Effect of high-dose melphalan and peripheral blood stem cell transplantation on renal function in patients with multiple myeloma and renal insufficiency: a case report and review of the literature

1999 ◽  
Vol 78 (4) ◽  
pp. 189-191 ◽  
Author(s):  
E. Reiter ◽  
P. Kalhs ◽  
F. Keil ◽  
W. Rabitsch ◽  
H. Gisslinger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Stem Cell ◽  
Case Report ◽  
Renal Insufficiency ◽  
Peripheral Blood Stem Cell ◽  
High Dose ◽  
Review Of The Literature ◽  
High Dose Melphalan ◽  
Blood Stem Cell Transplantation

Improved Prediction of Kidney Disease by Estimating Renal Function: Use in Multiple Myeloma Patients Treated with Standard Versus High-Dose Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5497-5497
Author(s):  
Martina Kleber ◽  
Truc Ngo ◽  
Gabriele Ihorst ◽  
Bernd Koch ◽  
Monika Engelhardt
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Stem Cell ◽  
Kidney Disease ◽  
Renal Impairment ◽  
Peripheral Blood Stem Cell ◽  
Risk Groups ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Blood Stem Cell Transplantation

Abstract Multiple myeloma (MM) is characterized by the expansion of clonal plasma cells, leading to bone disease, marrow insufficiency and renal impairment (RI). However, the influence of milder degrees of RI and chronic kidney disease (CKD) is less well defined which seems of importance especially in MM patients (pts). We have previously reported in 167 cancer pts that estimating the glomerular filtration rate (eGFR) as compared to serum creatinine (crea) or cystatin levels best defines certain risk groups: with decreased eGFR, pts demonstrated to be older, had a higher body mass index and various other risk factors, indicating that eGFR determines early stages of renal impairment (RI) and prognostically adverse risk groups (Blood2005;106:2250). In order to analyze the frequency and particularly mild RI in a homogenous pt group, we determined renal function in 131 MM pts receiving standard (Std; n=69) or high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (hd CTx; n=62). We determined the disease-stage, sex, age, performance status (Karnofsky index=KI) and number of concurrent diagnoses (CD). Moreover, serum crea and eGFR (estimated by the four-component “Modification of Diet in Renal Disease” (MDRD) equation: NEJM2006;354:2473) were assessed. We defined CKD according to the guidelines of the National Kidney Foundation/Kidney Disease Outcome Quality Initiative. Despite a median of only 3 CD (range; 0–9) and an almost normal KI (median: 90%; range; 40–100) of all pts, the median age in the Std vs. hd CTx group was significantly higher with 65 vs. 54 years (p<0.001, Wilcoxon 2sample test), respectively. More advanced disease, as defined as pt number with stage II/III disease by Durie and Salmon (D&S) were lower in the Std vs.hd CTx group (86 vs. 95.1%, respectively), but pts with D&S stage B disease were higher in the Std group with 20% vs. 8% in the hd CTx group. This led us to hypothesis, that due to advanced age and more stage B disease in the Std group, RI was more frequent in this pt group. Of note, the median serum crea levels were comparable with 0.9 in the Std vs. 0.7mg/dl in the hd CTx group. Nevertheless, substantial differences between Std. vs. hd CTx pts were detected with analysis of the pt percentages with an elevated crea (>1.1mg/dl) [39% vs. 13%], eGFR<60ml/min/1.73m2 [37% vs. 9.7%], number of CD≥3 [46% vs. 69%] and KI≥90% [48% vs. 68%] (p<0.05), leading to decreased odds ratios (OR) in the hd CTx group of 0.1 (95%CI 0.1–0.3) for age ≥60y, 0.2 (CI 0.1–0.6) for crea>1.1 and 0.2 (CI 0.1–0.5) for eGFR<60, and increased OR for KI≥90 of 2.3 (CI 1.1–4.7) and CD≥3 of 2.7 (CI 1.3–5.6) as compared to the Std group. Differences in RI with active vs. non-active MM disease for all pts and within Std and hd CTx pts were insignificant. These results highlight the importance of reliably detecting early RI in cancer pts and its potential clinical consequences. eGFR may prove a valuable marker to subgroup MM pts and important for their assessment. Future longitudinal analyses with inclusion of disease outcome will determine whether eGFR, compared to other measurements of renal dysfunction, can be used as a useful prognostic marker in MM.

Results of a Phase II Open-Label Trial of Bortezomib in Patients with Multiple Myeloma Who Have Undergone High-Dose Melphalan Therapy Followed by Autologous Peripheral Blood Stem Cell Transplantation and Failed to Achieve a Complete Response

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2780-2780
Author(s):  
Robert M. Rifkin ◽  
Gary Spitzer ◽  
Andrew Greenspan ◽  
John F. Schwerkoske ◽  
Romeo A. Mandanas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Complete Response ◽  
High Dose ◽  
New Treatment ◽  
High Dose Melphalan ◽  
Blood Stem Cell Transplantation

Abstract Multiple myeloma (MM) is the second most common hematologic malignancy. Presently, the majority of suitable MM patients who undergo high-dose melphalan therapy followed by autologous peripheral blood stem cell transplantation (PBSCT) fail to achieve a complete response (CR). This suggests that treatment options following autologous transplantation are needed. Moreover, there is a need to determine the optimal role of maintenance therapy following PBSCT in MM. Over time, Bortezomib (B) has been shown to be an active agent in the treatment of newly diagnosed, and relapsed or refractory MM. Therefore, the primary objective of this study was to determine the efficacy of B treatment after high-dose melphalan therapy followed by PBSCT in MM. Fifty patients (pts) were enrolled between March 2004 and November 2007, and 47 were evaluable (2 pts ineligible and 1 pt data pending). Pts received B 1.3 mg/m2 IV on Days 1, 4, 8, and 11 of each 21-day cycle. Pts were treated for 4 cycles or until evidence of disease progression or intolerable toxicity. If an improvement in response was noted after Cycle 4, pts could receive up to 4 additional cycles. To reduce the incidence of varicella zoster infection, antiviral prophylaxis (acyclovir 400 mg PO BID) was taken for the duration of the study. The median patient age was 56 years (range, 39–74), 82% were white, and 68% were male. The majority of pts (64%) had ECOG PS 0, 44% were Durie-Salmon Stage IIIA prior to induction therapy. Forty percent had symptomatic IgG-kappa multiple myeloma. Of all pts, 74% had a single transplant, while 24% had tandem transplants (2% [n=1 pt] data pending). Sixty-eight percent of pts had a PR and 18% had a MR following their transplant(s). While on study, pts received a median of 4 cycles (range, 2–8) of therapy with B. Efficacy results for the evaluable population are: CR 4%, unconfirmed (u) CR 4%, PR 21%, uPR 17%, MR 11%, and No Change 36%. Median time-to-treatment failure was 5.8 months (mos) (range, 0.2–19.4). There were 2 on-study deaths (sepsis and PD). Grade 3–4 treatment-related toxicities reported in &gt;1 pt were thrombocytopenia (15%), asthenia (10%), neutropenia or neuropathy (8% each), peripheral neuritis (6%), and nausea (4%). Twenty patients discontinued study treatment due to toxicity (22%), pt request (6%), disease progression, ineligibility, and intercurrent illness/protocol deviation (4% each). 26 pts (52%) completed the study; 4 pts are still on study (8%). Sixteen pts started new treatment; median time from start of study treatment to the start of new treatment was 5.2 mos (range, 1.5–17.6 mos). The study was closed earlier than the planned due to the widespread availability of B, and the inability to find B-naïve patients. Bortezomib given after high-dose melphalan therapy and autologous PBSCT was well-tolerated with manageable adverse events. Updated cytogenetic analysis will be available for presentation.

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