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Blood, Vol. 93 No. 1 (January 1), 1999:
pp. 51-54
Age Is Not a Prognostic Variable With Autotransplants for Multiple
Myeloma
By
D.S. Siegel,
K.R. Desikan,
J. Mehta,
S. Singhal,
A. Fassas,
N. Munshi,
E. Anaissie,
S. Naucke,
D. Ayers,
D. Spoon,
D. Vesole,
G. Tricot, and
B. Barlogie
From the Myeloma and Transplantation Research Center, University of
Arkansas for Medical Sciences and Arkansas Cancer Research Center,
Little Rock.
 |
ABSTRACT |
Multiple myeloma (MM) typically afflicts elderly patients with a
median age of 65 years. However, while recently shown to provide
superior outcome to standard treatment, high-dose therapy (HDT) has
usually been limited to patients up to 65 years. Among 550 patients
with MM and a minimum follow-up of 18 months, 49 aged  65 years were
identified (median age, 67; range, 65 to 76 years). Their outcome was
compared with 49 younger pair mates (median, 52; range, 37 to 64 years)
selected among the remaining 501 younger patients (<65 years) matched
for five previously recognized critical prognostic factors
(cytogenetics,  2-microglobulin, C-reactive protein,
albumin, creatinine). Nearly one half had been treated for more than 1 year with standard therapy and about one third had refractory MM. All
patients received high-dose melphalan-based therapy; 76% of the
younger and 65% of the older group completed a second transplant
(P = .3). Sufficient peripheral blood stem cells to support
two HDT cycles (CD34 > 5 × 106/kg) were available
in 83% of younger and 73% of older patients (P = .2).
After HDT, hematopoietic recovery to critical levels of granulocytes
(>500/µL) and of platelets (>50,000/µL) proceeded at comparable
rates among younger and older subjects with both first and second HDT.
The frequency of extramedullary toxicities was comparable.
Treatment-related mortality with the first HDT cycle was 2% in younger
and 8% among older subjects, whereas no mortality was encountered with
the second transplant procedure. Comparing younger/older subjects,
median durations of event-free and overall survival were 2.8/1.5 years
(P = .2) and 4.8/3.3 years (P = .4).
Multivariate analysis showed pretransplant cytogenetics and
2-microglobulin levels as critical prognostic features
for both event-free and overall survival, whereas age was insignificant for both endpoints (P = .2/.8). Thus, age is not a
biologically adverse parameter for patients with MM receiving high-dose
melphalan-based therapy with peripheral blood stem cell support and,
hence, should not constitute an exclusion criterion for participation
in what appears to be superior therapy for symptomatic MM.
© 1999 by The American Society of Hematology.
| |
INTRODUCTION |
MULTIPLE MYELOMA (MM) afflicts
approximately 13,000 Americans annually. Symptom manifestations relate
to anemia, osteopenia and lytic bone disease, hypercalcemia, renal
failure, and immunodifficiency.1,2 Over one half of the
patients are older than 65 years at diagnosis. After lack of progress
with standard-dose therapy over three decades,2 hematopoietic stem cell supported high-dose therapy (HDT) has become
the treatment of choice for symptomatic patients, especially younger
individuals who are thought to be able to withstand the potentially
greater toxicity incurred with myeloablative regimens.3-5 Fortunately, treatment-related mortality has decreased to 5% or less,
mainly as a result of rapid hematopoietic engraftment with the use of
peripheral blood stem cells (PBSC) collected early in the disease
course and mobilized with hematopoeitic growth factors alone or in
conjunction with chemotherapy.6
Since the introduction of autotransplants for MM,7,8 our
patients were eligible for HDT up to age 70. In recent years, we
essentially discontinued an upper age limit when disease severity was
judged to outweigh the anticipated toxicities from HDT. In extensive
analyses of both newly diagnosed and previously treated patients, age
did not factor in as an adverse feature for event-free survival (EFS)
and overall survival (OS).9 Instead, prognosis was
dominantly impacted by cytogenetics, 2-microglobulin
(B2M), and C-reactive protein (CRP) as well as duration of prior
therapy.10,11
Prompted by health insurance considerations for patients 65 years and
older, we examined patients' outcome after autotransplant-supported HDT in relationship to age. This report compares our experience with
HDT in 49 patients 65 years and 49 younger patients, after matching
for prognostically relevant pretreatment features.
| |
PATIENTS AND METHODS |
Between December 1989 and August 1997, 900 patients were enrolled in
tandem autologous transplant trials using melphalan 200 mg/m2 (MEL200) for the first cycle.9 A second
HDT cycle was usually administered within 3 to 6 months consisting of
MEL200 in case partial response (PR) was sustained. Patients with less
than PR status were offered combination therapy (MEL140 + total body
irradiation [TBI] 850 to 1125 cGy) or MEL200 and added
high-dose cyclophosphamide (HDCTX; usually 6 g/m2); the
latter regimen was used when patients were deemed not to be candidates
for a TBI-containing regimen because of prior local radiation. All PBSC
were collected before both autotransplants, either with HDCTX plus
granulocyte colony-stimulating factor (G-CSF) or granulocyte macrophage
CSF (GM-CSF) or with G-CSF alone as reported
previously.12,13
Forty-nine patients aged 65 years were identified who had a minimum
posttransplant follow-up of 18 months. During this time interval, 501 younger patients (<65 years) were also treated. Using a standardized
Euclidian distance measure,14 49 pair mates were identified
whose prognostically relevant disease, host, and treatment features
were comparable (Table 1). Pair mates were established using the following pretransplant prognostic factors: B2M,
albumin, creatinine, CRP, and the presence or absence of unfavorable
chromosomal abnormalities (11q breakpoints, monosomy 13 or deletion
13q, and any translocation).10,11
All patients had to sign an informed consent indicating the potential
benefit and toxicities associated with the tandem autotransplant programs. Protocols and consent forms had been reviewed and approved by
the institutional review board and, where appropriate, by the National
Cancer Institute and the Food and Drug Administration. Clinical
endpoints considered treatment-related mortality (TRM) within 60 days
of HDT, separately for first and second autotransplant. Additionally,
TRM was computed 6 and 12 months after the first HDT cycle. Complete
response (CR) was defined as the absence, on immunofixation analysis of
serum and urine, of monoclonal protein in the presence of normal
morphologic examination of bone marrow aspirate and biopsy with less
than 1% of tumor cells identified on the basis of DNA-cytoplasmic
immunoglobulin flow cytometric analysis.15 CR had to be
documented on at least two occasions at a minimum time interval of 3 months. EFS and OS were computed from the first HDT cycle. CR duration
was measured from the first onset of CR to disease relapse or death. In
addition, hematopoietic recovery was determined using threshold levels
for granulocytes of at least 500/µL and of platelets of at least
50,000/µL, both with first and second transplant. Grade III and IV
extramedullary toxicities were also determined.
Statistical methods used chi-squared tests for comparison of patient
characteristics, the Kaplan-Meier product limit method for estimation
of survival,16 and the log-rank test for comparison for CR
duration, EFS, and OS.17 Multivariate analysis was used to
determine the prognostically independent variables associated with
various clinical endpoints.18
| |
RESULTS |
The median age in the younger group ranged from 37 to 64 years (median,
52 years) and from 65 to 76 years (median, 67 years; 70 years, 7 patients; 71 years, 1; 72 years, 1; 76 years, 1 patient) among the
older patients (P = .0001). Patient characteristics were well
matched for the main risk factors previously identified to affect EFS
and OS after autotransplants10,11 (Table 1). Specifically,
the incidence of favorable cytogenetics (absence of aberrations of
chromosomes 11 and 13 as well as any translocation) was similar in
young patients and in the two older cohorts. Fifty-five percent to 70%
had 12 months of prior therapy. Fewer older patients presented with
low B2M  2.5 mg/L (P = .2). The proportion of patients with
high CD34 counts (>5 × 106/kg) was similar
(P = .4). A second transplant was applied in 76% of patients
<65 years, 69% in the 65 to 69 years group, and in 50% of those
70 years. As far as regimens were concerned, all patients received
MEL200 with the first autograft. The second transplant consisted of
MEL200 in 18 of 37 (49%) among those <65 years, 11 of 27 (41%) in
the middle age group, and in 4 of 5 (80%) in the old age group. MEL140 + TBI/MEL-HDCTX/other regimens were applied in 8/5/6 patients <65
years; and 12/2/2 of those aged 65 to 69 years and 1/0/0 in the
70-year group.
Granulocyte and platelet recoveries were superimposable in both age
groups, after first and second HDT cycle, indicating excellent PBSC
quantities and function (Fig 1). The
frequencies of extramedullary toxicities were similar in younger and
older patients during both transplant procedures (Table
2). TRM within 60 days of the first transplant was 2% in younger (intracranial hemorrhage, 1 patient) and
8% in older patients (death of unknown cause after complete hematopoietic recovery, 66 years; pneumonia, 69 years; intracranial hemorrhage subsequent to trauma, 70 years; sepsis caused by delayed engraftment after CD34-selected autograft, 70 years)
(P = .2). None of the second transplant recipients in either
age group experienced TRM.
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| Fig 1.
Similar recovery kinetics of granulocytes (>500/µL)
and of platelets (>50,000/µL) in young and old patients, with both
first and second transplant. The fraction of patients with CD34 >5 × 106/kg was comparable between age groups.
|
|
The incidence of CR was lower in older than in younger subjects (20 v 43%, P = .02). EFS and OS durations were
comparable (Fig 2) as were CR durations
(Fig 3). Multivariate analysis of pretransplant prognostic variables among all 98 patients identified favorable cytogenetics and low B2M as good risk features for both EFS
and OS; in addition, months of prior therapy was also important for
EFS. However, age was not a significant risk factor for either EFS or
OS once these variables were accounted for (Table
3).
View larger version (20K):
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[in a new window]
| Fig 2.
Similar durations of EFS and OS after
autotransplant-supported HDT in patients <65 and 65 years.
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| |
DISCUSSION |
This report confirms our previous experience that age per se does not
affect outcome after autotransplant for MM, whether examined as a
continuous or categorical variable. This finding may be due, in large
part, to the availability of adequate quantities of CD34+
cells in young and old patients, assuring comparable durations of
neutropenia and thrombocytopenia and, thus, minimizing the risk of
infection and other toxicities. A cumulative injury from a second HDT
cycle to either the bone marrow micro-environment or other critical
organs was not apparent in either age group. We confirm, in both young
and old patients, the importance of cytogenetics and B2M as key
variables for sustained disease control. On the basis of our results,
there is no biological justification for an age-discriminant policy for
MM therapy. In fact, the incidence and nature of complex chromosomal
aberrations did not differ among young and old, although different
pathogenetic mechanisms may still be revealed at the molecular level.
Palumbo et al recently reported on the safety and efficacy of
sequential HDT regimens with cyclophosphamide and melphalan ("CM"
regimen)19 as well as repeated sub-myeloablative doses of
MEL100 with PBSC support.20 In preparation for regular
inclusion of older subjects in HDT trials, we are currently evaluating
tandem autotransplants in patients 70 years and older, using MEL140
with the first HDT cycle and, depending on tolerance and antitumor effect, MEL140 or MEL200 with the second transplant. There are no
exclusions according to renal function (which we have shown not to
affect MEL clearance).21 We conclude that optimal therapy for MM with PBSC-supported high-dose melphalan therapy should not be
withheld from the majority of older patients presenting with MM who
deserve optimal control of their disease and, thereby, gaining
hopefully many years of high-quality life.
| |
ACKNOWLEDGMENT |
The authors greatly acknowledge the dedicated services of the nursing
staff, the confidence of many referring physicians who have entrusted
us with their patients' medical care, and to Caran Hammonds for
excellent secretarial assistance.
| |
FOOTNOTES |
Submitted June 3, 1998;
accepted September 1, 1998.
Supported in part by Grant No. CA55819 from the National Cancer
Institute, Bethesda, MD.
The publication costs of this
article were defrayed in part by
page charge payment. This article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
Address reprint requests to B. Barlogie, MD, PhD, University of
Arkansas for Medical Sciences, 4301 W Markham Slot 776, Little Rock, AR
72205.
| |
REFERENCES |
1.
Barlogie B:
Plasma cell myeloma, in
Beutler E,
Lichtman M,
Coller B,
Kipps T
(eds):
Hematology. William's Hematology (ed 5). New York, NY, McGraw-Hill, 1995, p 1109.
2.
Alexanian R, Dimopoulos M:
The treatment of multiple myeloma.
N Engl J Med
7:484, 1994
3.
Barlogie B, Jagannath S, Tricot G, Desikan KR, Fassas A, Siegel D:
Advances in the treatment of multiple myeloma, in
Schrier R
(ed):
Advances in Internal Medicine, vol 43. St Louis, MO, Mosby-Year Book, 1998, p 279.
4.
Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R:
A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma.
N Engl J Med
335:91, 1996[Abstract/Free Full Text]
5.
Barlogie B, Jagannath S, Vesole D, Tricot G, Naucke S, Cheson B, Mattox S, Bracy D, Salmon S, Jacobson J, Crowley J:
Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma.
Blood
89:789, 1997[Abstract/Free Full Text]
6.
Vesole DH, Barlogie B, Jagannath S, Crowley J, Cheson B, Tricot G:
High dose therapy for refractory multiple myeloma: Improved prognosis with better supportive care and double transplants.
Blood
84:950, 1994[Abstract/Free Full Text]
7.
Barlogie B, Hall R, Zander A, Dicke K, Alexanian R:
High-dose melphalan with autologous bone marrow transplantation for multiple myeloma.
Blood
67:1298, 1986[Abstract/Free Full Text]
8.
Barlogie B, Alexanian R, Dicke KA, Zagars G, Spitzer G, Jagannath S, Horowitz L:
High-dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma.
Blood
70:869, 1987[Abstract/Free Full Text]
9.
Vesole DH, Tricot G, Jagannath S, Desikan KR, Bracy D, Miller L, Cheson B, Crowley J, Barlogie B:
Autotransplants in multiple myeloma: What have we learned?
Blood
88:838, 1996[Abstract/Free Full Text]
10.
Tricot G, Sawyer J, Jagannath S, Bracy D, Mattox S, Vesole D, Naucke S, Barlogie B:
Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities.
Blood
86:4250, 1995[Abstract/Free Full Text]
11.
Tricot G, Sawyer J, Jagannath S, Desikan KR, Siegel D, Naucke S, Mattox S, Bracy D, Munshi N, Barlogie B:
The unique role of cytogenetics in the prognosis of patients with myeloma receiving high dose therapy and autotransplants.
J Clin Oncol
15:2659, 1997[Abstract/Free Full Text]
12.
Tricot G, Jagannath S, Vesole DH, Nelson J, Tindle S, Miller L, Cheson B, Crowley J, Barlogie B:
Peripheral blood stem cell transplants for multiple myeloma Identification of favorable variables for rapid engraftment in 225 patients.
Blood
85:588, 1995[Abstract/Free Full Text]
13.
Desikan KR, Barlogie B, Jagannath S, Vesole DH, Siegel D, Fassas A, Munshi N, Singhal S, Mehta J, Tindle S, Nelson J, Bracy D, Mattox S, Tricot G:
Comparable engraftment kinetics following peripheral blood stem cell infusion mobilized with G-CSF with or without cyclophosphamide in multiple myeloma.
J Clin Oncol
16:1547, 1998[Abstract/Free Full Text]
14.
Smith AH, Kark JD, Cassel JC, Spears GFS:
Analysis of prospective epidemiologic studies by minimum distance case-control matching.
Am J Epidemiol
105:567, 1997[Abstract/Free Full Text]
15.
Barlogie B, Alexanian R, Pershouse M, Smallwood L, Smith L:
Cytoplasmic immunoglobulin content in multiple myeloma.
J Clin Invest
76:765, 1985
16.
Kaplan EL, Meier P:
Nonparametric estimation from incomplete observations.
J Am Stat Assoc
53:457, 1958
17.
Mantel N:
Evaluation of survival data and two new rank order statistics arising in its consideration.
Cancer Chemother Rep
50:163, 1966[Medline]
[Order article via Infotrieve]
18.
Cox DR:
Regression models and life-tables (with discussion).
J R Stat Soc Series B
34:187, 1972
19.
Palumbo A, Pileri A, Triolo S, Omede P, Bruno B, Cirvegna G, Galliano M, Frieri R, Boccadoro M:
Multicyclic, dose-intensive chemotherapy supported by hemopoietic progenitors in refractory myeloma patients.
Bone Marrow Transplant
19:23, 1997[Medline]
[Order article via Infotrieve]
20.
Palumbo A, Pilerio A, Triolo S, Bringhen S, Rus C, Triolo R, Ravaglia R, Boccadoro M:
Intensified therapy with stem cell support (MEL100) for elderly myeloma patients.
Blood
90:231a, 1997 (abstr, suppl 1)
21.
Tricot G, Alberts DS, Johnson CS, Roe DJ, Dorr RT, Vesole DH, Jagannath S, Meyers R, Barlogie B:
Safety of autotransplants with high dose melphalan in renal failure: A pharmacokinetic and toxicity study.
Clin Cancer Res
6:947, 1996
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Abstract
Introduction