The significance of TDT-positive subpopulations in MDS

Second International

Conference on Myelodysplastic Syndromes

micJ!Im RBLRVMUX OF DImIA!lXa OF a BLBSTS WITHQ&CM MD 1,25_DIMDttOXY-

31

BONE MARROW TRANSPLANTATION (BMT) FOR MYELODYSPLASIA (MDS): WITH ALTERNATIVE PREPARATION BUSULFAN/CYCIX3PHOSPHAMIDE (BUKY)

VITAMIND3 (W). SM Kelsey, HW Makin, AC Newland. Departments of Haematology and Chemical Pathology,The Royal London Hospital,El1BB.

M.R.O'Donnell', N.J. Chao*, G.M.Schmidt’, KG. Blume’, S.J. Forman’ City of Hope, Duarte, CA’ and Stanford University, Stanford, CA2 BMT Teams

We studied the effect of vitamin D3 and GM-CSF on mon0cyti.c differentiation of AI% blasts. Blasts from 21 patients with AML were cultured for 4 days with D3, GM-CSF or both in combination. D3 induced phenotypic differentiation in 14/21 (67%) of blast populations, as shown by expressionof the mono&e-associated antigen CD14. GM-CSP had little effect alone;however,in7 (33%) cases it acted with D3 to further increase CD14 expressionover that seen with D3 alone. D3 and GM-CSF, alone or combined, had little effect on expressionof the functionalantigens CR3 (CDllb)or PcR2 (CD32). In addition, there was no overall increase in functional activationof blasts, as assessedby phagocytosis of bacteria or respiratory burst in response to PMA. Both expressionof CD14 and FcR2 correlatedstronglywith functional activation of blasts. We conclude that GM-CSF and D3 may act in synergy to increase phenotypic,but not necessarilyfuncof differentiation in a tional, aspects proportionof AML blast populations.

Alternatives to radiation in pre-BMT myeloablation are desirable especially in older pts. with MDS who often have prior toxic exposures. Since 1986,25 pts. (median age 36 yrs., range S-50 yrs.)with MDS (9RAEB,5 RAEBIT, 2'MDS, 5 myelofibrosis and 1 RA) received BU 4 mgkg/day and CY 60 mgkg/day as preparation for BMT, 22 received BU x 4 daysandCY x 2 dayswhile 3 received BU x 3 days and CY x 3 days. All pts. received CSA and prednisone as graft vs. host disease (GVHD) prophylaxis. The regimen was well tolerated with minimal mucositis; all pts. have engrafted. Currently, 11 pts. are alive and well at 2-31 months. ‘lko pts. (8%) died of acute regimen related complications (1 venocclusive disease and 1 aspergillosis) and 10 (40%) have died of late post BMT complications (6 GVHD, 1 sepsis, 1 aspergillosis, 1 CMV pneumonia, 1 GI bleed). Two pts. have relapsed at +2 and +22 months, with a median follow-up of one yr. Projected relapse rate at 3 yrs. is 39%. The KaplanMeier product limit estimate of relapse free survival is 28%. These results are comparable to those for radiation regimens which have acute regimen related mortalities of lo-25% and relapse free survivals of 25-45% in similar pt. populations.

m~~-cc-QlDsSIGNIFICANCE OF Tm!-RXITIVE h)ImoANLHrmmE-TImam~m sDBpuAlIwIwKsIN=Pmcl?mINm M.R. Schipperus, H.J. Adriaansen, K. van JAL;wps:-AHDJ. Lom, A. Hagemeijer. Departments of J.P. IJWXIE, F. ISWD, L. EWIWW, N. m,

TEE

Hematology and Immunology, Academic Hospital and Cell Biology and Genetics,

Erasmus University Netherlands.

Rotterdam,

The

Recently, we have demonstrated by double immunofluorescence(DIF) analysis, that a terminal deoxynucleotidyl transferase-myeloid-antigen doublepositive(MM+/TdT+)leukemic subpopulation occurs in the majority of acute myeloid

1euJcemias(AMLs). In this study six patients with a MDS (3 FURS, 2 RAEB and 1 RAEBt) and 2 patients with a AML following a MDS phase (LT-MDS) were studied for the presence of TdT and CD13, CD14, CD15 and CD33. TdT expression was found in 0.1 - 61% of the cells. In the RARS cases 0.02 - 4.7%,in the RAEB(t) cases 0.01 - 11% and in the LT-MDS cases 4 - 53% MM+/TdT+ cells were found.

Follow-up studies performed in two patients showed an increase of MM+/TdT+ Cell9 from 11% in RAEBt to 25% in AML phase and from 0.1% in RAEB to 35% in AML phase respectively. These data indicate that small numbers of MM+/TdT+ cells are already detectable in MDS and this subpopulation of abnormal cells increases

with disease progression.

VAN m AKKR N.C. WUN, A. NhlHRU - flijpital ST AISFDINE, PARIS-FWAKE . . A crmbinaticn of mitoxanti 0 and daur~&

(INR) with vimis tirle~them~a)hasbeen~ in refracts acute to the effective

myeloblastic leukfka in &lilts wa) (cs 1988,22, 344-347). In this study there was DD major cardiotcnticity. We tkrefore examina&dtheeffectiveoessoftheD(Hinthekeatment ofHD8wbichhavebeentransfozuedinNlL.15carsecUive patients (pts) witha median of qe of 58 ans (44-65) Entered the StuQ. 7/l3 pts studied bad Wyotypic almzm&ties. D@uks of WDSwas taade 0.5 to 13 years beforetransforaattiafAM,oaXred.IberXNregimmwas deliveredwerapexiodof6&ys:vimistine2~I.V. m, m 45~/maQIaio~24, mz 12 ~jti I.V.(11says 2-6.mXwasinfusedlbafte.rDHIwhengiventhesame Qy.‘Ibeoedianduraticoofap1asia~29days(21-50). After ooe single aan.-se of therirpy, 8 pts (53 %) achieved am. Ibe&iandura&mofCXwas88ths (4,30). H&rate cardiac failure was observed in 2 pts. For the othrpts,weaidnot-aDycbangeinIxx;ar liidcadographic pelf-. 3ptslmdementautol~ bme manuf transplantatico 0 with meby

mafcsftide, while in CR (2) or in PR (l), 1 is presently alive~uellatlyear.Wefurthfzamfirmtheefficacy of a ambjaatico of 2 intercalatirg agents in the treamt of malignant hemopathies of the n@oid ,zGt mym” tid not lppclude Wt