Original Article
REVISTA PAULISTA DE MEDICIN APrognosis re late d to staging syste ms for
chronic lymphocytic le uke mia
Universidade Federal de São Paulo/Escola Paulista de Medicina,
São Paulo and Universidade de Alfenas, Alfenas, Brazil.
a b s t r a c t
CO N TEX T: C hro nic lymp ho c ytic le uke mia (C LL) is a c lo na l lympho pro liferative diso rder, characteriz ed by B lympho cytic pro lif-eratio n. CLL is the mo st frequent adult leukemia in W estern co un-tries, acco unting fo r 2 5 to 3 0 % o f all white leukemic patients.
OBJECTIVE: To evaluate clinical and stag ing characteristics in pro g -no sis o f chro nic lympho cytic leukemia.
DESIGN : Evaluatio n o f clinical-stag ing data.
SETTIN G: Universidade Federal de São Paulo - Esco la Paulista de Medicina / Universidade de Alfenas.
SAM PLE: 7 3 patients diag no sed fro m 1 9 7 7 to 1 9 9 4 .
M AIN M EASUREM EN TS: Sex, ethnic o rig in, ag e, lymphadeno pa-thy, spleno meg aly, hepato meg aly, three o r mo re areas o f lympho id enlarg ement, hemo g lo bin (g / dl), lympho cytes/ mm3, Platelets/ mm3
RESULTS: Mean survival o f patients was 7 6 mo nths, median ag e was 6 5 years, rang ing fro m 3 3 to 8 7 . Fo rty-fo ur patients (6 0 .3 %) were male and 2 9 (3 9 .7 %) female.
CON CLUSION : The Binet system determined a better pro g no sis than Rai.
KEY W ORDS: Chro nic Lympho cytic Leukemia. Pro g no sis. Clinical. Stag ing .
• Jo sé Ro berto de Faria •Jo sé Salvado r Ro drig ues de O liveira • Ro sa Malena Delbo ne de Faria • Maria Reg ina Reg is Silva • Samuel G o ihman • Mio ho ko Yamamo to • Jo sé Kerbauy
INTRODUCTION
Chro nic lympho cytic leukemia (CLL) is a clo nal lympho pro liferative diso rder, characterized by B lym-pho cytic pro liferatio n.1 CLL is the mo st frequent adult
leukemia in Western co untries, acco unting fo r 25 to 30% o f all white leukemic patients.2 The mean age fo r
the disease is greater than 50 years and the male to female ratio is 2:1.3 The illness seems to o ccur in 0.8
new cases per 100,000 perso ns per year in Brazil.4
Mo st patients are asympto matic regarding anemia, lymph no des, spleen and/o r liver enlargement, as well as fo r hemo rrhages and infective co mplicatio ns demanding medical attentio n.1,5 Rai et al.6 suggested that a persistent
peripheral blo o d lympho cytic co unt greater than 15000 per mm3
and lympho cytic marro w cellularity greater than 40% are essential findings fo r making its diagno sis.
Many studies have been tried, since early in the 20th century, to determine pro gno stic facto rs and stag-ing systems fo r predictstag-ing survival. These studies were co nso lidated into the criteria devised b y Rai et al. (1975)6 and Binet et al. (1981).7
Rai’s pro po sals co nsisted o f 5 established steps: stage 0 - o nly lympho cyto sis (in blo o d as well as in marro w); stage I - lympho cyto sis asso ciated with en-hanced lymph no des; stage II - lympho cyto sis plus liver and/o r spleen enlargement, with o r witho ut lymph no de invo lvement; stage III - lympho cyto sis in the presence o f anemia, defined by hemo glo bin levels belo w 11 g/dl; stage IV - lympho cyto sis plus thro mbo cyto penia, evalu-ated by a platelet co unt o f less than 100,000 per mm3
.6
Binet et al.7 summarized the Rai system and
pres-ence o f o ne o r two lympho id enlargements; B - three o r mo re areas and C - presence o f anemia co nfirmed by hemo glo bin less than 10 g/dl o r thro mbo cyto penia, with a platelet co unt o f less than 100,000 per mm3
.
The Internatio nal Wo rksho p o n CLL (1981) rec-o mmended the assrec-o ciatirec-o n rec-o f Binet and Rai in rec-o rder trec-o analyze clinical and evo lutio n data. The fo llo wing stages were suggested: stage A(0), A(I) and A(II) as lo w risk; B(I), B(II) as intermediate and C(III) and C(IV) as high risk.8 Ho wever, in actual practice, this system was no t
co mpletely acceptable wo rldwide, and clinicians have co ntinued to use either the Binet o r Rai metho ds.9 The
Natio nal Cancer Institute (1996) pro po sed a mo dified Rai system as fo llo ws: lo w risk (Rai stage 0); intermedi-ate risk (Rai stage I plus stage II) and high risk (Rai stage III plus IV).9 At the mo ment many o ther pro gno stic
fac-to rs are being studied, particularly abno rmal expres-sio n o f o nco genes (Bcl-2, Bcl-XL, Bcl-W, Bax, Bak, Mcl-1, Bag, p-53, and o thers).10
Our intentio n here was to evaluate clinical and staging features in Brazilian CLL patients so as to un-derstand their pro gno stic meaning better, by co mpar-ing the Binet, Rai, and mo dified Rai stagmpar-ing systems.
METHODS
One hundred and two CLL patients were admit-ted into São Paulo Ho spital and Alzira Velano Ho spi-tal between 1977 and 1994. The data fo r 26 o f them were no t co nsistent with what was o n their medical
registers, which might have allo wed us to determine either their survival o r clinical staging, and 3 o ther patients had misinterpreted diagno ses. The 73 remain-ing patients were included fo r final evaluatio n. All o f these fulfilled Binet, Rai and mo dified Rai staging re-quirements.
All patients were sub mitted to co nventio nal chemo therapy schedules with co mbinatio ns o f o ral chlo rambucil and predniso ne fo r early stage disease o r cyclo pho sphamide , vincristine , pre dniso ne and adriamycin fo r advanced disease.
Diagno sis was based o n histo ry, physical exami-natio n, presence o f mo re than 5.0 x 103 lympho cytes
per mm3
in peripheral blo o d, and at least 30% o f lym-pho cytic marro w invo lvement in marro w aspiratio n analysis.1 The staging was o btained acco rding to the
Binet,7 Rai6 and mo dified Rai systems.9 Survival curves
were o btained by limited extrapo latio n o f the Kaplan & Meier metho d.11
The curves o btained were co mpared using the Wilco xo n and Co x-Mantel tests.12
.
Multivari-ate analyses were perfo rmed using multiple Co x re-gressio ns.13,14 “P” was co nsidered to be significant when
less than 0.05, fo r all tests. The statistical pro grams utilize d we re : KMSURV - Univariate Survival Data Analysis, May 89, Ludwig Institute fo r Cancer Research, São Paulo Branch - Epidemio lo gy and Bio statistics Unit; BMDP - Bio m e dical Data Package - Survival Analysis with Co variates - Co x Mo dels, May 84, Health Science Co mputing Facility, University o f Califo rnia (UCLA), Lo s Angeles.14
Table 1. Re sults of the univariate analysis
Va ria ble Ca tegory N umber (%) M ea n Surviva l (months) P
Sex Males 4 4 (6 0 .3 %) 6 1 .1 3 0 .0 9
Females 2 9 (3 9 .7 %) 8 7 .7 6
Ethnic o rig in W hites 6 0 (8 2 .2 %) 7 4 .1 2 0 .7 2
N o n-whites 1 3 (1 7 .8 %) 6 5 .1 5
Ag e > 6 5 3 7 (5 0 .7 %) 7 8 .5 0 0 .5 5
< 6 5 3 6 (4 9 .3 %) 6 6 .9 1
Lymphadeno pathy Present 4 0 (5 4 .8 %) 5 3 .6 7 0 .2 7
Absent 3 3 (4 5 .2 %) 8 2 .8 4
Spleno meg aly Present 2 9 (3 9 .7 %) 5 8 .8 8 0 .0 7
Absent 4 4 (6 0 .3 %) 1 2 4 .1 2
Hepato meg aly Present 2 4 (3 2 .9 %) 6 3 .3 3 0 .2 3
Absent 4 9 (6 7 .1 %) 1 2 0 .1 6
Three o r mo re areas o f Present 1 7 (2 3 .3 %) 4 2 .4 7 0 .0 1
lympho id enlarg ement Absent 5 6 (7 6 .7 %) 9 0 .5 4
Hemo g lo bin (g / dl) > 1 0 4 7 (6 4 .4 %) 9 4 .0 7 0 .0 0 1
< 1 0 2 6 (3 5 .6 %) 3 3 .7 4
Hemo g lo bin (g / dl) > 1 1 3 9 (5 3 .4 %) 9 4 .7 2 0 .0 0 4
< 1 1 3 4 (4 6 .6 %) 3 6 .9 4
Hemo g lo bin (g / dl) < 1 0 3 0 (4 1 .1 %) 3 6 .0 3 0 .0 2
< 1 2 and >1 0 2 0 (2 7 .4 %) 6 7 .8 2
> 1 2 2 3 (3 1 .5 %) 9 8 .4 9
Lympho cytes / mm3 > 3 6 ,0 0 0 3 7 (5 0 .7 %) 5 4 .2 3 0 .0 3
< 3 6 ,0 0 0 3 6 (4 9 .3 %) 8 9 .4 6
Platelets / mm3 > 1 0 0 ,0 0 0 5 8 (7 9 .5 %) 8 8 .5 5 0 .0 3
RESULTS
There were 56 (76.7%) live patients at the end o f o ur o bservatio n. Mean survival was 76.1 mo nths, rang-ing fro m 1 to 140. Fo rty-fo ur (60.3%) were male (M) and 29 (39.7%) female (F), with M/F ratio o f 1.52. Mean age was 63.9 years, ranging fro m 33 to 87. Mean sur-vival after the age o f 65 years was 78.5 mo nths versus 66.9 befo re this (P = 0.55). Females had lo nger sur-vival than males, but no t reaching statistical signifi-cance (P = 0.09). Table 1 sho ws the univariate analysis results. To better co mpare patients in Binet stages A and B, all tho se with anemia and thro mbo cyto penia (stage C) were excluded fo r separated analysis (Table 2). Mean survival acco rding to the Rai, mo dified Rai and Binet staging systems is summarized in Table 3.
Univariate and multivariate analysis
Seven variables were co mpared with pro gno sis (survival): 1) hemo glo bin levels with cuto ffs o f 12, 11 and 10 g/dl, with P = 0.02, 0.004 and 0.001, respec-tively (Figure 1); 2) Binet staging system (P = 0.003; Figure 2); 3) Rai staging system (P = 0.02); 4) Mo dified Rai staging system (P = 0.007); 5) Number o f lympho id enhancement areas (P = 0.01); 6) Platelet co unt, with a cuto ff o f 100,000 per mm3 (P = 0.03); and 7) Number
o f lympho cytes in peripheral blo o d, greater than 36,000 per mm3 (P = 0.03). Ho wever, multivariate analysis o nly
sho wed a significant independent effect o n survival fo r the Binet system.
DISCUSSION
Since the Mino t & Isaacs study,15
many o ther studies have been carried o ut with the purpo se o f bet-ter establishing the pro gno sis o f patients with CLL. Rai and Binet repo rted useful co ncepts but, so far, no paper has explained the hetero geneity in the pro gno -sis o f CLL.16
We began o ur study with the analysis o f patients’ sex. There is agreement in the literature that the inci-dence is higher in men than in wo men, with the male/ female ratio being abo ut 2:1.17 Our cases sho wed a
1.52/1.00 ratio , which co nfirms the same tendency. Repo rts o n the impo rtance o f patients’ sex o n the pro g-no sis are also hetero geneo us in their results. Many autho rs have repo rted a better pro gno sis in wo men when co mpared to men,18-22 while o thers have no t
fo und a significant difference between the sexes.23-26
Our findings co incide with tho se o f the latter gro up. Altho ugh we fo und higher mean survival amo ng fe-males, the difference was no t significant.
Patients’ ages at the time o f diagno sis mo st fre-quently range between the 6th and 7th decades o f life.27
The average age in o ur cases was 63.9 years, with a median o f 65 years, similar to the literature. The rela-tio nship o f age to pro gno sis is no t ho mo geneo us in the literature. Mino t & Isaacs15 and Pao lini et al.20 co
r-related lo w age with a bad pro gno sis, but Bo ggs et al.,23 Hansen18 and Lee et al.21 repo rted the o ppo site.
Altho ugh we fo und a higher mean survival in patients aged o ver 65 years, age differences were no t statisti-cally significant in o ur study (P = 0.55).
The incidence o f CLL in Africa seems to be lo wer when we co mpare it with the incidence in white men. Acco rding to Linet & Cartwright,27
this fact is due no t to lo w incidence amo ng black peo ple, but to the lack o f diagno sis. We co nsider that it is no t advisable to analyze pro gno sis in relatio n to race in Brazil, in view o f the great interracial mixing in this co untry. We fo und a higher incidence in white patients (82.2%). Ho wever, this do es no t permit us to co nclude that there is a genuinely lo w incidence in black peo ple. The skin co lo r was no t significant in survival (P = 0.72).
No difference was fo und in o ur study regarding the mean o f patients’ survival when we analyzed the p re s e n c e o f ad e n o m e g aly, s p le n o m e g aly an d hepato megaly (Table 1). Nevertheless, when we ana-lyzed the presence o f mo re than 3 areas o f infiltratio n, there was a significant relatio n with survival (P = 0.01). As there was a significant difference in the sur-vival o f patients in Binet’s stages A and B, we perfo rmed the analyses o f the same clinical variables, excluding the patients with anemia and/o r thro mbo cyto penia, to avo id the effect o f these latter variables o n the pro gno -sis. Thus, in patients witho ut anemia and/o r thro mb-o cytmb-o penia, we mb-o bserved that the presence mb-o f bmb-o th adeno megaly (P = 0.04) and spleno megaly (P = 0.02) caused a lo wer survival. Hepato megaly sho wed lesser impo rtance in the determinatio n o f survival (P = 0.06) and the number o f affected areas was the mo st statisti-cally significant parameter (P = 0.01). These findings permit us to co nclude that pro gno sis really changes with the extent o f the disease (Table 2).
Table 2. Me an survival (months) of patie nts conside ring clinical variable s e xce pt ane mia and
thrombocytope nia
Va ria ble Present Absent P
Lymphadeno pathy 5 6 .4 9 1 1 5 .2 5 0 .0 4
Spleno meg aly 7 3 .9 2 1 4 0 .0 0 0 .0 2
Hepato meg aly 7 9 .2 6 1 4 0 .0 0 0 .0 6
Amo ng the clinical variables, hemo glo bin exhib-ited the mo st significant relatio nship with survival. Ac-co rding to vario us autho rs,6,7,15,18,23,24,28 hemo glo bin is o ne
o f the mo st impo rtant variables in the survival o f pa-tients with CLL, and o ur results agree with tho se in the
literature. We first analyzed hemo glo bin at two cuto ff levels (10 g/dl and 11 g/dl). As we fo und a significant relatio nship with survival at bo th levels (P = 0.001 and 0.004, respectively), we subdivided the hemo glo bin lev-els into three gro ups (Hb = 10 g/dl, 10 g/dl < Hb < 12 g/ dl and Hb = 12 g/dl). Even with the subdivisio n into three gro ups, the hemo glo bin levels kept a significant relatio nship with survival (P = 0.006), sho wing a mean survival time o f 36.20 mo nths, 68.45 mo nths, and 98.49 mo nths, respectively. We have thus demo nstrated that, as the levels o f hemo glo bin decrease, the patients’ mean survival time also decreases. The hemo glo bin thresho ld fo r the determinatio n o f anemia was arbi-trarily cho sen as 10 g/dl in Binet’s staging and 11 g/dl in Rai’s staging. Hence, we think that patients with C(III) staging sho uld no t be co nsidered in relatio n o nly to the presence o f anemia, but sho uld also be evaluated fo r hemo glo bin level as a pro gno sis determinant, as pro gressively lo wer hemo glo bin values lead to pro gres-sively wo rse pro gno ses (Table 1, Figure 1).
A platelet co unt lo wer than 100,000 per mm3 (P
= 0.02) represented a significant pro gno sis, as well as a lympho cyte co unt o f greater than 36,000 per mm3 (P
= 0.03). With regard to platelet co unt, o ur results agree with tho se o f Rai et al.,6 but disagree with o thers.21,31-33
Fo r the latter, anemia sho uld be a mo re relevant fac-to r than thro mbo cyfac-to penia. The pro gno stic signifi-c an signifi-c e o f th e lym p h o signifi-c yte signifi-c o u n t is signifi-c o n tro ve r-sial.15,18,19.24,25,29-31
In o ur o bservatio ns, with cuto ffs at 50,000/mm3, 100,000/mm3, and 150,000/mm3, we fo und
no significant relatio nship with survival, pro bably be-cause patients with mo re than 36,000 per mm3 may
present a wo rse pro gno sis, as was also o bserved by Baccarani et al.30
We fo und that the three mo st impo rtant clinical variables fo r pro gno sis o f CLL patients are hemo -glo bin with a cuto ff at 10 g/dl (P = 0.001); number o f lympho id infiltratio n areas (P = 0.01), sho wing o ur agreement with the parameters fo r determinatio n o f gro ups A, B and C o f the Binet staging system;7 and
peripheral lympho cyto sis (P = 0.03).
After evaluating o ur patients in acco rdance with Rai’s staging, o ur findings agree with tho se in the lit-erature. There was a significant difference in survival in o ur gro ups, but it did no t decrease fro m stage 0 to stage IV. Survival was sho rter in stage I than in stage II, but it may have o ccurred due to the sample size (6 patients) and a briefer fo llo w-up. Mo reo ver, all o f them were alive at the end o f this study. Survival in stage IV was no t sho rter than in stage III, which suggested that the platelet co unt may no t have significant impo rtance in the pro gno sis o f CLL.
Table 3 - Me an Survival (months) according to the Rai, Bine t and modifie d Rai staging syste ms
Sta ge N umber (%) Surviva l P
Rai
O * 1 1 (1 5 .0 ) 1 4 0 .0 0 0 .0 2
I* 6 (0 8 .2 ) 2 7 .0 0 II 2 6 (3 5 .6 ) 7 9 .8 2 III 1 4 (1 9 .1 ) 1 3 .1 7 IV 1 6 (2 1 .9 ) 3 6 .4 6
Binet
A 2 9 (4 0 .7 %) 1 1 5 .2 5 0 .0 0 3
B 1 4 (1 9 .2 %) 5 2 .0 5
C 3 0 (4 1 .1 %) 3 1 .0 1
Mo dified Rai
Lo w risk* 1 1 (1 5 .0 %) 1 4 0 .0 0 0 .0 0 7 Intermediate risk 3 2 (4 3 .9 %) 8 3 .3 4
Hig h risk 3 0 (4 1 .1 %) 3 2 .0 1
* All patients were alive at the time o f cuto ff.
Figure 1 - Survival of CLL patients according to hemoglobin (Hb) level. P
Figure 2 - Survival of CLL patients according to Binet staging system.7
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02. Bartal A, Bentwich Z, Manny N, et al. Clinical aspects o f chro nic lympho cytic leukemia in Israel. Acta Haemato l 1978;60:161-71.
03. Jo hnso n LE. Chro nic lympho cytic leukemia. Practical Therapeutics 1988;38(suppl 6):167-76.
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07. Binet JL, Auquier A, Diguiero G, et al. A new pro gno stic classificatio n o f chro nic lympho cytic leukemia derived fro m a multivariate survival analysis. Cancer 1981;48:198-206.
08. Binet JL, Cato vsky D, Chandra B, et al. Pro po sals fo r a revised staging system. Br J Haemato l 1981;48:365-7.
09. Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute - Sponsored working group guidelines for chronic lymphocytic leukemia: revised guidelines fo r diagno sis and treatment. Blo o d 1996;87(12):4990-7.
10. Kitada S, Andersen J, Akar S, et al. Expressio n o f apo pto sis-regulating pro teins in chro nic lympho cytic leukemia: co rrelatio ns with in vitro and in vivo chemo respo nses. Blo o d 1998,91(9):3379-89.
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19. Zippin C, Cutler SJ, Reeves WJ, et al. Survival in chro nic lympho cytic leukemia. Blo o d 1973;42:367-76.
20. Pao lino W, Infelise V, Levis A, et al. Adeno spleno megaly and pro gno sis in unco mplicated and co mplicated chro nic lympho cytic leukemia: a study o f 362 cases. Cancer 1984;54:339-46.
21. Lee JS, Dixo n DO, Kantarjian HM, et al. Pro gno sis o f chro nic lympho cytic leukemia: a multivariate regressio n analysis o f 325 untreated patients. Blo o d 1987;69:929-36.
22. Juliusso n G, Oscier DG, Fitchett M, et al. Pro gno stic subgro ups in B-cell c hro nic lym p ho c ytic le uke m ia d e fine d b y sp e c ific c hro m o so m al abno rmalities. N Engl J Med 1990;323(suppl 11):720-41.
23. Bo ggs DR, So fferman SA, Wintro be MM, et al. Facto rs influencing the duratio n o f survival o f patients with chro nic lympho cytic leukemia. Am J Med 1966;40:243-54.
24. Co ue r P, Ge ntilho m m e O, Mo re l P, e t al. Vale ur p ro no stiq ue d e l’hémo gramme et du myélo gramme initial dans la leucémie lympho ide chro niq ue: étude statistiq ue de 310 o b servatio ns par la métho de actuarielle. No uv Rev Fr Hemato l 1970;10:566-75.
25. Geisler C, Ralflaer E, Hansen MM, et al. The bo ne marro w histo lo gical patte rn has inde pe nde nt pro gno stic value in e arly stage chro nic lympho cytic leukaemia. Br J Haemato l 1986;62:47-54.
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29. Ro zman C, Hernandez-Nieto L., Mo ntserrat E, et al. Pro gno stic significance o f bo ne marro w patterns in chro nic lympho cytic leukaemia. Br J Haemato l 1981;47:529-37.
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Altho ugh classic, the Rai system subdivides the disease into 5 stages, making the treatment appro ach mo re difficult due to the great numb er o f sub gro ups. Mo reo ver, Rai co nsiders that liver and spleen infil-tratio n o ccurs later than lymph no de enlargement. So me autho rs18,23,28 have no t infreq uently o b served
c ase s o f m arke d sp le no m e galy in the ab se nc e o f adeno megaly. The mo dified Rai system is similar to the Binet system and was significant in the univariate analysis (P = 0.007), b ut despite the small numb er o f gro ups the multivariate analysis sho wed that the Bi-net metho d expresses a b etter pro gno sis o f CLL. We have also demo nstrated that b o th the hemo glo b in level and the numb er o f lympho id areas invo lved, as
seen b y Binet et al.,7 co rrelate with survival in the
univariate analysis. Ho wever, o nly the Binet system remained significant in the multivariate analysis, b e-ing a simpler and mo re accurate metho d fo r evaluat-ing the pro gno sis o f CLL.
CONCLUSIONS
r e s u m o
CON TEXTO: Diversas variáveis clínicas se relacio nam ao pro g nó stico na leucemia linfo cítica crô nica; no entanto , o estadiamento de Binet determina melho r o pro g nó stico do que o estadiamento de Rai e Rai mo dificado .
O BJETIV O : Ava lia r c a ra c te rístic a s c línic a s e la b o ra to ria is no pro g nó stico da leucemia linfo cítica crô nica.
TIPO DE ESTUDO: Estudo s de co rrelação .
LO CAL: Universidade Federal de São Paulo - Esco la Paulista de Medicina / Universidade de Alfenas.
PARTICIPAN TES: 7 3 patients diag no sticado s entre 1 9 7 7 e 1 9 9 4 .
VA RI Á V EI S ESTU D A D A S: Se x o , o rig e m é tnic a , id a d e , linfadeno meg alia, espleno meg alia, hepato meg alia, três o u mais áreas co m aumento linfó ide, hemo g lo bina, linfo cito s, plaquetas.
RESULTADOS: A so brevida média do s pacientes fo i 7 6 meses, idade média de 6 5 ano s, variando de 3 3 a 8 7 ano s. Q uarenta e quatro pacientes (6 0 ,3 %) eram do sexo masculino e 2 9 (3 9 ,7 %) do sexo feminino .A análise univariada mo stro u que o nível de hemo g lo bina (P = 0 ,0 0 1 ), número de plaquetas (P = 0 ,0 3 ), linfo cito se periférica (P = 0 ,0 3 ), número de áreas linfó ides aco metidas (P = 0 ,0 1 ), assim co mo o s estadiamento s de Rai (P = 0 ,0 2 ), Rai mo dificado (0 ,0 0 7 ) e Binet (P = 0 ,0 0 3 ) relacio naram-se sig nificantemente co m a so brevida. A análise multivariada, pela reg ressão de Co x, demo nstro u que o siste ma d e Bine t d e te rmina me lho r o p ro g nó stic o d o q ue o s estadiamento s de Rai e Rai mo dificado .
CON CLUSÃO: O estadiamento de Binet é melho r que o estadiamento de Rai e Rai mo dificado na determinação do pro g nó stico .
PALAV RAS-CHAV E: Le uc e mia linfo c ític a c rô nic a . Pro g nó stic o . Clínica. Estadiamento .
José Robe rto de Faria, MD. Divisio n o f Hemato lo gy, Universidade de Alfenas (UNIFENAS), Minas Gerais, Brazil.
José Salvador Rodrigue s de Olive ira, MD, PhD. Divisio n o f Hemato lo gy, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.
Rosa Male na De lbone de Faria, MD. Divisio n o f Hemato lo gy, Universidade de Alfenas (UNIFENAS), Minas Gerais, Brazil.
Maria Re gina Re gis Silva, MD, PhD. Divisio n o f Patho lo gy, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil. Samue l Goihman, MD. Divisio n o f Epidemio lo gy, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.
Miohoko Yamamoto, MD, PhD. Divisio n o f Hemato lo gy, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.
José Ke rbauy, MD, PhD, FACP. Divisio n o f Hemato lo gy, Universidade Federal de São Paulo / Esco la Paulista de Medicina, São Paulo , Brazil.
Source s of funding: No t declared Conflict of inte re st: No t declared Last re ce ive d: 3 January 2000 Acce pte d: 27 January 2000
Addre ss for corre sponde nce : Jo sé Ro berto de Faria Universidade de Alfenas Rua Geraldo de Freitas Co sta, 120 Alfenas/MG - Brasil - CEP 37130-000 e-mail: faria@ artefinal.co m.br
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