38–21.36 nmol/L; age 450 years 12.03–27.20 nmol/L. bBeta-2 microglobulin values were unknown for two patients.

Response assessment Response to induction was defined as the best response achieved before ASCT. Response to transplantation was assessed at approximately 100 days post ASCT. Definitions of response and progression were based on modified European group for Blood and Bone Marrow criteria with the addition of a category for VGPR.19,20 Responses were categorized as CR if there was a disappearance of monoclonal protein in the serum and urine by electrophoresis and immunofixation, disappearance of any soft tissue plasmacytoma and o5% plasma cells in BM as well as normalization of the free light-chain ratio (0.26–1.65). Response was characterized as VGPR when the serum/or and urine M-component was detectable by immunofixation but not by electrophoresis, or ⩾ 90% reduction in the serum M-component plus a urine M-component o 100 mg per 24 h, or a 490% reduction in the difference between involved and uninvolved free light-chain levels. PR was defined as ⩾ 50% reduction in M-protein or ⩾ 50% reduction in free light chains, or ⩾ 50% decreased in the difference between involved and uninvolved free light chain. SD was defined as any response that did not meet criteria for CR/VGPR, PR, or progressive disease. Progressive disease is defined as an increase of ⩾ 25% from lowest response value of: serum M-protein (with absolute amount greater than 5 g/L) or difference between involved and uninvolved free light chain (with the absolute increase ⩾ 100 mg/L) or BM plasma cells.

Statistical analysis Descriptive statistics such as median, range and proportions were used to describe the patient population, toxicities, TRM, ASCT responses, OS and Bone Marrow Transplantation (2014), 1 – 5

Number of patients (%)

Induction regimen (n = 33) VAD High-dose pulse dexamethasone alone Bortezomib-based regimens Other

+

Renal function at myeloma diagnosis Median serum creatinine: µmol/L (range) Creatinine clearance o30 mL/min (%) Creatinine clearance 30–60 mL/min (%) Creatinine clearance 460 mL/min (%)

Details of induction, mobilization and conditioning

PFS. TRM was defined as any death within approximately 100 days of transplant. OS was calculated from the date of ASCT to the date of death due to any cause, with living patients censored on the last follow-up date. PFS was calculated from the date of ASCT to the date of progression or date of death; patients alive without progression were censored on the date of last follow-up. Survival estimates were calculated using the Kaplan– Meier method.21 In addition, we examined factors that may predict TRM/PFS/OS including age, gender, presence or absence of bone disease, percent BM plasma cells at diagnosis, MM subtype, time from diagnosis to transplant, melphalan dose, Hb, platelets and ANC at ASCT. Group differences of survival functions were examined using the log-rank test. All tests were two-tailed with Po0.05 considered statistically significant. P-values were not adjusted for multiple testing due to the exploratory nature of the study.

RESULTS Patient characteristics Patient characteristics are outlined in Table 1. All 33 patients had advanced renal failure, and the vast majority were dialysis dependent before transplant, 31/33 patients (94%), with 2/33 patients (6%) requiring repeated dialysis during ASCT hospitalization (Table 1). Dialysis-dependent patients required dialysis 1–3 times per week regularly before ASCT. One of the two patients who were not dialysis dependent before ASCT required threetimes weekly hemodialysis initiated on admission for ASCT, and continued thereafter. The other patient required dialysis only during ASCT. Most patients, 30/33 (91%), had a creatinine clearance of o 30mL/min at the time of myeloma diagnosis, with the vast majority of patients, 31/33 (94%), having no known renal impairment before MM diagnosis. One of the two patients who had pre-existing renal disease had a congenital single kidney and was on routine hemodialysis 10 years before MM diagnosis with the cause of renal failure not clearly determined. The other patient had a mildly elevated serum creatinine (130 µmol/L) 2 years before MM diagnosis but the etiology was not investigated at the time. All patients requiring regular renal replacement before © 2014 Macmillan Publishers Limited

High transplant toxicity in myeloma and dialysis R St Bernard et al

3 1.0

Response to induction and transplant Number of patients (%; N = 33)

Induction response CR/VGPR PR SD

7 (21) 16 (49) 10 (30) Number of patients (%; N = 26)a

ASCT response at 100 days CR/VGPR PR SD

13 (50) 12 (46) 1 (4)

Abbreviations: ASCT = autologous SCT; VGPR = very good PR; SD = stable disease. aTwenty-six patients were alive and eligible at time of assessment: two patients were lost to follow-up, five died with TRM

Progression free survival probability

Table 3.

Median PFS: 3.8 years 95% CI:1.9-6.6

0.8

0.6

0.4

0.2

0.0 0

Induction, stem cell mobilization and transplant treatment and engraftment details Details of induction regimens are shown in Table 2. A second induction was required in 6/33 (18%), and a third induction in 1/33 (3%) patients to achieve at least SD. Of the six patients requiring a second-induction regimen, five patients were progressing on treatment and one was not tolerating the treatment. One patient required a third induction due to progression while on treatment. The median number of induction cycles was 4 (range 2–13). Responses to induction therapy are shown in Table 3. Most patients (70%) achieved a PR or greater, with 30% achieving SD as best response. Details of stem cell mobilization are outlined in Table 1. All patients were able to mobilize adequate CD34+ cells on initial stem cell mobilization attempt. The median number of PBSC infused was 5.56 × 106 cells/kg (range 2.38–13.92 × 106 cells/kg). Most patients (61%) received full-dose melphalan 200 mg/m2 as the conditioning regimen; 39% received a reduced melphalan dose of 140 mg/m2 (n = 12) or 160 mg/m2 (n = 1). Median time for the engraftment of neutrophils was 12 days (range 10–15) and for platelets, it was 13 days (range 8–30). Transplant toxicity The most common non-hematologic toxicities (all grades) were mucositis (75%), delirium (30%) and atrial dysrhythmias (25%). The presentation of delirium included decreased level of consciousness, confusion, hallucination, paranoia and aggression. Neurological exam was unremarkable in all cases except for two cases where twitching/tremor was noted. In most cases, the onset of delirium coincided with the nadir of neutropenia on days 5–10 post ASCT and were felt to be related to concurrent medications (primarily morphine). Of note, 5/10 patients with delirium had a CT head, none of which showed acute changes, and only one showed mild cerebral atrophy and microangiopathic change. All cases of delirium resolved with the exception of one patient who died in the peritransplant period from septic shock shortly after the onset of delirium. Severe toxicities (grade 3–4) were mucositis (50%), infection (16%) and bleeding (6%). Febrile neutropenia occurred in most patients (88%), and documented infections included Streptococcus viridans bacteremia (n = 1), Clostridium difficile diarrhea (n = 1), candidemia (n = 1), Candida albicans pneumonia (n = 1) and herpes zoster (n = 1). Hematologic toxicities were © 2014 Macmillan Publishers Limited

2

3

4

5

6

7

8

9

Time (years)

Figure 1. PFS from transplant. The dashed line represents the 95% confidence interval (CI). The vertical lines along the solid line represents censored patients.

1.0

Overall survival probability

transplant were receiving hemodialysis, with no peritoneal dialysis modality used. Kidney biopsy results were available for 16/33 patients, and of those, 10 cases were reported as light-chain cast nephropathy, five as light-chain deposition disease and one case with both.

1

Median OS: 5.6 years 95% CI:1.9-NA

0.8

0.6

0.4

0.2

0.0 0

1

2

3

4

5

6

7

8

9

Time (years)

Figure 2. OS from transplant. The dashed line represents the 95% confidence interval (CI). The vertical lines along the solid line represents censored patients.

common with grade 4 neutropenia and thrombocytopenia reported in all patients with nadir data available (n = 31). Red cell and platelet transfusions were required by 71 and 100% of patients, respectively. Two patients (6%) developed grade-three bleeding events (hematemesis and epistaxis with gum bleeding).

Transplant-related mortality TRM was high at 15% (n = 5) and was attributed to septic shock in four cases (one candidemia, one CMV infection, two unknown sources) with one unknown cause of death. The five patients died at 8, 11, 36, 92 and 118 days post transplant. The patient who died of CMV at day 118 was included in our TRM analysis although it was outside our 100 day definition. The only variable reported to statistically correlate with TRM was response to induction. Four of the five TRM patients (80%) were able to achieve SD at best to induction versus PR or better (P = 0.011). Amongst the patients who did not succumb to TRM, only 40% achieved SD as their best Bone Marrow Transplantation (2014), 1 – 5

High transplant toxicity in myeloma and dialysis R St Bernard et al

4 response to induction, suggesting an association between reduced chemosensitivity and lower tolerance to toxicity. Transplant efficacy and survival outcomes Twenty-six patients were alive and eligible for response assessment at 100 days post ASCT. Response assessment at approximately 100 days post ASCT: 13/26 (50%) patients had achieved CR or VGPR; 12/26 (46%) patients PR; and 1/26 (4%) patients SD. At the time of data analysis (median follow up 3.8 years, range 0.3– 8.4 years post transplant), 50% of the patients who survived transplant had progressed with the median PFS of 3.8 years (range: 0.02–8.0 years; 95% confidence interval: 1.9–6.6; Figure 1). There was a statistically significant difference in PFS between patients with kappa versus lambda light chains, with a median PFS of 5.1 versus 2.1 years, respectively (P = 0.028). No other variable had a significant relationship to PFS. The median OS was 5.6 years (95% confidence interval: 4.2–not reached; Figure 2) and 5-year OS was 62.9% (95% confidence interval: 40.8–78.6). At the time of this analysis (median follow-up of 3.8 years), 15/33 (45%) had died. Similar to PFS, the only variable that showed a statistically significant relationship to OS was the light-chain subtype. OS in patients with kappa versus lambda light chains was of 7.5 versus 4.6 years, respectively (P = 0.038). Renal recovery Of the 28 patients who survived transplant, seven patients (25%) had an improvement in renal function and were able to discontinue dialysis. In three of these patients, dialysis was discontinued peritransplant before being discharged from hospital. In the other four patients, dialysis was discontinued at 3, 5, 9, 11 and 16 months post ASCT. With the exception of one patient, all the patients who had renal recovery were requiring regular hemodialysis 1–3 times/week before ASCT. These patients had been on dialysis for 3, 5, 5, 7.5, 8 and 8 months before transplant. None of the variables we investigated had a significant relationship to improvement in renal function. DISCUSSION The primary focus of this study was to report the toxicity and efficacy of ASCT in patients with MM and dialysis-dependent renal failure. We report an OS outcome of 5.6 years in this dialysisdependent cohort, comparable to the 5.2 years previously reported at our institution for all MM patients undergoing ASCT, regardless of renal function.22 Similar outcomes in non-dialysis populations have been reported by others.23–25 However, ASCT appears to carry increased risk of toxicity in dialysis-dependent patients with a predisposition to atrial arrhythmias, delirium, mucositis and bleeding, as noted in our cohort and supported by other studies.9,15 Interestingly, in the majority of patients with delirium, its onset coincided with the nadir of neutropenia. This suggests that this is a particularly vulnerable time in this population of patients and that transplant physicians should be particularly attuned to the signs of evolving delirium as neutropenia is worsening. This also highlights the importance of being vigilant about avoiding medications known to cause delirium if possible or adjusting medication doses to decrease the likelihood of delirium in patients with renal failure. In addition, TRM was higher in our study (15%) than previously reported by Badros et al.9 (2.6%) and Lee et al.15 (12%) after single transplant in dialysis-dependent patients. Although TRM in the study by Badros et al. was defined as death within 60 days of transplant versus 100 days in our analysis, this would not account for the differing rates, given that most TRM reported in our study occurred early. In our study, response to induction appeared to correlate with TRM; specifically, four out of five patients (80%) with TRM were only able to achieve SD before transplant. Badros et al. Bone Marrow Transplantation (2014), 1 – 5

similarly reported that refractory disease at autotransplant was one of the few variables that predicted increased early TRM.15 With regards to OS and PFS, patients producing light chains of lambda subtype had much shorter survival outcomes. Although similar findings are reported by others,26,27 our numbers are small and therefore require further validation. If confirmed, one might foresee the incorporation of response to induction and light-chain subtype into a risk-stratification approach for selection of dialysisdependent patients for transplantation. Of specific note, many patients in our study underwent induction with regimens such as VAD or high-dose dexamethasone alone (75%) that have been shown to be inferior to current regimens incorporating novel agents such as bortezomib and lenalidomide. We did not, however, note inferior survival outcomes anticipated with the use of inferior induction. Furthermore, given that these conservative regimens are less intensive and generally less toxic than three to four drug regimens in current use, it is unlikely that this impacted the high TRM observed in our patient cohort. As in other studies, we have shown that renal recovery is possible in patients with MM who undergo ASCT. In our study, of the 28 patients evaluable for renal function improvement, seven (25%) became dialysis independent. Our results are encouraging, though there is considerable variability in reported renal recovery from the literature (0–28%).9,10,14,15 On multivariate analysis, we were unable to identify any factors that could predict for renal recovery. In contrast, Lee et al.15 identified response (at least PR) to transplant and shorter duration of dialysis before transplant as predictive for renal recovery. Though our study is subject to the inherent limitations of a retrospective chart review, we are able to demonstrate that in patients with MM and dialysis-dependent renal failure, ASCT is feasible and can lead to similar survival outcomes to those without advanced renal failure. However, a higher rate of TRM and toxicities as reported in this analysis requires ongoing vigilance. Further studies are therefore needed in this population to evaluate patient selection and procedural details (that is, appropriate melphalan dosing, supportive and prophylactic measures) to enhance the safety of this approach. CONFLICT OF INTEREST Drs Kukreti, Tiedemann, Reece and Chen have received research funding and honoraria from Celgene and Janssen, Inc.

REFERENCES 1 Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. New Engl J Med 1996; 335: 91–97. 2 Barlogie B, Jagannath S, Desikan KR, Mattox S, Vesole D, Siegel D et al. Total therapy with tandem transplants for newly diagnosed multiple myeloma. Blood 1999; 93: 55–65. 3 Lenhoff S, Hjorth M, Holmberg E, Turesson I, Westin J, Nielsen JL et al. Impact on survival of high-dose therapy with autologous stem cell support in patients younger than 60 years with newly diagnosed multiple myeloma: a populationbased study. Nordic Myeloma Study Group. Blood 2000; 95: 7–11. 4 Blade J, Fernandez-Llama P, Bosch F, Montoliu J, Lens XM, Montoto S et al. Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution. Arch Int Med 1998; 158: 1889–1893. 5 Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol 2000; 65: 175–181. 6 Alexanian R, Barlogie B, Dixon D. Renal failure in multiple myeloma. Pathogenesis and prognostic implications. Arch Int Med 1990; 150: 1693–1695. 7 Clark AD, Shetty A, Soutar R. Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma. Blood Rev 1999; 13: 79–90. 8 Tosi P, Zamagni E, Ronconi S, Benni M, Motta MR, Rizzi S et al. Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure. Leukemia 2000; 14: 1310–1313.

© 2014 Macmillan Publishers Limited

High transplant toxicity in myeloma and dialysis R St Bernard et al

5 9 Badros A, Barlogie B, Siegel E, Roberts J, Langmaid C, Zangari M et al. Results of autologous stem cell transplant in multiple myeloma patients with renal failure. Br J Haematol 2001; 114: 822–829. 10 Parikh GC, Amjad AI, Saliba RM, Kazmi SM, Khan ZU, Lahoti A et al. Autologous hematopoietic stem cell transplantation may reverse renal failure in patients with multiple myeloma. Biol Blood Marrow Transplant 2009; 15: 812–816. 11 Knudsen LM, Nielsen B, Gimsing P, Geisler C. Autologous stem cell transplantation in multiple myeloma: outcome in patients with renal failure. Eur J Haematol 2005; 75: 27–33. 12 Carlson K. Melphalan 200 mg/m2 with blood stem cell support as first-line myeloma therapy: impact of glomerular filtration rate on engraftment, transplantation-related toxicity and survival. Bone Marrow Transplant 2005; 35: 985–990. 13 Ballester OF, Tummala R, Janssen WE, Fields KK, Hiemenz JW, Goldstein SC et al. High-dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma and renal insufficiency. Bone Marrow Transplant 1997; 20: 653–656. 14 Tosi P, Zamagni E, Tacchetti P, Ceccolini M, Perrone G, Brioli A et al. Thalidomidedexamethasone as induction therapy before autologous stem cell transplantation in patients with newly diagnosed multiple myeloma and renal insufficiency. Biol Blood Marrow Transplant 2010; 16: 1115–1121. 15 Lee CK, Zangari M, Barlogie B, Fassas A, van Rhee F, Thertulien R et al. Dialysisdependent renal failure in patients with myeloma can be reversed by high-dose myeloablative therapy and autotransplant. Bone Marrow Transplant 2004; 33: 823–828. 16 Tauro S, Clark FJ, Duncan N, Lipkin G, Richards N, Mahendra P. Recovery of renal function after autologous stem cell transplantation in myeloma patients with end-stage renal failure. Bone Marrow Transplant 2002; 30: 471–473. 17 Bird JM, Fuge R, Sirohi B, Apperley JF, Hunter A, Snowden J et al. The clinical outcome and toxicity of high-dose chemotherapy and autologous stem cell transplantation in patients with myeloma or amyloid and severe renal impairment: a British Society of Blood and Marrow Transplantation study. Br J Haematol 2006; 134: 385–390.

© 2014 Macmillan Publishers Limited

18 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41. 19 Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123. 20 Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473. 21 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481. 22 Prica A, Trieu Y, Xu W, Reece DE, Trudel S, Kukreti V et al. Rapidity and quality of response to steroid-based induction therapy, without the addition of novel agents, does not affect post transplant outcomes in multiple myeloma. Clin Lymphoma Myeloma Leuk 2013; 13: 25–31. 23 Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H et al. Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. J Clin Oncol 2012; 30: 2946–2955. 24 Rosinol L, Oriol A, Teruel AI, Hernandez D, Lopez-Jimenez J, de la Rubia J et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 2012; 120: 1589–1596. 25 Blanes M, Lahuerta JJ, Gonzalez JD, Ribas P, Solano C, Alegre A et al. Intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: a matched comparison to a melphalan-only approach. Biol Blood Marrow Transplant 2013; 19: 69–74. 26 Cornell CJ Jr, McIntyre OR, Kochwa S, Weksler BB, Pajak TF. Response to therapy in IgG myeloma patients excreting lambda or kappa light chains: CALGB experience. Blood 1979; 54: 23–29. 27 Shustik C, Bergsagel DE, Pruzanski W. Kappa and lambda light chain disease: survival rates and clinical manifestations. Blood 1976; 48: 41–51.

Bone Marrow Transplantation (2014), 1 – 5

Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure.

Numerous studies have reported the feasibility and safety of autologous SCT (ASCT) in patients with multiple myeloma (MM) and mild to moderate renal i...
360KB Sizes 2 Downloads 5 Views