Haematologica. Journal of Hematology ABSTRACTS. 37th Congress of the Italian Society of Hematology. volume 84, suppl. to number 9, September 1999

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1 Haematologica established in 1920 editor-in-chief: Edoardo Ascari ISSN Journal of Hematology volume 84, suppl. to number 9, September 1999 Official Organ of the Italian Society of Hematology the Italian Society of Experimental Hematology the Spanish Association of Hematology and Hemotherapy the Italian Association of Pediatric Hematology Oncology 37th Congress of the Italian Society of Hematology September 26-29, 1999 Centro Congressi Lingotto Turin, Italy ABSTRACTS Owned and published by the Ferrata Storti Foundation, Pavia, Italy Mensile Sped. Abb. Post. 45% art. 2, comma 20B, Legge 662/96 - Filiale di Pavia Il mittente chiede la restituzione dei fascicoli non consegnati impegnandosi a pagare le tasse dovute

2 Poster

3 37 th Congress of the Italian Society of Hematology 71 APLASTIC ANEMIA AND ACUTE LUKEMIA P001 MDR1 IS A POOR PROGNOSTIC FACTOR IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS UNIFORMLY TREATED ACCORDING TO GIMEMA 0496 PROTOCOL A. TAFURI ON BEHALF OF THE GIMEMA COOPERATIVE STUDY GROUP Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma Cellular drug resistance is one of the reasons of treatment failure in acute leukemia. Overexpression of the multidrug resistance gene (MDR1) and its protein (Pgp) has been frequently correlated with poor prognosis in acute myeloid leukemia (AML), particularly in elderly patients. In contrast, less information is available on the role of MDR in acute lymphoblastic leukemia (ALL), especially in adult cases. Aim of our study was to evaluate the incidence and prognostic value of the MDR1 protein, as well as its functional expression, in newly diagnosed adult ALL patients uniformly treated according to the GIMEMA 0496 protocol. In 222 cases, we measured by two flow cytometric tests the P-gp expression (MRK16) and the Rhodamine 123 (Rhd123-E) functional dye/ drug efflux with/without the MDR1 modulator Verapamil. The results were analyzed using the Kolmogorov-Smirnov statistic method (D-value) and the mean fluorescence index (MFI). P-gp expression ranged between 0 and 0.77 with a D-value > 0.01 (MDR+) in 26% of cases (58/222). Analysis of the 138 patients so far evaluated showed a significantly (p=0.003) higher frequency (81%) of MDR- patients (P-gp) who achieved a complete remission (CR) compared to MDR+ patients (53%). A significantly (p=0.03) higher frequency (65%) of relapse was recorded in the group of MDR+ patients. Moreover, a significant (p=0.002) difference in the median (m) event-free survival (EFS) was found between P-gp positive and negative patients: 5.5 vs 12 months, respectively. In addition, detection of the functional dye/drug efflux showed a Rhd 123-E ranging between 0.38 and 3.66, with a value > 1.10 (MDR+) in 14% (23/167) of patients. A significant (p=0.009) difference in CR achievement was also observed between efflux negative and positive patients (80% vs 50%). These results show that MDR1 is overexpressed in only a quarter of adult ALL patients; however, these cases are characterized by a lower likelihood of achieving CR, a higher incidence of relapse and a shorter EFS duration. The poor prognostic impact of MDR1 overexpression so far recorded in the ongoing GIMEMA 0496 protocol, suggests the possible use of MDR1 modulator agents in a proportion of adult ALL patients. P002 FLUDARABINE AND HIGH DOSE OF CYTOSINE ARABINOSIDE FOR THE TREATMENT OF REFRACTORY ACUTE LEUKEMIA OF CHILDHOOD S. CHIARETTI, M.L. MOLETI, R. BATTISTINI, S. BERNASCONI, F. GIONA, A.P. IORI, A. PESSION, R. RONDELLI, A.M. TESTI, F. MANDELLI Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma; Clinica Pediatrica, Università di Bologna Fludarabine (FLUDA) and high dose Cytosine-arabinoside (HD-ARA-C) associated or not of granulocyte stimulating factor (G- CSF) have been utilized for treatment of poor prognosis acute leukemias, showing efficacy and feasibility in adults. These results prompted to employ this schedule also in pediatric patients. At University of Rome and Bologna, FLUDA (30mg/sm/day for 5 days) associated with HD-ARA-C (2 gr/sm/ day for 5 days) with or without G-CSF (from day 1 to PMN recovery ) (FLA or FLAG schema), was used to treat children with advanced acute leukemia. Twenty-nine children were enrolled: 19 were male and 10 female, with a median age of 8 ys (range2-17); 17 had a diagnosis of acute lymphoblastic leukemia (1 first early relapse, 2 first resistant relapse, 13 second relapse, 1 third relapse), 12 of acute myeloid leukemia (3 first early relapse, 1 first resistant relapse, 1 second relapse, 1 third relapse, 6 primary resistant). Sixteen received G-CSF. In 3 children with an available bone marrow donor, chemotherapy was administered in order to obtain bone marrow aplasia, immediately

4 72 September 26-29, Torino-Lingotto, Italy followed by conditioning and BMT: 2 of them are in complete continuos remission at 26 and 41 months, and the other relapsed 9 months after transplantation. Twenty-six received protocol FLA/FLAG as salvage chemotherapy. In this group the response rate (CR+PR) was 58%: 12 (6 acute lymphoblastic leukemia, and 6 acute myeloid leukemia) obtained complete remission, 3 (1 acute lymphoblastic leukemia, 2 myeloid leukemia) achieved partial remission (M2 bone marrow) and 11 were resistant. Nine of the responders are alive and 6 died at median follow-up of 5 months (range 1-43 months). Myelosuppression was the major toxicity with a median time of neutropenia of 16 days (range 7-35), and thrombocytopenia of 18 days (range 11-29); 15 FUO and 11 sepsis occurred.; any other side effects were observed. In conclusion, in our experience protocol FLA/ FLAG resulted effective and feasible in heavily preatreated children with advanced acute leukemia. P003 DOSE-INTENSIVE THERAPY INCLUDING STEM-CELL TRANSPLANTATION IMPROVEs OUTCOME IN ADULT ACUTE LYMPHOID LEUKEMIA (ALL) G. DEL POETA, F.BUCCISANO, L.MAURILLO, A.VENDITTI, M.C.COX, A.TAMBURINI, L.MORINO, A.RICCITELLI, M.POSTORINO, M.I. DEL PRINCIPE, L.CUDILLO, B. DEL MORO, M.MASI AND S.AMADORI Dept. of Hematology, University Tor Vergata, Roma In an attempt to improve long-term disease-free survival (DFS) in ALL, from 1995 to 1998 we treated 21 adult patients with newly diagnosed ALL with a dose-intensive regimen. The induction phase consisted of cytarabine (H-Ara-C) 3 g/m2/d for 5 days and Mitoxantrone (H-MTZ) 80 mg/m2 as a single dose on day 1. This combination was repeated for consolidation at reduced doses (Ara-C 3g/m2/d for 3 days and MTZ 40mg/ m2 on day 1). Prednisone (40 mg/m2/d), triple intrathecal therapy and GM-CSF were also included. Up till now, 15 patients underwent autologous (10) or allogeneic (5) stem cell transplantation. To evaluate the efficacy of this new approach, we performed a historical comparison with a conventional program such as the LAL 0288 GIMEMA protocol used in 44 ALL patients from 1988 to 1994 at our Institution. No significant difference was found between these two patients groups with regard to median age, WBC count, FAB distribution, immunophenotype (B or T), cytogenetics (Ph1 chromosome), myeloid markers and P-glycoprotein expression. With regard to clinical outcome, number of early toxic deaths was found to be comparable among LAL 0288 cases and H-Ara-C/MTZ ones (8/ 44 and 3/21) as well as the rate of complete remission (CR) (88% v. 95.2%). On the contrary, the relapse rate was significantly higher among pts treated with the LAL 0288 (64.2% v. 22.2%; P=0.004). Moreover, overall survival and continuous CR (CCR) at 3 years were significantly longer in the dose-intensive treated pts (61% v. 22%; P=0.017 and 65% v. 27%; P=0.016, respectively). However, within poor risk ALL subset (15 Ph1+; 7 mature B-cell), no significant difference was noted with regard to CR achievement and relapse rate between the two regimens; a trend for a longer survival and CCR was found in Ph1+ H-Ara-C/MTZ pts (P=0.204 and =0.137, respectively). This dose-intensive approach assures rapidly high CR rates and longer DFS, even if long-term benefit appears to be restricted mainly to patients with standard risk ALL. P004 NEGATIVE PROGNOSTIC RELEVANCE OF CD45RA EXPRESSION IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA N. CASCAVILLA, G. D ARENA, L. MELILLO, M.M. GRECO, A.M. CARELLA, M.R. SAJEVA, R. MATERA, M. CAROTENUTO Department of Hematology, IRCCS, Casa Sollievo della Sofferenza Hospital - San Giovanni Rotondo The flow cytometric expression of 220 kd isoform of CD45 (CD45RA) antigen on 51 adult ALL (M 27, F 24; FAB L2 38, L1 13; Early Pre-B 6, Common 28, Pre-B 5, Early T 6, Late T 6; mean age 39.8 yrs., range 16-81) has been analysed. CD45RA has been positive > 20% on 32 cases (62.7%). The pattern of expression has been different among B and T lineage ALL: in B lineage ALL, no preferential relationship with the antigenic classes was identified; on the contrary, in T lineage ALL, it was expressed only on 4 early T ALL and completely lacked on late T ALL. With respect to negative

5 37 th Congress of the Italian Society of Hematology 73 cases, in the group expressing CD45RA a significantly higher incidence of L2 cytotype (84.4% vs 57.9%, p 0.039), B lineage ALL (87.5% vs 57.9%, p 0.02), MyAg+ ALL (50% vs 21%, p 0.037), CD34+ ALL (87.5% vs 63.1%, 0.046) and t(9;22) or BCR/ABL+ ALL (34.4% vs 21%, p NS) has been noted. In addition, in CD45RA+ ALL the mean age (43.3 yrs. vs 33.8, p 0.08), peripheral WBC count ( vs , p 0.06) and serum levels of LDH (1292 vs 729, p 0.08) were higher. In 16 cases flow cytometric analysis of CD95, bcl-2 and MRK16 has been performed: interestingly, an increased incidence of MDR phenotype has been observed in CD45RA+ ALL, however, the tendency to apoptosis was analogous in the 2 groups. All cases underwent GIMEMA protocols for ALL: 0183 in 6 cases; 0288 in 16 cases; 0394 in 7 cases; 0496 in 22 cases. C.R. has been achieved in 22 CD45RA+ ALL (68.7%) and 17 CD45RA- ALL (89.5%) (p 0.08). Independently from the protocol used, in B lineage ALL as well as in T lineage ALL a close relation between CD45RA positivity and lower response to therapy has been observed. In CD45RA+ ALL the O.S. median has been shorter than CD45RA- ALL (10 vs 25 months, p 0.024). Multivariate analysis (including CD45RA, CD34, MyAg, Ph, B/T lineage, age, sex, WBC, FAB) confirmed the negative influence of CD45RA on the survival (p , relative risk 6.8). In conclusion, our data demonstrate a negative clinical relevance of CD45RA expression on adult ALL. Larger studies are needed to confirm prognostic validity and to define the functional basis of this antigen. P005 ALL 0496 GIMEMA PROTOCOL: IMMUNOPHENOTYPIC CHARACTERIZATION IN 270 ALL PATIENTS AT DIAGNOSIS A.VITALE, ON BEHALF OF THE GIMEMA COOPERATIVE STUDY GROUP Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma As of October 1996 GIMEMA has activated the 0496 ALL therapeutic protocol for the treatment of adult acute lymphoblastic leukemia (ALL). Within this protocol, a centralization of a unified biological characterization carried out at diagnosis and during the clinical follow-up has been activated. The aim of the present interim analysis was to evaluate the immunophenotypic profile of a group of adult ALL patients enrolled in the same therapeutic protocol and to assess if the expression of myeloid antigen had a prognostic impact on the achievement of complete remission (CR) after induction therapy. So far, the immunophenotype of 270 patients is available: 217 patients had B-lineage ALL (80%) and 53 had T-lineage ALL (20%). Within B- progenitor ALL, the expression of at least one of the myeloid antigens CD13 and CD33 was found in 76 of 199 tested cases (38%), while CD34 positive expression was demonstrated in 172/213 cases (81%); the expression of CD117 was investigated in 30/217 cases and proved positive in 1/30 (3%). In T-ALL, the expression of at least one of the myeloid antigen was recorded in 11 of 47 tested cases (23%); such antigens were associated with a CD7 positivity in 11/11 (100%), while in only 4/11 (36%) was CD2 co-expressed. CD34 positivity was present in 14/50 (28%) of T-ALL; CD117 was found in 5 of the 13 tested cases (38%). This first analysis of an ongoing large multicenter study confirms that the presence of CD13 and/or CD33 associated antigens is less frequent in T-ALL compared with B-progenitor ALL (23% vs 38%) and that CD34 positivity is, as expected, higher in B-progenitor ALL compared with T-ALL (81% vs 28%). The results concerning the expression of the CD117 refer to an insufficient number of cases to allow any meaningful correlation. Of the 270 ALL patients analyzed at diagnosis, information regarding the achievement of CR after induction therapy is at moment available for 200 patients. No difference in the rate of CR was observed for myeloid antigen negative and myeloid antigen positive B-progenitor ALL (80% vs 72%); on the contrary, a significantly higher remission induction rate was observed in myeloid antigen negative T-ALL patients compared with myeloid antigen positive T-ALL patients (84% vs 43%, P=0.04). The complete data analysis referred to the immunophenotypic profile of the patients enrolled in the 0496 ALL GIMEMA protocol will be presented at the congress.

6 74 September 26-29, Torino-Lingotto, Italy P006 COMPLETE REMISSION (CR) IN ACUTE MYELOID LEUKEMIA (AML) WITH t(8;21) FOLLOWING TREATMENT WITH G-CSF: FLOW CYTOMETRYC ANALYSIS OF IN VIVO AND IN VITRO EFFECTS ON CELL MATURATION P. BOCCUNI 1, R. DI NOTO, G. MELE, A. VIOLA, C. RUSSO, S. COSTANTINI 1, A. DELLO RUSSO 1, C. LO PARDO 1, L. DEL VECCHIO 1, F. FERRARA Divisione di Ematologia and 1 Immunoematologia, Ospedale Cardarelli, Napoli G-CSF was employed as a tailored induction therapy in a 75 years patient affected by AML with t(8;21). One year before he had been diagnosed with prostate cancer extensively invading bladder. Bone marrow smear examination revealed 52% blast cell infiltration with frequent Auer rods. Patient s blast cells were CD34+, CD19+, a phenotype highly predictive of t(8;21); therefore, the patient was started on daily G-CSF at 450µcg/m 2. Few days later, cytogenetic examination confirmed t(8;21)(q22;q22). Following 14 days of G-CSF, CR was achieved after a progressive increase of WBC count along with appearance of myeloid maturing cells. Cell maturation and disappearance of blasts were confirmed by CD45-gating technique (CD45 vs side-scatter), modified by the introduction of a preliminary gating for nucleated cells with LDS Three months later, relapse occurred. The patient was restarted on G-CSF and achieved a second CR. While in second CR, the patients died from complications due to prostate carcinoma (massive urinary tract hemorrage). In order to compare the effects of G-CSF with other differentiation agents, bone marrow cells were cultured for 7 d in the presence of 0.5mM arsenic trioxide (As 2 O 3 ) or 0.5 µm all-trans retinoic acid (ATRA) or 60 ng/ml GM-CSF or 55 ng/ ml G-CSF. Control cultures without inducers were also established. In order to cytometrically quantify the maturing effect of inducers, we simultaneously analyzed CD11b and CD66b in a two-color assay. Gate was set on myeloid cells, excluding normal residual lymphocytes. No significant maturation was observed with As 2 O 3, ATRA and GM-CSF, while G-CSF promoted a marked shift towards mature cells. These findings were confirmed by morphological analysis of cytospins. At 7 days, BM samples treated with G-CSF showed 70 % maturing cells (neutrophils/bands), while controls, As 2 O 3, ATRA and GM-CSF treated samples showed 8%, 3%, 4% and 5% maturing myeloid cells, respectively. In conclusion, we showed that blast cells from t(8;21) AML undergo striking neutrophilic differentiation following in vivo and in vitro exposure to G-CSF, adding further clinical and experimental basis for the use of G-CSF in t(8;21) AML befire or concomitantly with chemotherapy. P007 EXTRAMEDULLARY RELAPSE IN A PATIENT WITH ACUTE LYMPHOBLASTIC LEUKAEMIA FOLLOWING ALLOGENEIC BONE MARROW TRANSPLANTATION S. IMPERA, F. INDELICATO, N. FILARDI, G.O. MANENTI, S. GANCI, G. GUIDO, C. SIMILI, G. MILONE, R. GIUSTOLISI Cattedra e Divisione di Ematologia con Trapianto - Catania Isolated extramedullary relapse in unusual sites, following allogeneic bone marrow transplantation (BMT) for adult Acute Lymphoblastic Leukemia (ALL), is a rare complication, associated with a poor prognosis. We present a case of an extramedullary relapse in the breast plus skin of a 29 year old women 7 months after BMT performed for a Ph-positive ALL in first complete remission. In april 1998, the patient, presented with bilateral breast masses and a 2cm cutaneous nodule on the scalp. Biopsy showed an ALL infiltrate on both sites. Immunohistochemestry showed positive stains in these cells by monoclonal anti- CD19, CD10, CD34; polymerase chain reaction (PCR) demonstrated BCR/abl trascript positivity. Bone marrow and cerebrospinal fluid were not involved and no BCR/abl trascript was detectable in these sites. Complete response of the breast and cutaneous masses was obtained with local irradiation ( 4600 cgy). The patient remains in complete remission 13 months after relapse. It can be speculated that allogenic BMT was effective in eradicating the initial clone but it was not in preventing the emergence of a new clone in extramedullary sites. The BCR/abl negativity in bone mar-

7 37 th Congress of the Italian Society of Hematology 75 row at diagnosis of an extramedullary relapse may be useful in predicting prognosis in these patients. P008 VERY RARE OCCURRENCE OF ILIOPSOAS HEMATOMA DURING ACUTE MYELOGENOUS LEUKEMIA (AML) G. MORANO, G.A. BRUNETTI, I. CARMOSINO, M. BRECCIA, S. MECAROCCI Department of Biotecnologie Cellulari ed Ematologia, University La Sapienza Rome Hematoma of iliopsoas muscle is a relatively common finding during some coagulopathies, tipically characterized by haemorrhages in the muscle-scheletric apparatus (haemophilias, anticoagulant drugs): it is seldom been observed during thrombocytopenia and never been reported during AML, in which are common parenchimal and cutaneous haemorrhages. We describe the occurrence of iliopsoas hematoma in a patients aged 62 years with RAEB t evolved in AML (October 97): due to age and previous myelodysplastic phase, he received supportive care and Hydroxyurea, with a good control of AML and excellent quality of life but persistent severe thrombocytemia (PLTS < 10 x 10 9 /l). On December 98, he presented a lumbosacral pain with irradiation to left leg; as he had referred a previous discal herniation, a lumbar Rx and TAC were performed, resulting both negative. The antalgic treatment with Paracetamole + oppioids achieved partial pain relief. On February 99, he was admitted to our Hematological Emergency Unit for a new increment of pain with irradiation to inguino-crural area and antalgic thigh flexion. Ecography and CT scan of inguino-crural area revealed an ovoidal disomogeneous mass (diameters 12.8 x 5.8 cm) in the context of iliopsoas muscle, consistent with a diagnosis of hematoma. There were no previous traumatic event as well as no local finding. Coagulative profile showed only a mild prolongation of PT-INR (1.34). As the patient was not eligible for a surgical drainage due to thrombocytopenia (PLTS 9 x 10 9 /l), he received daily PLTS concentrates, antifibrinolytic treatment, steroids and oppioids. After 10 days of treatment, he achieved a pain relief, with reduction of the mass (diameters 10.4 x 4.0 cm), and was discharged. Three weeks later, there was a new exacerbation of inguinocrural pain, concomitant with hyperleukocytosis: echography and CT scan showed an enlargement of hematoma (trasversal diameter 9.5 cm), with exstension to Scarpa triangle. The patient died on April 99 from disease progression. Our report outlines that a hematoma of iliopsoas muscle may rarely occur also in thrombocytopenic patients, without coagulopathies and/or other appreciable causes. P009 PRIMARY TESTICULAR GRANULOCYTIC SARCOMA: CASE REPORT C. FIORANI, G. VINCI, P. SPADAFORA, B. CASOLARI, M. COSENZA V. MEDICI, G. BONACORSI, * R. FELICINI, S. SACCHI Dipartimento di Scienze Mediche Oncologiche e Radiologiche. Università degli Studi di Modena e Reggio Emilia; *Dipartimento di Medicina Clinica e Sperimentale. Università degli Studi di Perugia A rare case of a 35 year old patient with primary testicular granulocytic sarcoma is described. In August 1997 the patient developed a painless testicular mass, low fever, dysuria, and bone pain treated unsuccessfully with antibiotics and NSAID. For the persistence of these symptoms, a testicular biopsy and then an orchiectomy was performed: histological diagnosis of diffuse infiltration by an unclassifiable malignant tumor was made. During staging, bone marrow (BM) biopsy and peripheral blood (PB) was normal, while CT scan revealed abdominal lymph nodes enlargement. In January 98 the patient was admitted to our hospital for further management. After a few days, patient suddenly developed leukemia and diagnosis of AML (FAB M5a) was made. Testicular mass specimens were reviewed and myeloblastoma with a monoblastic differentiation diagnosis was made. Cytogenetic analysis was abnormal: (47XY,+8; XY, +8, add(9q). After treatment with idarubicin, cytosine-arabinoside and etoposide (ICE) a BM and PB remission was achieved but pelvic mass persisted. In April 98 the patient had BM relapse and by reinduction treatment (ICE) a CR with disappearance of pelvic mass was obtained. In May 98 the patient underwent an allogeneic (aploidentical) bone marrow trans-

8 76 September 26-29, Torino-Lingotto, Italy plantation, after conditioning treatment with TBI and polichemoterapy. In October 1998 the patient presented a new BM and extramedullary relapse and therefore he was treated unsuccessfully with low dose cytosine arabinoside and infusion of total CD3+ donor lymphocytes. The disease was resistant to therapy and patient died in December Conclusion: Primary testicular granulocytic sarcoma is relatively rare, with only 4 documented cases reported in the literature. In our patient, primary testicular involvement occurred 6 months before the leukemic bone marrow infiltration, with initial bone marrow and peripheral blood normal pattern. The clinical outcome of our case, despite allogeneic BMT, confirms the poor prognosis of this disease. P010 PRIMARY GRANULOCYTIC SARCOMA: PRESENTATION OF A CASE M. TRESOLDI, P. ONIDA, A. MALINGHER, S. AGLIONE, C. SALMAGGI, L. CAMBA*, M. MARCATTI*, P. SERVIDA*, M. PONZONI# Department of Medicine, *Bone Marrow Transplantation Unit and Department of Hematology, #Department of Pathology, Ospedale San Raffaele, Milano Introduction: Granulocytic sarcoma (GS) is a tumor, composed by neoplastic myeloid cells, that involves extramedullary sites, more commonly bones, skin, soft tissues and lymphnodes. It develops during AML, myeloproliferative syndromes and myelodysplastic syndromes. Primary GS (PGS), that occurs in patients without any previous or concomitant blood disorder, is a rare disease (only 189 cases since 1965); if not treated it evolves into AML. The most difficult differential diagnosis is with large cell malignant lymphoma, but also with undifferentiated neoplasms, and it must be supported by specific stainings (MPO and CAE) and immuno-histochemical techniques for myeloid markers. As PGS is a systemic disease, it must be treated with the same type of polichemotherapy used for AML. Surgery and radiotherapy play a secondary role. Case report: 28 years old male patient, affected with right sciatica, fever and anemia (normal WBC and PLT). MNR showed pathologic tissue in T11, L1 and right iliac crest. There was evidence of a serum oligoclonal component at protein electrophoresis and of a reactive bone marrow plasmacytosis with neoplastic CD68+ and MPO+ elements in involved tissue biopsy (right PSIS); normal bone biopsy controlaterally. As a diagnosis of PGS was made, the patient received an induction chemotherapy (ICE scheme) was done and we observed PR 1 month afterwards. The course of the disease was complicated by a serious fungal pulmonary infection, treated by surgery. Then we observed CR 3 months after the single induction CT. The patient underwent a consolidation treatment with autologous peripheral blood stem cells transplantation. He is in CR after 3 years from diagnosis. Discussion: PGS is a rare disease, without characteristic clinical, laboratory and instrumental features, that must be diagnosed using myeloid specific markers. Its treatment is based on CT used for non M3 AML, with by Ara-C and an anthracycline, possibly followed by consolidation with donor or autologous bone marrow transplantation. Only such an aggressive treatment can ensure an improvement of the otherwise poor prognosis. P011 POLYRADICULONEUROPATHY AS A FORM OF RELAPSE IN A PATIENT WITH ACUTE MEGAKARYOCYTIC LEUKEMIA L. CALABRÒ, A. ALONCI, G. BELLOMO, C. QUARTARONE, F. DI BASSIANO, A. D ANGELO, S. NERI, C. MUSOLINO Division of Hematology, University of Messina Introduction: Central and peripheral nervous system recurrence is rare in acute myelocytic leukemia, however, it needs to suspect this complication when there are neurological clinical signs. We report an unusual case of polyradiculoneuropathy in a patient with acute megakaryocytic leukemia after 20 months in complete remission. Case Report: A 66 year old man was admitted to our hospital for slowly progressive, asymmetrical limbs weakness with numbness and burning dysesthesias. He was affected by long-lasting type 2 diabetes. Twenty months ago, he had been diagnosed as having acute megakaryocytic leukemia and achieved hematologic remission with combined chemotherapy (cytarabine and mithoxantrone). There was no lympho-

9 37 th Congress of the Italian Society of Hematology 77 adenopathy or organomegaly. On neurological examina-tion there were tetraparesis, absent tendon reflexes and flexor plantar responses; Lasegue and Kerning manoeuvres were positive. Morphologic examination of bone marrow and peripheral blood was consistent with complete hematologic remission. EMG demonstreted neurogenic changes with denervation in lower limb muscles. A magnetic resonance imaging scan (MRI) of the spinal cord showed an extradural infiltration in the spinal canal at C6-D1 level and a direct invasion of cauda. A lumbar puncture disclosed the presence in the cerebrospinal fluid of 700/ l cells with typical blastic morphologic features (CD33+, CD13+). A diagnosis of acute myelocytic leukemia relapse with intramedullary spinal cord tumor involvement during hematological remission was made. Our patient presented a chronic peripheral neuropathy likely related to diabetes, who developed a cervical and lumbosacral radiculopathy due to a neoplastic infiltration. We underline the complexity of diagnosis and the need to suspect a relapse when there are neurological clinical signs. P012 EXTRAMEDULLARY RELAPSE OF Ph1+ ACUTE MYELOID LEUKEMIA AND STERNAL CONSUMPTION AFTER AUTOLOGOUS PERIPHERAL BLOOD STEM CELL TRANSPLANT N. CANTORE, S. VOLPE, B. SANTULLI, G. MARCACCI, A. FOTINO, F. PALMIERI, E. VOLPE Servizio di Ematologia - Unità di Terapia Intensiva Ematologica e Trapianto - A.O. San G. Moscati - Avellino The majority relapses of acute leukemias after allogeneic or autologous stem cell tranplant occur predominantly in systemic forms or combined with an extramedullary relapse. Isolated extramedullary relapses after stem cell transplant are unusual events. A 56 year-old male with Ph1+ acute leukemia (FAB M5a) was transplanted with PBPC in August 1997 during first CR as part of EORTC-GIMEMA AML10 protocol. The conditioning regimen was BU-CY. In December 1998 he was admitted to our service because of thoracic pain and dyspnea. Thoracic x-ray and CT scan showed pleural effusion and consumption of a sternal portion was also found. Cytospin preparations of pleural effusion showed a tapetum of blast cells with FAB M5a morphology. The same immunophenotype of blast cells at diagnosis and relapse was found (CD13+, CD33+, HLA-DR+, CD4+, CD45RA+) except for lesser expression of CD11b and CD11c, and c-kit and MPO negativity. The blast cells were Ph1 positive at cytogenetic analysis and bcr/abl rearrangement at molecular analysis was found. Fine needle biopsy on osteolytic lesion of sternum showed a peripheral blood cells only and absence of marrow cells. The patient was treated with systemic chemotherapy (MICE) but unfortunately died of ARDS after 45 days. P013 LUNG TOXICITY FOLLOWING FLAN TREATMENT FOR ACUTE LEUKEMIA M. SALVUCCI,E. ZUFFA, R. ZANCHINI, A.L. MOLINARI, V. POLETTI*, A. ZACCARIA Hematology Unit, AUSL, S.Maria delle Croci Hospital, Ravenna; *Thoracic Diseases Department, AUSL, Maggiore Hospital, Bologna We report two cases of severe pulmonary toxicity following the administration of a chemioterapeutic regimen containing Fludarabine (FLUDA), 30 mg/mq/daily x 5 days, Cytarabine(Ara-C) 2g/mq/daily for 5 days and Mytoxantrone (MYTO) 6 mg/mq/ daily for 3 days.(flan). Case 1. A 31 year old man with ANLL M2 received FLAN therapy after acchieving partial remission with ICE. Seven days after therapy discontinuation, he developed fever, dyspnoea with marked oxygen desaturation. An high resolution computerized tomografy (HRCT) showed bilateral pulmonary ground glass opacities, consistent with interstitial involvement. BAL showed total cells / mm3 with erythrocytes and rare macrophages. BA biopsy showed haemorragic alveolitis. He received empirical antibiotical therapy and high dose prednisolone. Blood coltures were positive for Staph.Simulans. Six days later clinical symptoms and blood gas abnormalities had resolved, and a lung HRCT control showed a moderate improvement of the ground glass opacities. CR was obtained. A lung biopsy performed 20 days later showed a patchy interstitial mononuclear cell inflammation and intralveolar loose fibrotic bands, compatible with drug