Original Article
REVISTA PAULISTA DE MEDICIN APrognostic factors in non-Hodgkin lymphomas
Department of Hematology and Transfusion Medicine,
Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, Brazil
INTRODUCTION
In Ho dgkin’s disease, each clinical o r patho lo gic stage can be related to the extent o f the area invo lved and predicts the next anato mical regio n at risk fo r tu-mo r disseminatio n. Thus, the Ann Arbo r staging crite-ria1,2 are useful in planning treatment and
determin-ing the evo lutio n o f the disease. Ho wever, the bio lo gi-cal b ehavio r o f no n-Ho dgkin lympho mas (NHL) is much mo re co mplex in relatio n to their presentatio n and natural histo ry. In this way, discrepancies between NHL fo und in the vario us subgro ups make it impo s-sible to analyze them all to gether, and in particular we canno t predict survival based o nly o n the anato mi-cal areas invo lved.
Age, general co nditio n at the time o f diagno sis, serum lactate dehydro genase (LDH) level, extrano dal invo lvement and tumo r burden assessment are the facto rs that have been sho wn to have pro gno stic value fo r survival in many studies.3-7 There are so me
varia-tio ns between the different autho rs. We studied all these parameters in o rder to understand better which o f these co uld predict survival amo ng a set o f patients o f lo w so cio eco no mic level treated in a public ho spi-tal in the city o f São Paulo .
METHODS
An initial analysis o f 142 patients with NHL was made, who se bio psies were reviewed and classified in acco rdance with the Working Formulation (WF)8
between February 1988 and March 1993 in o ur institutio n. Fro m this, 29 patients were excluded due ineligible data, a b s t r a c t
CON TEX T: In Ho dg kin’s disease, each clinical o r patho lo g ic stag e can be related to the extent o f the area invo lved and predicts the next anato mical reg io n at risk fo r tumo r disseminatio n.
OBJECTIVE: To determine the best pro g no stic facto rs that co uld pre-dict survival in no n-Ho dg kin lympho ma cases.
DESIGN : A retro spective study.
LOCATION : Department o f Hemato lo g y and Transfusio n Medicine, Universidade Federal de São Paulo - Esco la Paulista de Medicina.
PARTICIPAN TS: 1 4 2 patients with no nHo dg kin lympho ma diag -no sed between February 1 9 8 8 and March 1 9 9 3 .
M AIN M EASUREM EN TS: Histo lo g ical subset, Sex, Ag e, Race, B sympto ms, Perfo rmance status, Stag e, Extrano dal disease, Bulk dis-ease, Mediastinal disdis-ease, CN S invo lvement, BM infiltratio n, Level o f DHL, Immuno pheno type.
RESULTS: In the first study (1 1 3 patients), the fo llo wing variables had a wo rse influence o n survival: yello w race (P<0 .1 ); ECO G II, III e IV (P<0 .1 ) and extrano dal disease (P<0 .1 ) fo r hig h g rade lympho -mas; co nstitutio nal sympto ms (P<0 .1 ), ECO G II, III e IV (P<0 .1 ) and invo lvement o f CN S (P<0 .1 ) fo r intermediate g rade and the subtype lympho plasmo cyto id (P=0 .0 1 8 6 ) fo r lo w g rade lympho mas. In the seco nd survey (9 3 patients), when treatment was included, the vari-ables related to N HL survival were: CN S invo lvement (P<0 .1 ) fo r hig h g rade lympho mas, co nstitutio nal sympto ms (P<0 .1 ), ECO G II, III, IV (P=0 .0 1 8 5 ) and also CN S invo lvement (P<0 .1 ) fo r the inter-mediate g ro up. There were no variables related to the survival fo r lo w-g rade lympho mas.
CON CLUSION S: The intermediate g rade lympho mas were mo re co m-patible with data fo und in the literature, pro bably because o f the larg er number o f patients. In this specific case, the treatment did no t have an influence o n the survival.
KEY-W ORDS: N o n-Ho dg kin lympho ma. Pro g no stic Facto rs. Survival.
plete and differential blo o d cell co unt; bio chemistry test, particularly the LDH level; chest x-ray; chest, ab-do men and pelvis CT scans; and bilateral bo ne mar-ro w bio psies. So me special pmar-ro cedures such as lum-bar puncture, brain CT o r percutaneo us liver bio psy were perfo rmed o nly if there was clinical suspicio n o f lo cal invo lvement. Each patient was characterized us-ing the fo llo wus-ing remissio n criteria after treatment: co mplete remissio n (CR), defined as a co mplete ab-sence o f any clinical o r labo rato ry (bio chemical o r ra-dio lo gical) signs o f disease maintained fo r at least fo ur sequential weeks; partial remissio n (PR), defined as a reductio n in tumo r burden o f 50% o r mo re, measur-able in two dimensio ns at the same time; refracto ry disease (RD), defined as a reductio n in tumo r burden o f less than 50% co mpared with the o riginal size, o r a co mplete failure o f respo nse to treatment, o r evidence o f gro wing tum o r b urd e n d uring two se q ue ntial therapy cycles. The disease free-survival (DFS) was taken as the length o f time between CR and the last co nsultatio n o r the relapse. The o verall survival (OS) used the same criteria fo r all patient situatio ns.
The fo llo wing clinical variables were evaluated: age in years; sex; race; general co nditio n (perfo rmance status) in acco rdance with the Eastern Co o perative Onco lo gy Gro up (ECOG);8 extrano dal site invo lvement;
presence o f bulk disease defined as a tumo r burden mass larger than 10 cm in o ne diameter o r o ccupying mo re than o ne third o f the mediastinum; and CNS invo lvement. The LDH level was sco red at three lev-els:
≤
225 U/dl; > 225 and < 450 U/dl; and≥
450 U/dl. Bio psies fro m different disease sites, mo stly lympho id no des, were reviewed in the Patho lo gy Department and reclassified acco rding to the WF. When there were plenty o f samples, immuno histo lo gical studies were do ne o n the B (CD-20) and T (CD45RO) markers using the ABC metho d.9 The clinical stages were determinedin acco rdance with the Ann Arbo r classificatio n. Seven different, no n-rando mized chemo therapy regimens were used. These were cho sen based o n the initial WF histo lo gical classificatio n. The seco nd and third gen-e ratio n s c h gen-e m gen-e s s u c h as Mac o p - B,7 Pro m ac e
-CYTAbo m8 and the BFM-83 high-risk pro to co l9 were
use d fo r high grade gro ups. CHOP,10
BACOP10
and MVPP11 were used fo r intermediate gro ups. Fo r lo w
grade lympho ma, COP11 and MVPP11 were the mo st
o ften used pro to co ls.
Statistical Methods. Survival curves were plo tted acco rding to the metho d o f Kaplan and Meier.12
Sta-tistical significance amo ng curves was determined by the Co x-Mantel metho d, measuring variables with two catego ries o f results, and the generalized Wilco xo n test leaving the 113 patients that co nstituted o ur first study.
A seco nd analysis was carried o ut o n 93 patients who co mpleted their fo llo w-up and co uld be evaluated as regards their treatment.
The staging o f the disease were do ne befo re and after treatment. The tests perfo rmed included: co
m-Table 1- Characte ristics of patie nts with high grade lymphoma
1st a na lysis 2nd a na lysis
Variables nºpatients P-value nº patients P-value Histologica l subset
Immuno blastic 1 2 0 .4 2 0 9 0 .5 4 SN CC 0 2 0 1
Lympho blastic 0 3 0 3 Unclassified 0 4 0 3
Sex
Female 0 5 0 .0 6 1 1 0 .1 5 Male 1 6 0 5
Age (yea rs)
< 6 0 1 9 0 .9 2 1 4 0 .4 2 > 6 0 0 2 0 2
Ra ce
W hite 1 5 0 .0 4 1 1 0 .0 7 Black 0 4 0 4
Yello w 0 2 0 1
B symptoms
Present 1 3 0 .1 5 0 9 0 .6 2 Absent 0 8 0 7
Performa nce sta tus
0 0 3 <0 .0 1 0 2 0 .5 2
1 1 2 1 0
2 0 4 0 3
3 0 4 0 1
4 0 1 0 0
Sta ge
I 0 2 0 .0 9 0 2 0 .1 3
II 0 7 0 4
III 0 6 0 5
IV 0 6 0 5
Ex tra noda l disea se
Present 0 3 <0 .0 1 0 3 0 .0 6 Absent 1 8 1 3
Bulk disea se
Present 1 0 0 .6 3 0 8 0 .4 8 Absent 1 1 0 8
M edia stina l disea se
Present 0 6 0 .6 3 0 4 0 .8 7 Absent 1 5 1 2
CN S involvement
Present 0 1 0 .1 4 0 1 <0 .0 1 Absent 1 6 1 5
BM infiltra tion
Present 0 5 0 .3 0 0 4 0 .1 7 Absent 1 6 1 2
Level of DHL
≤ 2 2 5 U/ dl 0 4 0 .8 8 0 4 0 .1 4 >2 2 5 and <4 5 0 U/ dl 0 6 0 5
≥ 4 5 0 U/ dl 0 4 0 2
Immunophenotype
B 0 9 0 .5 0 0 6 0 .6 5
T 0 1 0 1
fo r tho se variables with mo re than two catego ries o f results.
RESULTS
Patients’ parameters in relatio n to the grade o f lympho ma are sho wn in Tables 1 to 3 and the distri-butio n o f the 93 treated patients amo ng the different
chemo therapy schemes is sho wn in Table 4.
The remissio n rates fo r high-grade lympho mas were: 62% CR, 25% PR and 12% RD; fo r the intermedi-ate gro up: 50% CR, 27% PR and 23% RD; and fo r the lo w grade gro up: 44% CR, 32% PR and 24% RD. MACOP-B and CHOP were the treatments analyzed fo r high grade lympho ma and their CR were 66% and 40% re-spectively (P = 0.777). Fo r the intermediate grade, the
Table 3 - Characte ristics of patie nts with low grade lymphomas
1st a na lysis 2nd a na lysis
Variables nºpatients P-value nº patients P-value Histologica l subtype
FMSCLC 1 2 0 .0 2 1 1 0 .2 9 Lympho plasmo cyto id 0 3 0 2
Small Lympho cytes 1 2 1 2
Sex
Female 1 1 0 .1 4 1 0 0 .1 9 Male 1 6 1 5
Age (yea rs)
< 6 0 2 4 0 .9 8 2 3 0 .4 5 > 6 0 0 3 0 2
Ra ce
W hite 1 8 0 .2 1 1 7 0 .1 5 Black 0 9 0 8
B Symptoms
Present 2 0 0 .1 0 1 9 0 .0 6 Absent 0 7 0 6
Performa nce Sta tus
0 0 4 0 .2 1 0 4 0 .2 1
1 1 4 1 4
2 0 7 0 5
3 0 2 0 2
4 0 0 0 0
Sta ge
I 0 3 0 .2 6 0 3 0 .2 6
II 0 3 0 3
III 0 7 0 7
IV 1 4 1 4
Ex tra noda l disea se
Present 0 7 0 .6 2 0 5 0 .4 8 Absent 2 0 2 0
Bulk disea se
Present 0 4 0 .6 5 0 4 0 .7 7 0 2 Absent 2 3 2 1
M edia stina l disea se
Present 1 0 0 .2 9 1 0 0 .5 2 Absent 1 7 1 5
CN S involvement
Present 0 2 0 .5 6 0 2 0 .5 6 Absent 1 3 1 3
BM infiltra tion
Present 1 1 0 .9 4 0 8 0 .7 9 Absent 1 6 0 .9 4 1 7
Level of DHL
≤l 2 5 0 U/ dl 0 6 0 .6 9 0 6 0 .6 9 >2 5 0 and <4 5 0 U/ dl 0 8 0 8
≥ 4 5 0 U/ dl 0 5 0 5
Immunophenotype
B 1 8 0 .4 2 1 6 0 .6 0
T 0 3 0 3
N CC = malig nant lympho ma small no ncleaved cell; DSCC = malig -nant lympho ma diffuse small cleaved cell; DMSLC = malig -nant lym-pho ma diffuse mixed small and larg e cell; DLC = malig nant lymlym-pho ma diffuse larg e cell; FMSCLC = malig nant lympho ma fo llicular mixed small cleaved and larg e cell; BM = bo ne marro w
Table 2- Characte ristics of patie nts with inte rme diate grade lymphomas
1st a na lysis 2nd a na lysis
Variables nºpatients P-value nº patients P-value Histologica l subset
DSCC 2 6 0 .2 2 2 0 0 .5 4 DMSLC 2 1 1 7
DLC 1 8 1 5
Sex
Female 3 4 0 .2 9 2 8 0 .2 5 Male 3 1 2 4
Age (yea rs)
< 6 0 4 7 0 .9 6 4 1 0 .1 3 > 6 0 1 8 1 1
Ra ce
W hite 4 3 0 .0 9 3 4 0 .6 8 Black 2 2 1 8
B Symptoms
Present 4 3 <0 .0 1 3 4 <0 .0 1 Absent 2 2 1 8
Performa nce sta tus
0 0 9 <0 .0 1 0 6 0 .0 2
1 3 8 3 3
2 1 4 1 1
3 0 2 0 2
4 0 2
Sta ge
I 0 2 0 .4 2 0 1 0 .2 9
II 1 9 1 7
III 1 6 1 2
IV 2 8 2 2
Ex tra noda l disea se
Present 3 4 0 .4 8 3 0 0 .3 6 Absent 3 1 2 2
Bulk disea se
Present 3 9 0 .1 1 3 0 0 .0 7 Absent 2 6 2 0
M edia stina l Disea se
Present 2 0 0 .8 7 1 8 0 .6 5 Absent 4 5 3 4
CN S involvement
Present 0 4 <0 .0 1 0 4 <0 .0 1 Absent 3 9 3 9
BM Infiltra tion
Present 2 4 0 .1 7 3 6 0 .0 9 Absent 4 0 1 6
Level of DHL
≤l 2 5 0 U/ dl 1 4 0 .0 6 1 0 0 .1 4 >2 5 0 and <4 5 0 U/ dl 2 7 2 4
≥ 4 5 0 U/ dl 1 2 0 9
Immunophenotype
B 3 1 0 .5 0 2 3 0 .2 4
T 0 7 0 5
rate o f CR to the pro to co ls analyzed were: CHOP 61%,
BACOP 41% and MACOP-B 50% (P = 0.1642). The
me-dian 5-year survival rates were: OS 62% and DFS 52% fo r high grade lympho ma, 57% and 49% fo r intermedi-ate grade and 63% and 52% fo r lo w grade lympho ma respectively.
DISCUSSION
We analyzed patients with NHL divided into three subgro ups in acco rdance with the WF classifica-tio n and evaluated the variables that co uld demo n-strate pro gno stic value. A seco nd statistical study was do ne to check the influence o f treatment o n the sur-vival fo r each variable studied at the first step.
The intermediate grade lympho mas presented results co mparable to tho se described in the litera-ture, pro bably because this was the largest gro up o f patients. In this gro up the variables asso ciated with wo rse pro gno sis were: B sympto ms (P< 0.01); perfo r-mance status III and IV (P< 0.01) and CNS invo lve-ment (P = 0.006). There are repo rts that patients with a diagno sis o f perfo rmance status o f III and IV is re-lated to high cell pro liferatio n and this fact co uld have implicatio ns o f an unfavo rable pro gno sis.14 It is well
kno wn that better therapeutic results are asso ciated with lo nger survival in patients that have a go o d per-fo rmance status at the diagno sis.5-7,13
Invo lvement o f the CNS generally implies fre-quently relapsing disease.15 So me studies have
sug-gested that patients with bo ne marro w invo lvement have a higher risk o f presenting CNS infiltratio n.15 This
aspect was o bserved in o ur study.
The small number o f patients with high and lo w grade lympho mas made it impo ssible to demo nstrate statistically so me impo rtant variables repo rted else-where such as: bo ne marro w and CNS invo lvement, bulk disease, mediastinal disease, high levels o f LDH and age abo ve 60 years.15
Fo r high grade lympho mas the fo llo wing vari-ables were related to wo rse disease: yello w race (P = 0.003), ECOG III and IV (P < 0.01) and extrano dal dis-ease (P < 0.01). After including the treatment, the o nly variable asso ciated with an unfavo rable pro gno sis fo r survival was CNS infiltratio n (P < 0.01). Many repo rts have demo nstrated that extrano dal disease, especially if there are two o r mo re invo lved sites, is asso ciated with wo rse evo lutio n.3,16
This is valid fo r all kinds o f lympho mas. This fact, even if negated by o thers, makes us think that it may be necessary to have o ther facto rs asso ciated with the extrano dal disease in o rder to cause a wo rse pro gno sis.5,6 Fo r lo w grade lympho mas,
o nly the lympho plasmo cyto id subset(P = 0.018) had pro gno stic value, and in the seco nd study no variable was asso ciated with treatment and survival.
The o verall survival and DFS fo r all grades o f the WF classificatio n are quite similar to tho se o f o ther studies, altho ugh o ur patients were treated with dif-ferent no n-rando mized pro to co ls. Co sta et al.7 had an
OS o f 54% and a 5-year DFS o f 52% in a series o f 54 high and intermediate grade lympho mas, mo st o f which with diffuse histo lo gical patterns and advanced stage disease. Klimo & Co nno rs17
fo und a median 8-year survival o f 62% and a DFS o f 52% in 126 patients with diffuse large cell lympho ma. Fo r the lo w-grade lympho ma, the OS and DFS were co mparable to the many o ther studies that included patients with ad-vanced stage disease.3
A relatio nship between a high level o f LDH and a wo rse survival fo r NHL has ve ry o fte n b e e n re -po rted.5,14,18 Schneider et al.21 po inted o ut the impo
r-tance o f this marker even when no t co nsidering the extent o f the tumo r no r the bulk mass burden.In o ur intermediate gro up, an LDH higher than 450U/dl had so me relatio n with survival, with a p-value clo se to significance (P = 0.055).
Bo ne marro w invo lvement was no t related to unfavo rable survival in the three studied gro ups. We analyzed the presence o r absence o f fo cal o r diffuse infiltratio n. Fo r the intermediate grade lympho mas, there was a tendency to wards diffuse marro w invo lve-ment and wo rse survival (P = 0.086). Data fro m the Natio nal Cancer Institute, Bethesda, USA, has po stu-lated that marro w invo lvement means a po o r pro g-no stic facto r fo r survival. A similar analysis perfo rmed at the M.D. Anderso n Ho spital was no t able to predict this variable as an unfavo rable facto r. Ho wever, the asso ciatio n o f bo ne marro w invo lvement, high LDH level and a high rate o f cellular pro liferatio n seems to have so me pro gno stic meaning.14 In bo th o f o ur
sta-tistical analyses immuno lo gical pheno typing did no t
Table 4- Distribution of 93 patie nts with non-hodgkin lymphomas according to the tre atme nt re ce ive d
Lymphoma gra de High Intermedia te Low
Maco p-B 6 1 4 4 Pro mace-CytaBO M 1 7 3 BFM-8 3 1 3 3
MVPP 1 1 2 2
BACO P 2 1 3 8
CHO P 5 2 2
Tota l 1 6 5 2 2 5
influence the survival o f the three different gro ups. Our treatment was based o n the first histo lo gi-cal WF classificatio n, but 43 o f the 113 evaluated pa-tients fro m the first study had their histo lo gical sub-type changed after review. Thus, the philo so phy o f bas-ing treatment o n the initial diagno sis generated a mis-cellany o f analyses. Despite having a small sample size, especially when analyzing each chemo therapy scheme in iso latio n, o ur data are similar to tho se in o ther re-po rts.8,20 Altho ugh MACOP-B seems to be better than
CHOP fo r CR rates, we can co nclude that they are simi-lar when co nsidering OS and DFS. This co nclusio n has been co nfirmed by o ther repo rts in the last five years.21
Fo r the largest gro up, the intermediate lympho -mas, there were no differences between CHOP, BACOP and MACOP-B relating to survival (P = 0.1642). When co nsidered separately, CHOP sho wed a better rate o f CR, 8/13 (61.50%), b ut this was no t significant. At present, there is a wo rld trend to use CHOP as the treatment schedule fo r aggressive lympho ma due to results that are similar and co mparable to mo re to xic third-generatio n pro to co ls.7,8,13
Fo r lo w-grade lympho mas o ur results are slightly inferio r to tho se o f o ther repo rts, but are co mparable
to studies that included advanced stage disease.22
Even tho ugh 28% o f tho se patients were treated with third-generatio n schemes and the o thers with CHOP, BACOP, MVPP o r COP, no chemo therapy scheme was seen to be superio r in relatio n to the pro gno sis (P = 0.2717).New treatment fo rms are being used fo r lo
w-grade lympho mas, especially purine analo gs, inter-fero n and allo geneic and auto lo go us bo ne marro w transplantatio n. Ho wever their efficacy is still limited when co mpared with classic treatments such as usag e o f alkylatin g usag e n ts o r usag g re s s ive c h e m o -therapy.23,24 We believe that new studies and pro to
-co ls are necessary in o rder to have a mo re precise -co n-clusio n abo ut the best treatment fo r lo w grade lym-pho mas.25
A new attempt at classifying NHL has recently b een made. In this new classificatio n, lympho pro -liferative diso rders are divided into B, T o r NK dis-eases.26 The cyto genetic characteristics and o nco
gen-esis with their respective mo lecular rearrangements are co nsidered in trying to describe each kno wn pa-tho lo gy as an iso lated entity. It is designated the REAL classificatio n, signifying a co nsensus between Ameri-can, Euro pean and Asian hemato -patho lo gists. This classificatio n appears to have achieved the ideal, but mo re time and experience will b e req uired b efo re reaching a definitive co nclusio n o n such a co mplex subject.
It is clear that we need to bring to gether clinical hemato lo gists, patho lo gists and cyto geneticists in Brazil, in o rder attain a better understanding o f the co mplex setting o f this disease. Co o peratio n between institutio ns in different areas o f the co untry co uld achieve clinical and therapeutic results. Only in this way will there be a co mmo nality o f spirit leading to a better understanding o f NHL in Brazil.
REFERENCES
1. Carb o ne PP, Kaplan HS, Mussho ff K. Repo rt o f the co mmittee o n Ho dgkin’s disease staging. Cancer Res 1971;31:1860-1.
2. Ro senberg SA. Validity o f Ann Arbo r staging o f the no n-Ho dgkin’s lympho mas. Cancer Treat Rep 1977;61:1023-7.
3. Ro maguera JE, McLaughlin P, No rth L, et al. Multivariate analysis o f pro gno stic facto rs in stage IV fo llicular lo w-grade lympho ma: a risk mo del. J Clin Onco l 1991;9:762-9.
4. Velasquez WS, Jagannath S, Tucker SL. Risk classificatio n o f the basis fo r clinical staging o f diffuse large cell lympho ma derived fro m 10-year survival data. Blo o d 1989;74:551-7.
5. Vito lo U, Bertini M, Brusamo lino E, et al. Maco p-B treatment in diffuse large-cell lympho ma: identificatio n o f pro gno stic gro ups in an Italian multivariate study. J Clin Onco l 1992;10:219-27.
6. Shipp MA, Harringto n DP, Klatt MM, et al. Identificatio n o f majo r pro gno stic subgro ups o f patients with large-cell lympho ma treated with m-Baco d o r M-Baco d. Ann Intern Med 1986;104:757-65. 7. Co sta AM, Fro imtchuk MJ, Ro bino wits M, Olivetto LO, Allanse Gil RA.
Lo ng-term results with Maco p-B in the treatment o f aggressive no n-Ho dgkin lympho mas. Am J Clin Onco l 1994;17:323-7.
8. Summary and Descriptio n o f a Wo rking Fo rmulatio n fo r Clinical Usage: Natio nal Cancer Institute spo nso red study o f classificatio n o f no n-Ho dgkin’s lympho mas. Cancer 1992;49:2112-35.
9. Pilleri AS, Sabatini E, Falini B. Immuno histo chemical detectio n o f the m ultidrug transpo rt pro te in P-170 in hum an no rm al tissue s and malignant lympho mas. Histo patho l 1991;19:131-40.
10. Lo ngo D, DeVita VT, Duffey P. Rando mized trial o f Pro mace-Mo pp (PM) (day 1 and 8) vs. Pro mace-CytaBOM (PC) in stage II to IV aggressive no n-Ho d gkin’s lym p ho m a. Pro c Am So c Clin O nc o l 1987;6:206 (abstract).
11. Ho elzer ET, Lö ffer H, Bo denstein H, et al. Intensified therapy in acute lympho blastic and acute undifferentiated leukemia in adults. Blo o d 1984;54:38-47.
12. Yi PI, Co leman S, Saltz L, et al. Chemo therapy fo r large-cell lympho ma: a status update. Semin Onco l 1990;17:60-73.
13. Yo ung RC, Lo ngo DL, Gladstein E, et al. The treatment o f indo lent lym p ho m as: watc hful waiting fo r aggre ssive c o m b ine d m o d ality treatment. Semin Hemato l 1988;25(suppl 2):11-6.
15. Silvestrini R, Co sta A, Bo racchi P, Giardini R, Rilke F. Cell pro liferatio n as a lo ng term pro gno stic facto r in diffuse large-cell lympho mas. Int J Cancer 1993;54:231-6.
16. Jagannath S, Velasquez SW, Tucker SL, et al. Tumo r burden assessment and its implicatio n fo r a pro gno stic mo del in advanced diffuse large-cell lympho ma. J Clin Onco l 1986;4:859-65.
17. Shipp AM, Yeap YB, Harringto n DP, Klatt MM, et al. The m-Baco d co mbinatio n chemo therapy regimen in large-cell lympho ma: analysis o f the co mplete trial and co mpariso n with the M-Baco d regimen. J Clin Onco l 1990;8:84-93.
18. Kirn D, Mau c h P, Sh affe r K, Pin ku s G, e t al. Larg e - c e ll an d immuno blastic lympho ma o f the mediastinum: pro gno stic features and treatment o utco me in 57 patients. J Clin Onco l 1993;11:1336-43. 19. Klimo P, Co nno rs J. MACOP-B chemo therapy fo r the treatment o f
diffuse large-cell lympho ma. Ann Intern Med 1985;102:596-602. 20. Danie u L, Wang G, Ko zine r B. Pre dictive m o de l fo r pro gno sis in
advanced diffuse histio cytic lympho ma. Cancer Res 1986;46:5372-9. 21. Schneider RF, Seibert K, Passe S. Pro gno stic significance o f serum lactate
dehydro genase in malignant lympho ma. Cancer 1980;46:139-43. 22. Miller TP, Lippman SM, Spier CM. HLA-DR (Ia) immune pheno type
predicts o utco me fo r patients with diffuse large-cell lympho ma. J Clin Immuno l 1988;82:370-2.
23. Go rdo n LE, Harringto n D, Andersen R, et al. Co mpariso n o f a seco nd generatio n co mb inatio n chemo therapy regimen (m-Baco d) with a s tand ard re gim e n ( Cho p ) fo r ad vanc e d d iffus e no n- Ho d gkin’s lympho ma. N Engl J Med 1992;327:12-8.
24. Lyang R, Chiu E, Lake SL. Management o f lo w-grade lympho mas in Ho ng Ko ng Chinese. Onco lo gy 1991;48:121-4.
25. Mc Ke lve y EM, Go ttlie b JA, Wils o n HE. Hyd ro xyd au n o m yc in (adriamycin) co mb inatio n chemo therapy in malignant lympho ma. Cancer 1976;38:1484-93.
26. Po rtlo ck CS, Ro senberg SA. No initial therapy fo r stage III and IV no n-Ho dgkin lympho mas o f favo rable histo lo gic types. Ann Intern Med 1979;90:10-3.
27. Cheso n B. New chemo therapeutic agents fo r the treatment o f lo w grade no n-Ho dgkin’s lympho mas. Semin Onco l 1993;20(suppl 5):96-110. 28. Chan JKC, MBBS, Banks PM, Cleary ML, et al. A revised Euro
pean-Ame rican classificatio n o f lympho id ne o plasms pro po se d b y the internatio nal lympho ma study gro up: a summary versio n. Am J Clin Patho l 1993;103:543-60.
r e s u m o
CO N TEX TO : N a do e nç a de Ho dg kin, c a da e stá g io c línic o o u pato ló g ico po de ser relacio nado co m a extensão da área envo lvida e predizer a pró xima reg ião anatô mica de risco para disseminação .
OBJETIVO: Estabelecer o s fato res pro g nó stico s que melho r predizem so brevida em LN H.
TIPO DE ESTUDO: Estudo retro spectivo
LOCAL: Disciplina de Hemato lo g ia e Hemo terapia, Universidade Fed-eral de São Paulo - Esco la Paulista de Medicina.
PARTICIPAN TES: 1 4 2 pacientes co m LN H diag no sticado s entre fevereiro de 1 9 8 8 e março de 1 9 9 3 .
VARIÁVEIS ESTUDADAS: Tipo histo ló g ic o , sexo , ida de, ra ç a , sinto ma s, sita ç ã o “ pe rfo rma nc e ” , e stá g io , do e nç a e xtra no da l, d e se nvo lvime nto d e Bulk, c o mp ro me time nto me d ia stina l, e nvo lvime nto d o SN C , infiltra ç ã o d a me d úla ó sse a , níve l d e desidro g eno se láctica, fenó tipo imune.
RESULTADOS: Ao primeiro estudo (1 1 3 pacientes), as seg uintes variáveis tiveram uma pio r influência na so brevida: raça amarela (P<0 .1 ); ECO G II, III e IV (P<0 .1 ) e do ença extrano dal (P<0 .1 ) para o s linfo mas de alto g rau; sinto mas co nstitucio nais (P<0 .1 ), ECO G II, III e IV (P<0 .1 ) e envo lvimento de SN C (P<0 .1 ) para o s linfo mas de g rau intermediário e o subtipo linfo plasmo citó ide (P=0 .0 1 8 6 ) para o s linfo mas de baixo g rau. Ao seg undo estudo (9 3 pacientes), quando inclui-se o tratamento , as variáveis relacio nadas a so brevida fo ram : envo lvimento de SN C (P<0 .1 ) para o linfo mas de alto g rau; sinto mas co nstitucio nais (P<0 .1 ), ECO G II, III, IV (P=0 .0 1 8 5 ) e envo lvimento de SN C (P<0 .1 ) para o g rupo intermediário . N enhuma variável relacio no u-se co m a so brevida para o s linfo mas de baixo g rau.
CON CLUSÕES: O s linfo mas de g rau intermediário , pro vavelmente devido ao maio r número de pacientes, fo ram mais co mpatíveis co m o s d a d o s e nc o ntra d o s na lite ra tura . N e ste c a so e sp e c ífic o , o tratamento não influencio u a so brevida.
PALAVRAS-CHAVE: Linfo ma nã o -Ho dg kin. Fa to res pro g nó stico . So brevida.
Karin Zattar Ce cyn, MD. Assistant Physician, Discipline o f Hemato lo gy and Hemo therapy, Universidade Federal de São Paulo /Esco la Paulista de Medicina, São Paulo , Brazil.
José Salvador Rodrigue s de Olive ira, MD, PhD. Adjunct Pro fesso r, Discipline o f Hemato lo gy and Hemo therapy, Universidade Federal de São Paulo /Esco la Paulista de Medicina, São Paulo , Brazil.
Antônio Corre ia Alve s, MD, PhD.Adjunct Pro fesso r, Discipline o f Anato my Patho lo gic, Universidade Federal de São Paulo /Esco la Paulista de Medicina, São Paulo , Brazil.
Maria Re gina Re gis Silva, MD, PhD.Adjunct Pro fesso r, Discipline o f Anato my Patho lo gic, Universidade Federal de São Paulo /Esco la Paulista de Medicina, São Paulo , Brazil.
José Ke rbauy, MD, PhD. Titular Pro fesso r, Discipline o f Hemato lo gy and Hemo therapy, 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: 4 March 1999.
Acce pte d: 14 July 1999
Addre ss for corre sponde nce :
Karin Zattar Cecyn
Universidade Federal de São Paulo /Esco la Paulista de Medicina, Disciplina de Hemato lo gia e Hemo terapia.
Rua Napo leão de Barro s, 715 São Paulo /SP - Brasil - CEP 04023-902 e-mail: cecyn@ uo l.co m.br
