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Autologous stem cell transplantation for acute myeloid leukemia - a 15-year single center experience

Incidence of FLT3 Internal Tandem Duplication in Acute Promyelocytic Leukemia

U radu se iznose rezultati liječenja nacionalne skupine za dječju hematologiju djece oboljele od akutne limfatičke leukemije u Hrvatskoj u vremenskom periodu od 1.10.1996. do 31.12.2000. godine.Postignuti rezultati liječenja dječjih ALL prema ALL-BFM95 protokolu, gotovo su isti kao i rezultati koji se postižu u vodećim europskim centrima za liječenje djece oboljele od akutne limfatične leukemije.

From 1995 until 2003, seventy six de novo acute myelogenous leukemia samples undertaken at the time of diagnosis were examined. Response therapy in the group of patients with 3q abnormalities was poor. These findings suggest that 3q rearrangements might have unfavorable prognosis for adult patients with de-novo acute myelogenous leukemia.

U radu se iznose rezultati liječenja nacionalne skupine za dječju hematologiju djece oboljele od akutne limfatičke leukemije u Hrvatskoj u vremenskom periodu od 1.10.1996. do 31.12.2000. godine.Postignuti rezultati liječenja dječjih ALL prema ALL-BFM95 protokolu, gotovo su isti kao i rezultati koji se postižu u vodećim europskim centrima za liječenje djece oboljele od akutne limfatične leukemije.

FLT3 is a receptor tyrosine kinase expressed by immature hematopoietic cells. This receptor is important for the normal development of stem cells and immune system. Mutations of FLT3 have been detected in about 30% of patients with acute myelogenous leukemia, most often involving small tandem duplications (FLT3 ITD) of amino acids within the juxtamembrane domain of the receptor. Studies suggest that mutant FLT3 cooperates with other leukemia oncogenes to confer a more aggressive phenotype. The aim of this study was to determine the prevalence of FLT3 ITD in de novo diagnosed AML/MDS patients and the association of FLT3 ITD with specific FAB subtypes and, possibly, to correlate the presence of mutation with cytogenetics. One hundred consecutive adult cases (age 22 – 78 yrs.) of de novo AML and MDS were studied. Acute promyelocytic leukemia patients were excluded. RNA obtained from leukemic samples at diagnosis was employed in RT-PCR analysis with primers according to Nakao et al. Leukemia 1996. The presence of ITD was detected as an increase in the size of the PCR product. Among all samples tested, FLT3 ITD was found in 21 cases (21%). The presence of FLT3 ITD was the highest in FAB M2 subtype (12/30 - 40%) but all 12 patients with FLT3 ITD present were negative for AML1/ETO transcript ; FLT3 ITD was found in 3 out of 13 cases of FAB M5 subtype (23%) and in none of 23 cases with MDS. These results confirm the presence of mutation only in AML, compared to MDS and the higher prevalence of mutation in patients with normal karyotype.

Near-tetraploidija nađena je u 2 pacijenta s neuobičajenim imunofenotipom (bifenotipska AL i T ALL s mijeloidnim i NK biljezima). Budući da je tetraploidija u AML obično vezana za sekundarnu klonsku evoluciju (posebice u M2), u opisanih se bolesnika vjerojatno radi o izvornom leukemijskom klonu.

Na Zavodu za hematologiju i onkologiju Linike za pedijatriju KBC Zagreb referentnom ventru Ministarstva zdravstva RH za dječju hematologiju i onkologiju od 1990-2000 godine liječeno je 12 djece s T-NHL s protokolom NHL-BFM. Postignuti rezultati liječenja su vrlo dobri i ne razlikuju se od rezultata koje postižu slični europski centri za dječju hematologiju i onkologiju.

U radu je ispitana zastupljenost pojedinih vrsta AL. Dodatno je ispitan značaj imunofenotipskih kategorija u odnosu na odgovor na liječenje, preživljenje bez znakova bolesti i ukupno preživljenje.

Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), in advanced stage of disease, is resistant to standard chemotherapy. Imatinib was found to be effective in these patients. This paper shows our preliminary results. Imatinib mesylate was given to 15 patients during a 9-month period. Nine of them were in accelerated phase and 6 in blastic crisis of Ph+ CML. Patients were evaluated for hematologic and cytogenetic responses. Imatinib mesylate induced complete haematologic response in 12 patients (80% and cytogenetic response in 8 patients (53%). Six patients (40%) had a major cytogenetic response. After a 9-month follow up Ph+ CML progressed in 9 patients (60%) and 4 of them died. The most frequent adverse effects were edema, nausea, neutropenia and thrombocytopenia. Imatinib mesylate has a substantial, but short term activity in the accelerated phase and blastic crisis of the Ph+ CML.

U ovom radu iznose se rezultati liječenja nacionalne grupe za dječju hematologiju djece oboljele od akutne limfatičke leukemije u Hrvatskoj. Postignuti rezultati su gotovo isti kao i u vodećim europskim centrima za liječenje djece oboljele od akutne limfatičke leukemije.

In this study the expression pattern of HOXA9 in cell samples collected from patients with hematological malignancies was investigated. By using RT-PCR we analyzed the expression of HOXA9 in 36 AL samples (14 AML, 12 ALL and 10 mixed or biphenotypic AL - BAL), 4 B-CLL, several leukemia cell lines (K562, HL60, SU-DHL4 and NALM-6) as well as in control samples from healthy donors (peripheral blood and bone marrow mononuclear cells, PBMNC and BMMNC, respectively). In contrast to PBMNC, HOXA9 was found in bone marrow MNC of a healthy donor. In acute leukemia, HOXA9 was expressed in 79% (11/14) of AML, 60% (6/10) of BAL and, the most interesting finding, in 15% (2/12) of ALL samples. In relation to FAB and/or immunophenotype, HOXA9 was present in 1/2 FAB-M1, 2/4 FAB-M2, 2/2 FAB-M3, 3/3 FAB-M4, 2/2 FAB-M5a and in one FAB-unclassified MPO+CD13+ AL. Among ALL patients, HOXA9 was expressed in 0/4 T-ALL, 1/1 pro-B, 0/6 "common" -ALL, and 1/1 B-ALL whereas in biphenotypic AL the HOXA9 message was present in 1/1 FAB-M1, 0/2 FAB-M5a, 2/4 FAB-L2, 2/2 FAB-UAL and in 1/1 biclonal BAL. Among the cell lines tested, HOXA9 was found in cells with myeloid differentiation (HL60 and K562), but also in pre-B cell line NALM6. Although preferentially expressed in leukemic cells with myeloid commitment, the expression of HOXA9 in B-lineage ALL is consistent with its finding in pre-B cell line NALM6. Further studies are needed to correlate leukemia HOXA9 gene expression with biological and clinical behaviour of AL.

The expression of cyclin A1, a cell cycle regulatory protein, has been documewnted in normal human hematopoietic progenitor cells and in the majority of myeloid and undifferentiated hematological malignancies.In this work we extended this observation by analysing the expression of cyclin A1 in 38 acute leukaemias of myeloid, lymphoid and mixed lineage leukaemias in children and adults.

From 1988 to 1998 one hundred forty eight patients with acute lymphoblastic leukemia (ALL) were enrolled into prospective study. The aim of the study was to evaluate efficacy of common treatment for acute lymphoblastic leukemia and to determine risk factor for outcome. Out of 148 patients, 31 (21%) had acute nondifferentiated leukemia (according to the FAB criteria) with expression of lymphoid markers. Those patients were treated in the same way as patients with ALL. According to the type of consolidation therapy patients were divided into three groups. Chemotherapy alone received 38 (38%) patients, and 30 (31%) patients received autologous stem cell transplantation (SCT) or allogeneic STC. There were no statistical difference in sex, age, FAB subtype, number of WBC and platelets in the time of diagnosis and incidence of cytogenetic abnormalities between these three groups. Median follow-up for chemotherapy group was 68 (range 12-98) months, for allogeneic SCT 102 (range 12-120) and for autologous SCT 99 (range 12-105) months. As a condition regimen the majority of patients treated with SCT received total body irradiation followed by cyclophosphamide. There was statistically significant difference in the source of stem cell for transplantation: in 20% of autologous SCT peripheral blood was used as source of stem cells. Relapse rate was significantly higher in patients receiving chemotherapy alone than in patients receiving either autologous or allogeneic SCT (83 vs. 45 vs. 27%, p

Analiza citomorfološkog razmaza koštane srži i citokemijske karakteristike zloćudnih stanica osnova su dijagnoze tipa akutne leukemije, prema FAB klasifikaciji. Imunofenotipizacija u protočnom citometru, konvencionalna citogenetika, fluorescentna in situ hibridizacija (FISH) te molekularna analiza genoma stanice PCR metodom (engl. polymerase chain reaction) daljnji su dijagnostički postupak. PCR je neizostavna metoda pri otkrivanju minimalne ostatne bolesti, jer može otkriti vrlo malen broj zloćudnih stanica u koštanoj srži, kada se bolesnik nalazi u kompletrnoj morfološkoj remisiji (manje od 5% zloćudnih stanica u koštanoj srži uz uredan nalaz periferne krvi). Takav pristup poboljšava praćenje tijeka bolesti. In situ hibridizacijom (ISH) moguća je promjenu genoma pridružiti specifičnom tipu stanice, no metoda nije dovoljno osjetljiva. Spajanjem PCR i ISH nastaje PCR in situ, metoda povećane osjetljivosti, koja omogućuje umnažanje promjene genoma u intaktnoj stanici u dovoljnom broju kopija. U ovom radu prikazali smo dvije bolesnice, čiji su razmazi koštane srži analizirani i PCR-om in situ.

case report

Na Zavodu za hematologiju i onkologiju Klinike za pedijatriju Šalata liječeno je 38 djece s akutnom limfatičkom leukemijom protokolom ALL-BFM 95 u periodu od 1.01.1995. do 31.12.1998.godine. Prva kompletna remisija postignuta je u 38 bolesnika (100% -33.dan ; u 32/84% -15.dan). Prvi relaps nastao je u 6 (15% ) bolenika (3 hematološki relaps, 1 meningelani relaps, 2 hematološki i meningealni relaps). 30.06.1999. u prvoj kompletnoj remisiji je i dalje 32 (85%) bolesnika ; 3 (8%) bolesnika je umrlo tijekom relapsa, a 3 je u drugoj remisiji. U grupi standardog rizika u prvoj kompletnij remisiji je 90%, u grupi sredjeg rizika 86%, a u grupi visokog rizika 40% bolesnika. Postignuti preliminarni rezultati potvrđuju vrijednost protokola ALL-BFM 95 u liječenju djece s akutnom limfatičkom leukemijom.

Miješane ili bifenotipske akutne leukemije (BAL) jesu rijetki (

This study is an evaluation of the frerquency and efficacy of GVHD induced by cyclosporine A(CyA) after ABMT. The study confirmed that GVHD could be induced by CyA after ABMT. In our study this was observed in one third of patients. This GVHD was mild, selfmited and did not require any treatment. The autotoxicity in patients with AML was documented in vitro by CMLA

Od 1987. do 1995. godine u istraživanje je uključeno 110 bolesnika s novo-otkrivenom akutnom mijeloičnom leukemijom. Za analizu kromosoma primjenjene su standardne metode G i R pruganja. Prema nalazu citogenetske analize bolesnici su razdijeljeni u tri prognostičke skupine. Bolesnici s translokacijom t(8 ; 21), inverzijom inv(16), translokacijom t(15 ; 17) i trisomijom 21 nalaze se u tzv. povoljnoj skupini. Bolesnici s urednim nalazom bez kromosomskih promjena odnosno bolesnici sa citogenetskim promjenama nepoznate prognoze čine posebnu skupinu intermedijarne prognoze. Bolesnici u kojih je nađena trisomija 8, ili promjene na 5, 7 ili 11 kromosomu nalaze se u nepovoljnoj skupini. Citogenetske promjene utvrđene su u 79 (72%) bolesnika. Povoljan citogenetski nalaz utvrđen je u 30 (27%) bolesnika. Intermedijarni tip citogenetske promjene nađen je u 37 (34%) bolesnika, dok je nepovoljna citogenetska promjena objektivizirana u 43 (39%) bolesnika. Kompletna remisija postignuta je u 81% bolesnika dobre citogenetske prognoze, u 65% bolesnika intermedijarne citogenetske prognoze, te u samo 37% bolesnika nepovoljne citogenetske prognoze (p=0.001). Vjerojatnost petogodišnjeg preživljenja bez znakova bolesti u bolesnika s povoljnom, intermedijarnom i nepovoljnom citogenetskom promjenom iznosi 40%, 30% i 5% (p=0.05). Vjerojatnost relapsa bolesti iznosi 82% za bolesnike s nepovoljnom citogenetskom promjenom, 68% za bolesnike s intermedijarnom citogenetskom promjenom i 56% za bolesnike s povoljnim citogenetskim nalazom (p=0.05). Prema multivarijatnoj analizi stariji bolesnici s nepovoljnim citogenetskim promjenama, sa AML-M4 i AML-M5 podtipom prema FAB razdiobi, te bolesnici s velikom brojem leukocita i/ili malim brojem trombocita pri dijagnozi imaju veliku vjerojatnost nepovoljnog ishoda liječenja i malu vjerojatnost dugotrajnog preživljenja bez znakova bolesti.

Premda je imunofenotipizacija akutnih leukemija već dugo sastavni dio rutinskog dijagnostičkog postupka, još uvijek postoji neslaganje glede učestalosti i prognostičkog utjecaja imunofenotipskih kategorija, a posebno tzv. miješanih ili bifenotipskih akutnih leukemija (BAL). U ovom radu analizirana je učestalost citomorfoloških (FAB) i imunofenotipskih kategorija, kao i citogenetika 59 akutnih leukemija (AL) u djece liječene u Klinici za pedijatriju Šalata u razdoblju od kolovoza 1995. do prosinca 1998. godine. Od ukupno 59 AL, citomorfološka dijagnoza akutne limfatične leukemije (ALL) postavljena je u 42 (71%) bolesnika, akutne mijeloične leukemije (AML) u 16 (27%) bolesnika, dok su u jednog bolesnika nađene dvije leukemijske linije. Prema imunofenotipu, sve su AL razvrstane u tri skupine: AL bez koekspresije biljega - 40/59 (67.8%), AL s koekspresijom limfoidnih ili mijeloidnih biljega - 11/59 (18.6%), te bifenotipske AL (BAL) - 8/59 (13.6%). U skupini AL bez koekspresije biljega bilo je (prema FAB klasifikacji) 30 ALL i 10 AML, u skupini s koekspresijom biljega bilo je 8 ALL i 3 AML, dok je podjednak udio ALL i AML (4:3) nađen u skupini BAL (uz nalaz jedne biklonske AL). Pri tome, citogentski nalaz nije pokazao značajnu povezanost tzv. nepovoljnih promjena kariograma s imunofenotipski neuobičajenim kategorijama AL. Premda je u ovom istraživanju broj AL s koekspresijom biljega i BAL-a relativno malen u tijeku je dodatna obrada kliničkih parametara kako bi se ispitala njihova povezanost s laboratorijskim nalazima.

Fluorescentna in situ hibridizacija (FISH) tehnika je molekulske genetike koja omogućava direktnu identifikaciju dijelova gena, gena, specifičnih kromosomskih regija i cijelih kromosoma. Metoda omogučava vizualizaciju promjena u ne samo metafaznim kromosomima nego i u interfaznim jezgrama. Metoda FISH temelji se na hibridizaciji dviju komplementarnih sekvenci, što je i jedno od osnovnih načela molekulske genetike. Upotrebom specifičnih proba dobijaju se informacije o genomu. Svaka proba veže se na specifično mjesto na kromosomu (ili cijeli kromosom), te na taj način identificiraju se specifične regije ( npr.centromera ). Za svaki nalaz potrebno je analizirati od 200 do 400 interfaznih jezgara odnosno veći broj metafaza ( ť 25 matafaza). Metodom FISH moguće je objektivizirati i one promjene koje nisu nađene klasičnom citogenetikom. U tu svrhu analizirano je 30 uzoraka koštane srži u bolesnika s akutnom mijeloičnom leukemijom. Klasičnim metodama u 13 (43%) bolesnika nađene su citogenetske promjene. Primjenom metoda FISH specifične citogenetske promjene za određeni tip akutne mijeloične leukemije nađene su u 9 (30%) bolesnika u kojih je nalaz klasične citogenetike bio uredan. FISH moguće je otkriti specifične kromosomske promjene koje nisu bile vidljive klasičnim metodama citogenetike.

Uvod Dijagnostika akutnih leukemija u djece osniva se, kao i dijagnostika leukemija u odraslih, na FAB-klasifikaciji, imunološkoj tipizaciji te citogenetskoj analizi. Analizom naših rezultata željeli smo utvrditi korelaciju FAB subklasifikacije akutnih leukemija djece s imunološkim podtipovima te kromosomskim promjenama. Bolesnici i metode Analizirali smo 79 akutnih leukemija djece prema FAB-klasifikaciji, imunološkom fenotipu te citogenetskom nalazu. Bolesnici su bili mlađi od 15 godina. Rezultati U našoj analiziranoj skupini djece najčešće su nađene akutne limfatične leukemije (84,7%), dok su AML činile svega 15,3% akutnih leukemija u ovoj skupini. Od podtipova ALL najveći postotak činile su L2 leukemije (75,4%), L1 je nađena u 19,5% slučajeva, a najrjeđe se radilo o L3 subtipu. Od AML nađeni su svi podtipovi (od M1 do M8) osim podtipa M4. Koekspresija mijeloidnih biljega u citomorfološki dijagnosticiranih ALL nađena je u 14/57 (25 %) leukemija. U većini leukemija te skupine 12/14 (85%) dijagnosticiran je L2-podtip. U blastima svih leukemija citokemijski određena MPO bila je negativna. Ekspresija CD 34 antigena nađena je u visokom postotku i u L1 i u L2. Citogenetska analiza učinjena je u 57/78 (73,1%) obrađenih leukemija.U 9/57 (16 %) nalaz je bio uredan, u 42/57 (73 %) patološki, a u 6/57 (11 %) kultura nije uspjela. Zaključak U dječjoj dobi nalaze se svi oblici akutnih leukemija, samo što je ALL izrazito češća (AML:ALL=15,3%:84,7%). Od ALL u našem ispitivanju citomorfološki najčešće se nalazi podtip L2. U ALL našli smo visoku učestalost ekspresije mijeloidnog antigena u L2 podtipu uz imunofenotip "common". Korelacija morfoloških osobina blasta u ALL djece u usporedbi s imunološkim fenotipom pokazuje samo jasnu korelaciju morfološkog L3-podtipa i B-imunofenotipa zbog karakterističnih morfoloških osobina blasta u L3.

Acute promyelocitic leukemia M3 is AML subtype characterized by proliferation of malignant promyelocytes with mature myeloid immunophenotype and atypical reciprocal traslocation involving chromosome 15 and 17 (t(15 ; 17)(q22 ; q11)) resulting in the fusion of retinoic acid receptor alpha (RAR alpha) on chromosome 17 and the putative factor PML. There are three M3 morphologic variants: typical hypergranular form, hypogranular and basophilic variant. However, some of patients have not specific translocation, or they have other cytogenetic abnormalities beside or without characteristic ones. The aim of the study was to compare morphologic, immunologic, cytogenetic and molecular characteristic of blasts in 15 patients with M3 treated in Clinical Hospital Zagreb, Zagreb, Croatia. In major M3 patients (13) blasts had typical hypergranular appearance with mature myeloid immunophenotype (HLD-DR-, CD13+, CD33+). Typical translocation t(15 ; 17)(q22 ; q11) was detected by cytogenetic analysis in 5 M3 patients but PML/RARalpha was positive in 11 out of 14 patients with RT-PCR. In one patient t(17 ; 17) was found, in 2 patients with +8 one patient had also add (7)(q22) and -7. Patients with complete remission (13) became PML/RARalpha negative. Four of them reverted to PCR positivity and relapsed within 3 months.

Od 1995. do 1999. godine u istraživanje je uključeno 79 bolesnika u dobi od 15-70 godina s novo-otkrivenom akutnom mijeloičnom leukemijom (AML) ili akutnom limfocitnom leukemijom (ALL). Za analizu kromosoma primjenjene su standardne metode G i R pruganja te metoda fluorescentne in situ hibridizacije (FISH). Akutna mijeloična leukemija. Od ukupno 51 (65%) bolesnika s AML metodama klasične citogenetike kromosomske promjene nađene su u 21 (41%) bolesnika. Od ukupno 30 bolesnika s urednim nalazom primjenom FISH specifične kromosomske promjene nađene su u 13 (43%) bolesnika. Ukupno su u 34 (67%) bolesnika s AML objektivizirane kromosomske promjene, dok je u 17 (33%) bolesnika nađen uredan citogenetski nalaz. U 5 (14%) bolesnika nađena je translokacija t(8 ; 21)(q22 ; q22). U jednog bolesnika uz ovu translokaciju utvrđen je gubitak kromosoma Y, a u jednog bolesnika intersticijska delecija dugog kraka devetog kromosoma. Inverzija inv(16)(p13 ; q22) nađena je u 4 (12%) bolesnika. U jednog bolesnika uz inv(16) utvrđena je i trisomija 21. Od ukupno 5 (14%) bolesnika s AML-M3 translokacija t(15 ; 17) (q22 ; q21) utvrđena je u svih bolesnika. Translokacija t(11q23) nađena je u 7 (21%) bolesnika. U 3 (9%) bolesnika nađene su kompleksne promjene kariotipa. Delecija 5q ili 7q nađena je u 3 (9%) bolesnika, dok je u 2 (6%) bolesnika utvrđen gubitak 5 ili 7 kromosoma. Trisomija 8 utvrđena u 4 (12%) bolesnika, a trisomija 12 u jednog bolesnika. Akutna limfocitna leukemija Od ukupno 28 (35%) bolesnika s ALL metodama klasične citogenetike kromosomske promjene utvrđene su u 9 (32%) bolesnika. Dodatnom FISH u bolesnika s urednim kariotipom specifične citogenetske promjene utvrđene su u 6 (21%) bolesnika. Ukupno su u 15 (54%) bolesnika s ALL objektivizirane citogenetske promjene, dok je u 13 (46%) bolesnika nađen uredan citogenetski nalaz. Hiperdiploidija je nađena u 3 (20%) bolesnika, dok je pseudodiploidija utvrđena u 3 (20%) bolesnika. Translokacija t(8 ; 14)(q24 ; q32) utvrđena je u 2 (13%) bolesnika, dok je translokacija t (9 ; 22)(q34 ; q11) nađena u 4 (27%) bolesnika. U jednog bolesnika nađen je kompleksan kariotip. MLL gen odnosno translokacija t(11q23) utvrđena je u 3 (20%) bolesnika.

Laktoferin je protein koji se nalazi u sekundarnim zrncima zrelijih stanica granulopoeze, koja sadrže još i tri proteina (transkobalamin I, gelatinazu i kolagenazu) i druge komponente. Funkcija laktoferina do danas još nije poznata. U bolesnika s akutnom mijeloičnom leukemijom (AML) uz nezrele maligne stanice često barem dio preostalih zrelih stanica pokazuje neka odstupanja. Tako se citomorfološkom analizom mogu ponekad naći granulociti s “pseudoPelger” anomalijom jezgre ili se citokemijski ili imunocitokemijski nalazi manjak ili nedostatak pojedinih komponenti primarnih ili sekundarnih zrnaca, pa tako i laktoferina. Cilj rada je bio usporediti postotak laktoferin pozitivnih zrelih stanica granulopoeze u koštanoj srži u bolesnika s AML u remisiji bolesti s vrijednostima kontrolne skupine. U skupini bolesnika bilo je 12 bolesnika s AML. Kontrolnu skupinu čine 16 ne-hematoloških bolesnika. Dijagnoza bolesti postavljena je nakon citomorfološke i citokemijske analize koštane srži i periferne krvi prema FAB-klasifikaciji i kriterijima Chesona i suradnika. Laktoferin je u stanicama granulopoeze određen APAAP imunocitokemijskom metodom. Rezultati usporedbe su pokazali da je, iako su bolesnici s AML bili u remisiji bolesti, postotak laktoferin pozitivnih stanica bio je puno manji (medijan 60.5, raspon 17-96) u usporedbi s laktoferin pozitivnim stanicama granulopoeze kontrolne skupine (medijan 95, raspon 83-100). Opažena razlika bila je i statistički značajna (p

From 1988. to 1998. a total of 40 patients with acute leukaemia (AL) presented with unusual blast immunophenotype. There were 12 females (30%) and 28 males (70%), aged 20-60 (median 41). The FAB types were ALL (10), ALL-L1 (4), undifferentiated AL (AUL, 18) and AML-M1 (8). The basic panel of reagents run on all patients included CD2, CD5, CD10,CD19, CD13,CD33, Cdw65, HLA-DR and CD34, followed by various second-line linegae-associated reagents. Cytogenetic abnormalities were found in 16 of 40 patients with unusual blast-immunophenotype. Match-pair analysis was conducted according to age, sex, FAB, cytogenetic abnormalities and number of WBC at diagnosis. Two control groups were established: AML (n=51) and ALL (n=26). Remission rate for patients with unusual blast marker expression was 48%, which was in contrast to AML (74%) and ALL (68%) (p

The results of marrow transplantation for AML is reported. Allotransplant is superior than autografting and chemotherapy for younger patients in 1st CR AML patients.

alogeneic and autologous stem cell transplantation

From 1987. until 1995. 110 patients with de novo acute leukaemia were included into prospective study. Median age was 34 years (15-60). The majority of patients have AML-M2 (41%) or AML-M1 subtype (23%) according to FAB. Thirteen (12%) patients have AML-M3 subtype. AML-M4 was observed in 13 patients (12%) and AML-M5 in 9 patients (8%).In five patients (4%) a diagnosis of AML-M6 was established. Cytogenetic abnormalities were found in 79 (72%) patients. Thirty (27%) patients were classified as a good prognostic group, 43 pts. (39%) as a poor prognostic group, and 37 (34%) as intermediate group. Complete remission was obtained in 81% of patients with good karyotype, in 65% patients with intermediate karyotype and in only 37% in poor prognostic group (p=0.001). Probability of relapse for patients with poor karyotype is 82%, for intermediate group 68% and for patients with good karyotype 56% (p=0.05). In multivariate analysis older patients with poor karyotype, with AML-M4 or AML-M5 subtype, low number of platelets and/or high number of WBC at diagnosis have high probability of induction treatment failure and low probability of disease free survival.

alogeneic transplants, acute leukemia

treatment of chronic myeloid leukemia with cord blood transplantion

To determine the impact of age on the outcome of bone marrow transplantation in patients with acute leukemia. 241 patients with acute leukemia who underwent transplantation of allogeneic (152 patients) or autologous (89 patients) bone marrow were included in the study. Allogeneic transplant was from an HLA-identical sibling. Cyclophosphamide followed by the total body irradiation or cyclophosphamide and busulfan were used in the conditioning regimen. Leukemia-free survival (LFS) was significantly better in younger patients compared to the older ones for all patients (LFS for younger patients was between 40-43% and for patients >45 years 27% ; p45 years ; p45 years 34% and 29%, respectively ; p45 years and 13-19% for younger age groups ; p45 years 31% (p

Biphenotype acute leukaemia is a very rare type of leukaemia characterized by the oresence of myeloid and lymphoid markers. In this paper we describe a patient with acute leukaemia (AL) consisting of two cell-populations, one expressing CD34, HLA-DR and cytoplasmic CD3, and the other expressing myeloid marker CD13 and cytoplasmic CD3. Cytochemical analysis revealed 10% MPO+ cells and 70% PAS+ cells. Cytogenetic showed 46xx, T(3 ; 7)(q21 ; q34-35). This unique finding is of special interest since 3q21 has been seen in AML patients with abnormal platelets while 7q34-35 has been associated with TCR locus and associated with ALL.

The aim of this study was to asses the contribution of the comparison between immunocytochemical positivity of blasts for myeloperoxidase and CD34 marker to higher accuracy of differentiating morphologically undifferentiated AML from acute lymphoblastic leukemias (ALL).

Seven patients with acute promyelocytic leukemia (APL)treated with all-trans retinoic acid (ATRA) for remission (CR) induction and with chemotherapy (CT) for consolidation of CR underwent residual disease monitoring through reverse transcription polymerase chain reaction (PCR) for PML/retinoic acid receptor alpha (PML/RAR alpha) fusion transcript. In six patients PCR was positive immediately after ATRA induced CR and/or after the first CT course.Two patients became PCR negative following repeated courses of CT and they are in remission 7 and 14 months, respectively. Four other patients relapsed. This pilot study indicates that PCR for PML/RAR alpha is very sensitive assay for detection of residual disease in APL.

The usefulness of a panel of monoclonal antibodies against leucocyte surface antigens - Tll/CD2, Tl/CD5, B4/CD19, B1/CD20, CALLA/CD 10, My9/CD33 and Ia/DR - was assessed in routine classification in the diagnosis of leukaemia. Eighty leukaemic patients aged >15 yr were divided into two groups: 56 selected patients diagnosed before immunological typing, and 24 patients with provisional diagnosis of acute leukaemia. The panel used delineated the blast origin in the majority of patients and selected those requiring further testing in a specialized center.