MDS in children

MDS in Children

LEkE&i Research

Pergamon

Leukemia

Research 23 (1999) S5 l-S54

134 EPIDEMIOLOGY Hennk

OF CHILDHOOD

MYELODYSPLASTIC

SYNDROME

Hale

Department

of Pediatrics,

Classification

Aarhus

University

Hospital

Skejby.

Denmark.

The FAB classification

has become widely accepted for MDS I” adults whereas the classification of childhood MDS has remaned rather controversial and mconststent. The m”st confltctmg area m the classification of childhood MDS has been the pediatric equivalent of what 11w FAB group termed CMML These children have m”st often been chrontc myeloid leukemia (JCML) it1 the British referred 1” as JUVenlk and Amertcan hterature. whereas others have favored the FAB term CMML There is an mternational consensus that the different terminology does not reflect different disorders and the term juvenile myelomonocytic leukemta (JMML) has been proposed and has attamed mternattonal acceptance. Children with MDS and -7 have often been considered a distinct hematologtc dtsorder described as the tnonosomy 7 syndrome. Huwever. loss of chromosome 7 occurs in a heterogeneous group of myeloid disorders and there are no data to support the concept of nionosomy 7 as a dtstinct syndrome. It is recommended to use the FAB classlficatlon to chtldren with the modification that up t” 20% blasts m pertpheral blood IS accepted in JMML. Incidence. Despite an increasing number of reports on childhood MDS llttle IS known about the epidemiology. The reported proportion of MDS of all leuhemlas has vatied from I % t” 16% Estimating the frequency of MD!? from series of AML underestimates the true incidence because .&ML. does not develop m all cases of MDS and some children dx from c
Two studies from Denmark and British Columbia, Canada, have reported population based data. The tw” studies identified 77 children with MDS representing 7% of all hematologic mahgnancies in children currrsponding t” an annual incidencr of 3.6imillion (Table). Table. Incidence of leukemia in childret! 0 14 years Data from Denmark 1980-1991 and British Columbia 1982-1996 % MDS AML

7 12

MPD ALL Total

A 79 100

CML

incidence/lOb 3.6 5.7 0.6 3:.‘6 48.7

MDS has been diagnosed more frequently m children in recent years due t” an mcreased awareness of the dtsease, but there are no evtdence t” support an increasing incidence with time. Age and FAB group distribution. The medtan age at presentation is 2-3 years wth a peak mcidence in the youngest children, mostly due to the occurrence of JMML m infants and young children (median age I3 months) RAE9 and JMML each accounts for one third of the patients, RA a( diagnosed in 20% and RAEB-T in 15% It 1s noteworthy that RARS. which constxutes about 25 % of all adult cases is almost nonexlstmg in children. I’redisposing conditions are found m approximately one third of the cases. compared with less than 10% of the AML patients Familial MDS Famtlial “ccurrence of MDS has been reported in a number of cases. Many of the famdial Casey have been associated wth mot~osom~ 7 Familial MDS has been claimed to acc”unt for as many as one third of all children with MDS, but commuted only a few prrrmtages in larger series Constitutional cytogenetic abnormalities. Down syndrome IS the m”st frequently encountered predisposing condition occurrmg in 20.30% of lh”sr wth RA. RAEB or RAEB-T. Children with Down syndrome have

0 145-2 126/99/$-see front matter 0 1999 Published PII: SO145-2126(99)00065-X

by Elsevier

during the neonatal period an increased rtsk of transient abnormal myelopoiesis and during early childhood an increased risk of acute leukemia, ALL as well as AML. MDS in children with Down syndrome IS frequently associated with isolated thrombocytopenia as the presenting feature and trisomy 8 as the most comm”” acquired cytogenetic abnormality. MDS in Down syndrome occurs virtually always during the first four years of hfe. Chtldren wtth Down syndrome have a very favorable prognoses when treated mtensively Thus, there are many dlstmctive features indicatmg biologic differences between MDSIAMLM7 m children with and without Down syndrome.. This type of MDYAML may be unique t” children with Down syndrome. Hematologic malignancies, predominantly MDS. have been reported I” a few patients with constitutional trisomy 8 mosaicxm. Klinefelter syndrome and Turner syndrome have been reported m ass”ctatt”n wth MDS. but large cohort studies have failed to confirm the association Fanconi anemia. Patients with Fanconi anemia most often present wth pancytopenia and a hypocellulat bone marrow. A few patxntr prrsrnt with MDS or AML MDS may be the presentmg feature of Fanconi anemia as late as m the fourth decade. Recent data suggest that as many as SO % of those with Fanconi anerma develop AML or MDS before the age of 40 years. Fancom anerma has predommantly been associated wttb RA and RAEB Aplastic anemia and congenital neutropenia MDS develops in a signif[cant number of patienta with aplabtic anemia not treated wth BMT Aplastlc anemta has been considered as a preleukemx disorder MDS does not develop in those treated with BMT makmg it !m”re hkely that aplast~c anemia represents a predlsposmg condltlon for the development of MDS. but not an established early MDS Progresslo” to myclotd malignancies has been documented I” congemtal neutropenia. Especially MDS associated wth mnnoqomy 7 has been reported. Before tlx introduction of G-CSF mob1 patxnts with congaural neutropenia died I” early childhood and it 1s still uncertain whether the risk of MDS is hrgher than prior to the era of G-CSF treatment Recent data suggest tint the combmatton of cyclosporine and G CSF lead to a higher risk of MDS or AML I” pattents wth aplastic anrm,a

Neurofibmmatosis type 1 (NFI) has been reported in a large number of clnldrcn with JMML Most of the patients have been boys below fwe years of age. Juvende xanthogranulomas may be an associated feature NFI IS diagnosed in 10.15% of the chtldren wtth JMML Due to the paucity of symptoms of NFl I” mfancy the dlagnosls may easily bc overlooked and NFl mutatt”ns have been demonstrated in another 10% of JMML patients without a clm~cal diagnosis of NFt The molecular tnechantsm underlymg the increased risk of JMMI IF related t” thr mutated NFI gene codmg for ncurotibromw which modulates the Ras prorem Lack of neurofibromin leads t” a penwent actlvatmn of the Ras prorem and hence dlsturbed signal transduction in the cells as If the ras gene had been mutated AML and MDS subtypes other than JMML have only “ccastonally been reported I” chtldren with NFI Previous cbcmotherapy The USC of chemotherapy may cause tberapyrelated MDS. The risk is slgmftcantly increased tw” tn ten yrars after the treatment for the primxy mahgnant disease and peakr 4 I” 5 years fnllowinp the leukemoeenic theraov There seems to be tw” different type” of therapy-related MDS. One is related to treatment wth alkylatmg agents resulting in MDS which cytogenetlcally shows deletions or loss of whole chromosomes. The other type IS assoaated wtb the use ot eplpodophyllotoxms and acquired translocatlons ~nvolvmg chromosome band Ilq23 Environmental facton. The possible ctiologlc role of environmental tactors m childhood MDS IS vtrtually unknown The powble influence of exposure t” pesticides Ins been discussed i” childrm and young adults Other occupational factors. includmg radiation, may be implicated I” adults with MDS. but there are no valtd data on the role of exogenous factors ,n cluldhood MDS

.,

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MDS in Children 135

137

PROPOSALS OF TBS BWOG-MDS PATBOLOGY BOABD PORTBB EVALUATION OF DYSPLASTIC FINDINGS ON BONE HAKBOW ASPIKATES.

CHILDHOOD MYELODYSPLASTIC SYNDROME IN JAPAN: A RETROSPECTWE ANALYSIS OF NATIONWIDE SURVEY.

A. Cant&-Rajnoldi. I. Baumann. S. Benu, G. Kerndmp and E. van Wering (BWOG-MDS Pathology Board). Laboratorio di Bicerche Cliniche. ICP,Milano,Institut fur Pathologic der Universitat. ErlanSen; Cattedra di Bmatologia. Universitl di Bona; Institute of Pathology. Odense Dniversity; DCLSG, Tbe Hague. Diagnosis of myelodysplastic syndromes depends mainly on the evaluation of bone marrow cytology and could then be hampered by subjective criteria. With the aim to find more objeciive and reproducible parameters, the members of the EWOG-MDS Patholoev Board have been involved in the last years in the preparation of a new form for the evaluation of dysplastic features on BH aspira tes. On the basis of previous experience, cytological parameters of the three hemopoietic lineages were selected and a scoring system proposed to measure the degree of dysplasia which takes into account the percentage of cells carrying a given abnormality.Selected parameters in the erythroid series are: megaloblastoid changes, lobulation and cytoplasmic multinuclearity, nuclear granules or inclusion; in the myeloid series: bizzarre nuclear shape, hypo or agranularity, nuclear-cytoplasmic asynchrony and Pelger anomaly; in the megakaryocytic lineage: micromegakaryocytes, small binucleated megakaryocytes, cells with small round separated nuclei and megathrombocytes. A series of BM smears have been circulated blindly among the members of the board on successive occasions and the results were discussed by the whole panel of pathologists at different meetings. Analysis of the main discrepancies among the observers allowed a progressive improvement of the reproducibility. A more extensive analysis of this proposed dysplasia scoring system will be possible in the context of the EWOG-MDS 98 Prospective Study of the diagnosis and treatment of MDS in childhood.

136

Childhood myelodysplastic syndrome (MDS) is a rare disease and the prognosis is generally dismal. Development of a treatment strategy based on the data from a large number of patients is needed. In 1997, the childhood MIX committee was established in Japan and a retrospective analysis was conducted in a nationwide fashion. The patients with MDS under the age of 16 were enrolled. Diagnosis was made between 1990 and 1997 based on the FAB classification. The data from approximately 60% of all the institutes in Japan were available for this preliminary analysis. Totally 204 children were registered. In the same time period, hematologic malignancy was diaenosed in 1.697 children at the same institutes. MDS constituted 7.8% of all le;kcmias and 30.9% of acute myelogenous leukemia. Primary MIX was diagnosed in 129 patients: RA 23, RARS 1, RAEB 16, RAEBT 24, CMMoL 11, JCML 41 and unclassified diseases 13. Constitutional abnormalities were identified in 27 patients: Down syndrome 14, Fanconi anemia 8, other disorders 5. Secondary MDS following non-constitutional diseases was diagnosed in 48 patients: aplastic anemia (AA) 20, malignancy 23, other diseases 5. Overall survival (OS) at 4 years for primary MDS was 46+6%: 61+8% for patients treated with bone marrow transplantation (Bm and 28+7% for those treated without BMT (p=O.OOl). Regarding the similarity of hematological findings, CMMoL and JCML were reclassified as a single entity of JMML as proposed by others. OS for JMML was 35+9%: 56rt15% for the patients treated with BMT and 16_t8% for those treated without BMT (p=O.OOl). OS for non-constitutional secondary MDS was 36+8%: 4Oi12% for cases after AA and 33+11% for the cases after malignancy. Further analysis of the data is currently undertaken to identify the risk factors and to establish treatment modalities.

138

INTERNATIONAL MYELODYSPLASTIC H. Haslc.

A., A. Ohara, S. Kojima, M. Tsuchida, Y. Hayashi, K. Ikuta, J. Okamura, K. Koike, E. Ishii, Y. Komada, S. Hibi, H. Sasaki, I. Tsukimoto, T. Nakahata for the MDS committee of Japanese Society of Pediatric Hematology, Japan.

PROGNOSTIC SYNDROME

G. Kcrndrup.

L.D.

SCORING SYSTEM IN CHILDREN

Wadswirrth.

FOR

K R Schultz.

Department of Pediatrics. Aarhus Un~vers~tv Hoso~tal. Department of Patholow. Ddense Lhverwy Hosp~fal, Denmark, Department of Pathology and Pedlatrlcs, CMdren’s and Women’s Health Center of Br,t,sh Columtx. “ancouver, Canada. The International Prognostic Scoring System (IPSS) Rw MDS was generated on tlx basis of studies on MDS in adults. The IPSS weighted data on hone marrw (BM) hlasts count, cytilprnia and cytogcnetics and separated patients into four prognostic _eroups: Low, intermediateI (INTI b. intrrmediatc-2 (INTZ) and High. The IPSS has not yet hem evaluated m children We combined data from two population hascd studies including 77 children diagnosed in Denmark 1980-1991 and in British Columbia. Canada 1982-I 996. The present study is hased upon the 70 children with cytogcnetic data. The morphologic diagnoses were RA. 15. RAEB: 23, RAEB-T. 9. JMML 23. Using the IPSS criteria the patents were grouped accordin_e to Cympenia O/I (n=25), 2/3 (n=45): Karyotype Good (t1=29). Intermediate (II= 17). Poor (n=24): BM blasts ~5% (n=26), 5-10% (n=25), 11.20% (n=l4), 21.30% (n=4), resulting m thr fr~llowing risk groups law (n=3), INTI (n=34), INT2 (n=20). and High (n= 13). Survival was used as end-point. The risk of progression to AML could not heen evaluated since mat patienrs were treated h&ore progression. Overall survival was 33 %. 5.yrar survival in the prognostic groups was Cytopenia Oil: 30%. 213: 35%; Katyotype Gotxi: 42%. Intermediate: 35%, Poor: 25%; BM blasts <5%’ 50%. 5.10%: 22%. IO30%: 26%. The 5.year survival showed no si_gnificant relation with IPSS risk group: Low: 33%, INTI: 48%, INT2: l6%, and High: 25%. A strot,_eer relatiot~ was ohserved by FAB group; RA: 73%, RAEB: 34%. RAEB-T: 22%. JMML: I I %. Survival was 53% in those who received BMT vs 24% in those who did not receive BMT. No major changes in the prognostic factors were ohserved restricting the study to patirns who did not receive BMT. The IPSS seems to provide lrss prognostic informalon in children than in adults, reflecting differences in frequency of cytogenetic ahnormalities and response to therapy between children and adults. More studies are needed for evaluating the prognostic factors in childhood MDS.

CLINICAL, CYTOLOGIC, AND CYTOGENETIC ANALYSIS OF TWELVE CASES OF MYELODYSPLASTIC SYNDROMES IN CHlLDNOOD JM Souza,ICBSantcs,MLMSilva, C Bcquinpani,AC0 Rccha,AP Leite. Fv Simdas,ESFWAbdelhay.lnstitutoEstadualde tiematologia‘Arthur de Siueira Cavalcantt’and Instttutode Biifisica ‘Cartes Chagas Filho” da UniversidadeFederaldo Rio de Janeiro.Rii de Janeiro,Brazil MyelcdysptasticSyndromes(MDS)in childhoodare rare and accountfcr lsss then 10% of all hematolcgicmalignancies.We studiedthe clmical: cytological, and cylcgenetic features of 12 cases of primary MDS in childhooddiagnosedbetweenDecernter 1992and November1998.The age ranged from five mcnths to 14 years (median: 19 months);eight patients were boys. Hepatomegatyand splencmegatywere found in seven cases. At the diagnosis variabte degree of anemia and thmrnbwytopeniawere seen. The WBCrangefrom 19X to 137x lDs/L All pattentsccuki be ctassii accmdingto the FABsystem:five had RA, four CMML, one RAEB,one RAEBt,and other one MRS. Hypcplastic MDS was seen in twc patients. Karyotype was availabte fcr all the pagentsandshowed donal qtcgen& abnormalitiesin seven cases. fdOn0Smyor tradmltts of 7 were found in four patkmts. Other abnormatkieswere: -8, del 29q, and del 12~. Five patientsdied, four of whom due to sepsis. Three patients developed acute leukemia. The mediansurvivaltime was eightmonths.

MDS in Children

s53

139

141

REFRACTORY ANEMIA IN CHILDHOOD &&t&s, I Baumann, S Fenu, J Harbott, H Hasle, G Kemdrup, G Mann, CM Niemeyer, T Rogge, A Schmitt-Griiff, L Sianati, R Slater, J Stary, E Van Wering, M Zimmermann. European Working Group of MDS in Childhood (EWOG-MDS). I&z&&n: Refractory anemia (RA) has been extensively studied in adults, but has not been reviewed in larger series of children. Patients The data of 36 children (cl8 yrs) with RA (n=34) and RARS (n=2) were retrospectively analyzed. Median age at diagnosis was 8.4 years (range l-17 y’s), There were 20 boys and 16 girls. &.,QI& Bleeding and malaise were the presenting sings in about half of the children. At diagnosis 95% had anemia, 83% thrombopenia and 66% leucopenia, while 46% presented with trilineage cytopenia. Hypo- or normocellular bone marrow was found in SO%, dysplasia of the erytbroid series was common. Cytogenetic abnormalities were seen in 26/34 patients, monosomy 7 in 16, trisomy 8 in 3 and in 6 complex aberrations were found. Thirteen children didn’t receive any therapy and had no progression; 9 of those are still alive with a median observation time of 0.9 year Progression was seen in 16 with a median time of 1.2 years to progression. All children (n=5) with ANLL-type therapy and no stem cell transplantation (SCT) died SCT was done in 20 children: n=14 with RA (8 in CR), n=6 in other forms of MDS/ANLL (2 in CR). Two children, both with monosomy 7, had a relapse after SCT, while transplant related mortality was the cause of death in 8 patients. With a median observation time of 5.6 years, event-free survival after SCT was 43+/- 12% at 5 years, The overall 5 years survival was 27+/- 13% Conclusion: RA in children has distinct clinical, hematological and morphological features Clonal chromosomal aberrations are common. RA in childhood has a high progression rate and time to progression is short Survival was found to be low, SCT early in the course of the disease seemsto be the treatment of choice.

EVALUATION OF 40 CHILDREN WITH MYELODYSPLASTIC SYNDROME IN TURKEY G.HicsiTmnez,M.Cetin, LYenicesu, A.Koq, M.A Tuncer, D. Aktaa, E.Tun$bilek. Hacettepe University, ihsan dogramaci Children’s Hospital, ANKARA, TURKEY Between 1991 and 1999,40 children (20 male, 20 female) with a median age of 4 years (ranged from 4 months to 16 years) were seen in our institution. Fifteen children presented with CMML, 13 with RAEB, 8 with RAEB-t, one with RA with sideroblastosis and 3 with JMML. At diagnosis thirteen (32.5 %) children had extramedullary infiltration (EMI, orbitaocular, gingival, pleural pericardial, spinal, pyodetma gangrenosum, relapsing polychondritis). Cytogenetic abnormalities were noted in 10 (33%) of 30 children studied. Five patients had coexistent constitutional abnormalities (Bloom syndrome, Fanconi’s anemia, Down syndrome, Ataxi telengiectasia and Neurofibromatosis). Treatment was initiated with high-dose methylprednisolone (HDMP,20-30 magiday, p.o, in a single dose) which can induce differentiation and apoptosis of myeloid leukemic cells in viva and in vitro. Cytotoxic chemotherapy was added to HDMP four days after initiation of treatment. Twentyfive patients have received therapy and evaluable. Nineteen children (76%) achieved complete remission, 3 had PR (12%). Dramatic decrease in the size of EM1 have been noted in all patients few days after initiation of HDMP alone. BMT could be performed in 5 patients. Four were alive for 2.5 to 10 months, Five patients who received chemotherapy are still in remission 4 and 8 years (4 with CMML and pleural effusion). Three patients (RAEB,RAEB-t) progressed into AML 3, 8 and 13 months after remission. The remaining 6 patients are alive between 4 months to 3 1 months. Further stud,es are needed to explore the advantage of the addition of HDMP to cytotoxic drugs in children with MD8

140

142

CHILDHOOD MYELODYSPLASTIC SMDROME IN THE BRAZILIAN COOPERATIVE MDS STUDY GROUP

TURKISH NATIONAL PEDlATRIC SYNDROME REGISTRY

Aguiar BS, Alencar DMS, Andrade MP, Campanaro CM, Cameiro J. Lee ML, Loggetto SR, Lopes LF, Machado TMS, Pita MT, Soares FA, Toledo SC, Tone LG, TorreCD,Valera E,Velloso ERP Luil

Femandu

Lopes Chairman-

GCB-SMD

e-mail

Iflopes ‘a; opus.com.br

In the last 5 years the GCB-SMD has been the reference for the brazilian pediatricians concerning this patology We present the 36 patients that were registred in this period coming from 9 different centers.8 from Sao Paul0 State and one from Bahia FAB classification was used. 5 children were RA, 1 RARS, 10 RAEB, 4 RAEB-t. 6 LMMC and 10 cases did not fit the FAB criteria Initial complaints were anemia 16 (45%), bleeding in 8 (23%) and pallor in 5 (14%). Cytogenetic abnormalities were found in 7118 patients 46,XY,br , 45,Xx,-7 ; 46,XY,del 4 ; 46,XX,br, 46,XY del ISq-,del22q- ,46, XY,br ; 46,XY,+ 21, 46,XX,tr(9;22) ; 6118 are waiting the results and 5 are normal The bone marrow was hipocellular in 12 children. The transformation into acute leukemia occurred in 1I Eight were AML: 3 RAEB, 3 RAEB-t, 1 LMMC, I non FAB, in 2 AML Ml, 2 M4, 2 M6 and 2 non FAB classified. Three transformed into ALL 2 RAEB and 1 RA. Supportive treatment was given to 15 patients, 8 were treated with AML protocol. 3 as ALL, 1 with BMT, 5 as CMML, and 1 received chemotherapy outside a protocol Two died before treatment was begun From the 5 RA, 2 are alive, 2 died and one are lost, the RARS patient are alive, from 10 RAEB 4 are alive and 6 died from 4 RAEB-t all died, from the 5 CMML 4 died and one is lost, and from the IO non FAB-MDS 5 are alive (one post BMT), 3 died and one is lost

MYELODYSPLASTIC

M.Cetin, G.Hi@jnmez, M.A Tuncer, N.Cetingtil, K.Kavakh, C. Vergin, A.Yegilipek, E.Duran, T.Patuoglu, G.irken. Ilacettepe University, Ege University, Dr Behget Uz Children’s Hospital, Akdeniz University, Karadeniz University, Erciyes University, 9 Eyliil University -TURKEY Between January 1979 to January 1999,98 patients under the age of 16 years with primary MDS as defined by the FAB diagnostic criteria were seen at seven pediatric hematology centres in Turkey. The patient group consisted of 56 males and 42 females with a median age of 6 years (0.2-16 years). Morphological assessmentof the peripheral blood and the bone marrow showed that 14 patients had refractory anemia @A), 2 patients RA with ring sideroblastosis (RARS), 42 patients RA with excess of blasts (RAEB) , 16 patients RAEB in transformation (RAEB-t), 3 with juvenile myelomonocytic leukemia (JMML) and 21 patients were diagnosed as chronic myelomonocytic leukemia (CMML). The overall mean survival was 14.8 months (0.5-86 months).

MDS in Children 143

145

RESULTS OF MYELODYSPLASTIC THERAPY IN CHILDREN. REPORT CHILDREN’S LEUKEMIA /LYMPHOMA A.Chybicka’,

P.K&cki

J.Armata*,

A.Eliasiriska*,

M.Matysiak5,

4,W.Pietras1,

J.Bogustawska-Jawonka’,D.W6jcik’,

J.Kowalczyk3,

A.Krauze5,

SYNDROM (MDS) OF THE POLISH STUDY GROUP. T.Jackowsk&,

K Stefaixka4,

Cracow* Poland.

of Children’s

Lublin3,

Hematology

and Oncology, WrocIawI,

Poznan4 , Warsaw536 Universities

of Medicine,

Prognosis of most children with MDS is poor and there is no consensus in the optimal treatment strategy. Fourty children 22 boys and I8 girls aged from 6 mth to 17 years with MDS treated i period 1975-1998 y were included to the study. All cases of MDS were classified according to FAB modified classification. In 16 from 40 (40%) children RAEB-T, in 12 from 40 (30%) RAEB, in 2 from 40 (5%) CMML and in IO from 40 (25%) RA were diagnosed. The children were initially treated with Roacutan (12 children), ATRA (I child), low dosis of Ara-C (7 children), 6MP +VP 16 (2 children), corticosteroids-(4 children), GM-CSF (2 children) and 2 CDA (I child) with short period of improvement. In 9 children only supportive therapy was applied. In 22 from 40 (55%) children blastic transformation occurred in 14 from 22 (63,64 %) children AML-type and in 8 from 22 (36.36%) ALL-type). The children were treated according to BFM ALL and BFM AML protocols. In six children allogeneic BMT was performed. Two from five children died after BMT. One of them because of BMT related complication and one because of disease relapse. Four children alive 6-72 mths after BMT. EFS in 36 mth of observation is 0.29. Our and literature data showed that allogeneic stem cell transplantation (SCT) seems to be the therapy of choice. For patients lacking an HLA - identical family donor, SCT from unrelated volunteer donor is recommended.

144 RETROSPECTIVE liu

CHILDRF%

~cwmiic-Research

ANALYSIS WITH

OF’ HEREDITARY

T.Patlmglu, Z,GGndiiz,T.E.Pat~ro&M.A.br,R.X&sel Erciyes Unlversty Schcol of Eledicine, Rayseri-Turkey

K.Klus2,

R.Rokicka-Milewsk&,

H.WiSnlewska&sarz3

Department’s

ANExEwJiYF&soIDE0Y~~c-PAnrNAND Mv3mY!3PIAsrlC .c3mmmE

DISEASES

blvlDS

Insmute of Heredtrarv Pathology. Lvw.

Ukrame

Myelodyspiastlc syndromes (MDS) are rare m chddhood We reviewed rerrospectwel\ the climcal .md laboratory data ,~valinblc ior all palxnts reffered durmg lYY1 - IYYX ahlth dugnosed MDS or chronic myelomonocytic leukemia. 21 ~.IIICIUS wcrr clawtied according 10 the FAR classification as ~clrcc~or~ mcma (RA. n=(~). RA with excess of blasts (RAEB n=J) RAEB m translormatmn (RAEB-t: n=i) and chronic ~mvcmmonocvllc leukemld (CMML, n=l,) -\mony 31 children were h girls and I3 boys from 5 months to 14 yc~s (the median age ar the time of diagnosis was 4.4 yrs). In 8 pac~nts (3X.I”0) MDS was diagnosed to I year. A girl of 14 yrs wllh Y-years history of leukopenia and splenomega!ia diagnosed R.-\EB-1; at’~er that transformed AML F.4B-M7. Some of these patients (4121. lY.O”,) have combination of MDS wth various constitutional disordssrs: Down’s syndrome (47, x.x+21, 340), phenilketonuria. birth defect of kidney. mlcrocephalia. In the case one girl, I4 yrs with MDS (RA) and tuberculosis of lungs, mother died from leukemia In this girl in I I months were diagnosed splenomegalia and leukopcnia. In one boy, 4 yrs with MDS (RA) and birth defect of kidney dystopia, mother had 3 spontaneus abortus. In 5 (33,3”0) patients from IS wilh R4DS acre diagnosed chromosomal abnormality, ITlOSt comma?-polyploidia. Monosomy 7 was diagnosed in boy, Y yrs with CM&IL. In one patient wwc marked prcsencc at the same lime S-X mutant cIo!~cs wth different quantity chromosome and structure changes. WC observed a great frcquence hereditary disease hy small number ofpatients. Our study to be continued.

We described a case of glmerulopabty and peristent leulapenia and thrabcqtopenia in an eleven years patient was adimitted Peripheral baxl myeloblasts (10%) were He was diagmsed as a C3,C4 and imwmglobulins

anenia, old boy ‘Ihe

for urara, pancytqenia and hepatosplenaregaly. disclosed tisocytosis, poikilccytosis and detected in hypoplastic bone nwrrcw srrear. refracter an&a with excess blasts (RAEB). wzre nomal,antimclear antibody and

Hbs Ag were nigative. Light microscopy of the renal biopsy shoed chronic glanzrulopathy. Inmmchistochaical staining revealed IgA, IgC ad C3 depositon in the glareruli. l?espite of high dose aethyl prednisolcme therapy acute qeloblastic leukania was developed and subsequently low dose therapy conisist of damomycin, dexaethascme, thioguanine, vincristne, 5-azacytidin, cytoxan was administrated for four cure but he had no renission. Ihe patient has been fallowed

with

supportive

therapy

for

two years.