ALBERT

Description: Abstract 3746 Poster Board III-682 Background Mantle cell lymphoma (MCL) is a rare subtype (3-9%) of Non Hodgkin Lymphoma (NHL) with a relatively poor prognosis (5-year survival 〈 40%). Although consolidation of first remission with autologous stem cell transplantation (ASCT) is regarded as “golden standard”, less than half of the patients may be subjected to this intensive treatment due to advanced age and co-morbidities. Standard-dose non-myeloablative radioimmunotherapy (RIT) seems to be a very efficient approach for treatment of certain NHL. However, there are almost no data available on the efficacy and safety of RIT in MCL. Methods and Patients In the RIT-Network, a web-based international registry collecting real observational data from RIT-treated patients, 115 MCL patients treated with ibritumomab tiuxetan were recorded. Most of the patients were elderly males with advanced stage of the disease: median age – 63 (range 31-78); males – 70.4%, stage III/IV – 92%. RIT (i.e. application of ibritumomab tiuxetan) was a part of the first line therapy in 48 pts. (43%). Further 38 pts. (33%) received ibritumomab tiuxetan after two previous chemotherapy regimens, and 33 pts. (24%) after completing 3-8 lines. In 75 cases RIT was applied as a consolidation of chemotherapy induced response; the rest of the patients received ibritumomab tiuxetan because of relapse/refractory disease. At the moment follow up data are available for 74 MCL patients. Results After RIT the patients achieved high response rate: CR 60.8%, PR 25.7%, and SD 2.7%. Only 10.8% of the patients progressed. For survival analysis many data had to be censored since the documentation had not been completed yet. The projected 3-year overall survival (OAS, fig.1 – image 001.gif) after radioimmunotherapy was 72% for pts. subjected to RIT consolidation versus 29% for those treated in relapse/refractory disease (p=0.03). RIT was feasible for almost all patients; only 3 procedure-related deaths were reported in the whole group. The main adverse event was hematological toxicity (grade III/IV cytopenias) showing a median time of recovery of Hb, WBC and Plt of 45, 40 and 38 days respectively. Conclusion Standard-dose non-myeloablative RIT is a feasible and safe treatment modality, even for elderly MCL pts. Consolidation radioimmunotherapy with ibritumomab tiuxetan may prolong survival of patients who achieved clinical response after chemotherapy. Therefore, this consolidation approach should be considered as a treatment strategy for those, who are not eligible for ASCT. RIT also has a potential role as a palliation therapy in relapsing/resistant cases. Disclosures: Off Label Use: Ibritumomab Tiuxetan (Zevalin) for MCL.

Description: Introduction: Venous thromboembolism (VTE) is an important problem for medical patients. In spite of the existence of evidence-based guidelines for prevention of VTE, prophylaxis for venous thromboembolism is underutilized. Objective: To assess the global and individual adherences (adjust to risk groups) to venous thromboembolism prophylaxis guidelines (VTEPG) in medical ill patients. Desing: Prospective observational study. Setting: The 50-bed medical floors of a university hospital. Material and Methods: Patients: All consecutively medically ill patients (pt) admitted during a 6-month period (n: 452). VTEPG: the guide divided medical patients in risk groups (G); G1: No need of VTEP (35 pt); G2: myocardial infarction (9 pt); G3: Stroke (21 pt); G4: high risk with thrombophilia, previous VTE, cancer (113pt); G5: respiratory and congestive heart failure, pulmonary infection (137 pt); G6: trauma (5 pt); G7: not included in previous groups, required an individual evaluation to asses VTE risk (112pt). Prophylaxis methods included: low dose unfractionated heparin (UFH) or low molecular weight heparin (enoxaparin 40 mg/d) and mechanical methods. Main outcome measurements: 1- Global: correct application of the guide (defined by a coincidence between the prophylaxis received and the recommendation); 2-Adjust to risk group. Results: Global adherence: Correct application of the guide was noted in 252 pts (56%); Adjust to risk group: GR1:71%; GR2:44%; GR3:62%; GR4:76%; GR5:55%; GR6:60% and GR7:26%. Conclusion: In our experience in medical patients global adherence to guides was 56%, the best adherence was observed in high risk groups 76% and the lowest 26% in those patients that need an individual risk assessment. This study and follow up permitted us to detect inaccurate prophylaxis uses and take corrective measures.

Description: Immune cytopenias (IC) frequently require prolongued administration of immunosupressors, especially when associated with lymphoproliferative disorders (LPD). Rituximab causes in vivo selective destruction of B lymphocytes and supresses the production of antibodies. Three mechanisms are involved; complement dependent cytotoxicity, antibody dependent cellular citotoxicity and the induction of apoptosis. We present 10 patients with IC: 8 autoimmune hemolytic anemia (AIHA), and 2 AIHA plus immune thombocytopenia (Evans’ syndrome). Seven patients had IC associated with LPD, and 3 were idiopathic. LPD were: 3 follicular lymphoma (1 Grade 1, 1 Grade 2, 1 Grade 3), 1 small lymphocytic lymphoma, 3 chronic lymphocytic leukemia. Three patients with idiopathic cytopenias had a long history of recurrent AIHA (2) and Evans’ syndrome (1). Ages ranged between 43 and 81 (median 63 yrs); 6 were female gender and 4 male. All AIHA cases, except 1 pts with cryogrobulins, presented with warm IgG antibodies. Previous evolution included splenectomy in 2 pts and all pts received multiple courses of immunosupression with steroids and others, like azathioprine and cyclophosphamide. All patients with LPD received one or more chemotherapeutic regimens with alkylating agents, fludarabine or CHOP combination. Median time to IC in 7 pts with LPD was 75 months (2–228). Idiopathic cases had 12, 132 and 204 months of previous evolution. Rituximab was administered at 375 mg/m2 every 1 to 3 weeks for 3 to 8 doses (median 4). Six pts received rituximab as monotherapy and 4 pts in combination with chemotherapy. Toxicity was mainly related to the first cycle of rituximab and consisted in chills and fever grade I-II in three pts. Clinical resolution of cytopenia occured in 9/10 pts (90%). 4 of them (44%) resolved with negative direct antiglobuline test. Median time to response was 4 weeks (2–8). One AHIA died with hemolysis progression, six months after rituximab, and 1 pts with AHIA and follicular lymphoma died 8 months after rituximab treatment with progression of LPD without evidence of hemolysis. The rest of the patients remained without IC for 2–42 months (median 18). Rituximab, originally designed to treat B-cell neoplasms, is an active immunosupressive agent in either lymphoproliferative associated or idiopathic autoimmune cytopenias even in non splectomized pts. Its use may avoid the secondary effects of long term administration of steroids, alkylating agents or transfusions.

Description: Hereditary hemorrhagic telangiectasia (HHT) is a relatively uncommon, autosomal dominant disorder characterized by telangiectases that develop in the skin, mucous membranes, and visceral organs. Mucous localization may seldom bleed profusely, especially epistaxis and upper gastrointestinal (GI) tract. Effective drug treatment is not well established, and multiple blood transfusions and endoscopic or surgical procedures may be the ultimate solution to the frequently bleeding HHT patient. Danazol (DZ) is a mild androgen that has been used in small series of HHT pts with ambiguous results. Its toxicity profile in long standing administration is now well known. Eighteen patients with HHT with transfusion requirements (TR) were treated with DZ at 400–600 mg/daily for the initial three months and 200–400 mg/daily thereafter as a maintenance treatment. At the time of initiation of DZ therapy, median age was 54 yr-old (32–73), nine were female and 9 male, and the median previous TR was 16 RBC units/yr. (2–46). All patients had epistaxis and oral cavity bleeding, with 2 additional upper gastrointestinal tract active bleeding that were detected in ten patients in which an upper GI endoscopy was performed. One patient had a cerebral angioma, surgically treated. None had pulmonary fistula. All patients had some kind of iron treatment. DZ was the first drug treatment intended to reduce the HHT bleeding in 10/18 pts. Median follow-up was 7 years (1.2–14) and two pts were lost to follow-up at 4 and 11 years respectively. At three months of DZ therapy, 12/18 pts (66.6%) showed a remarkable reduction of bleeding, and in 6 patients that showed no response, DZ treatment was stopped. In 7 pts (39%) TR dropped to none and in 5 pts median RT dropped from 22 RBC units/yr. to 10 units/yr. Two of responders had a relapse with upper GI tract bleeding and 1 pts with epistaxis within the first 2 years of DZ treatment. Attempts to reduce the maintenance dose below 200 mg/daily were related to new bleeding or worsening of the active sites. None of the long standing DZ therapy had any significant toxicity. DZ treatment have shown efficacy and safety in this cohort of HHT patients. Mecanism of action may involve the increase of synthesis or expression of ALK-1 dependent proteins and less likely of endoglin. We propose DZ as a first line treatment for the transfusion dependent HHT patients.

Description: Background: 90Y-ibritumomab tiuxetan (Zevamab®; ZEV; Bayer-Schering Pharma- Argentina) has been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Methods: Between Sep. 2005 and Feb. 2008, 45 patients (pts) [22 F & 23 M; median age 62 yrs (45–83)] with refractory/relapsed lymphoma were enrolled. Diagnoses: 37 follicular lymphoma (FL), 5 were mantle cell lymphoma (ML) and 3 transformed lymphoma (TL); 18 pts had bulky disease, 8 had bone marrow involvement and 21 had stage III–IV disease. Median time from diagnosis was 5 yrs (0.5– 29). Twenty two pts had received 1–2 previous treatments, and 23 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. ZEV was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and the same day of the ZEV administration, pts received standard rituximab 250 mg/m2. In 3 pt, ZEV was part of the conditioning regimen of autologous bone marrow transplantation. Results: Forty pts were evaluable for response: 34 (86%) pts responded – 19 CR (48%), 15 PR (38%). Overall survival and PFS for the entire group at 18 months was 63% and 37% respectively, with a median follow-up of 12 months (1–29 months). Of the 45 patients, 5 pts (11%) had died before third month and response was not assessed, 6 pts (13%) did not respond, 3 (7%) died with response from other causes, 14 pts (31%) responded and subsequently relapsed. Finally 17 pts (38%) continue to be in response, 9 (20%) lasting more than twelve months (long lasting responders). Slight differences in duration of response and survival were observed between FL vs ML and TL favouring FL (RR 2.047). Forty six per cent of pts required filgrastim for neutropenia, 24% required platelet transfusions, 22% had neutropenia plus fever and were admitted for complicated pancytopenia, and 20% required red blood cells transfusion. Two patient died 30 & 40 days after treatment with hypoplastic bone marrow complicated with sepsis in the post autologous bone marrow transplantation period. Four pts with previous bone marrow transplantation required filgrastim, transfusions and 2/3 had febrile neutropenia. Conclusion: Our experience with ZEV in relapsed and refractory FL shows 48 % CR. Even heavily treated pts that had previous bone marrow transplantation were able to receive ZEV, although they required extra support. Our experience supports the use of ZEV in relapsed and refractory lymphomas even after autologous bone marrow transplantation.

Description: To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy. Jurczak:Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.

Description: The radionucleid conjugate with monoclonal antibodies (antiCD20/90Y-ibritumomab tiuxetan) have been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Between September 2005 and August 2007, 41 patients with refractory/relapsed lymphoma were enrolled. Median age was 62 yrs old (45–83). Twenty were women and 21 were men. Thirty three were follicular and 5 were mantle cell lymphoma and 3 transformed lymphoma. Eighteen patients had bulky disease, 8 had bone marrow involvement and 21 had stage III-IV disease. Median time from diagnosis was 5 years (0.5–29). Twenty one had received 1–2 previous treatments, and 20 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. 90Y-Ibritumomab (Zevamab™ Bayer-Schering Argentina) was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and on the same day of the immunoconjugate administration, pts received rituximab 250 mg/m2. Thirty eight were evaluable for response. Thirty four (89%) pts responded: 20 CR (53%) and 14 PR (36%). With a median follow-up of 10 months, 60% of pts were expected to continue in CR at 18 months. Overall survival at the same period for the entire group was 89%. Nineteen pts (46%) required filgrastim administration for neutropenia, Ten pts (24%) required platelet transfusions, 10 pts had neutropenia plus fever and they had to be admitted for complicated pancytopenia, 8 pts required red blood cells transfusion. Two patient died 30 and 40 days after treatment with hypoplastic bone marrow complicated with septicemia and in the post autologous bone marrow transplantation period, respectively. Four pts with previous bone marrow transplantation, required filgrastim, transfusions and 2/3 had febrile neutropenia. Our experience with 90Y-ibritumomab in relapsed and refractory folicullar lymphoma shows 53% CR. Even heavily treated pts, that had previous bone marrow transplantation were able to receive the radioimmunoconjugate, although they required extra support. Our experience favours the use of 90Y-Ibritumomab tiuxetan in relapsed and refractory lymphomas even if they had received previous autologous bone marrow transplantation.

Description: Abstract 1040 Background: Iron(III) polymaltose complex (IPC) shows similar efficacy to ferrous sulfate for the treatment of iron deficiency anemia but with superior tolerability. The stable structure of IPC prevents unregulated uptake of iron from the gut, avoiding an increase in non-transferrin bound iron with associated oxidative stress. IPC similars have been developed which vary in structure from the originator IPC preparation (Maltofer®, IPCM). A direct comparison between the originator and IPC similars in their potential to induce oxidative stress has not been performed. In this study, we compared acute and early toxicity in the gastrointestinal (GI) tract and liver in healthy rats randomized to IPCM, an IPC similar (Vitalix, IPCV) or a control arm. Methods: LD50 values were determined by administering single increasing doses of IPCM or IPCV (each n=12) and counting deaths at 24 hours. Three groups of rats (each n=12) then received doses equivalent to 10% of LD50 for IPCM (280 mg iron/kg/day) or IPCV (280 mg iron/kg/day), or tap water (controls) for 28 days. Iron-induced lesions in the GI tract were scored: 1, superficial 1–5 hemorrhagic points; 2, superficial 6–10, hemorrhagic points; 3, sub-mucosal hemorrhagic lesions with small erosions; 4, severe hemorrhagic lesions and some invasive lesions. Iron deposits (Prussian blue) and tissue ferritin in the liver and small intestine were assessed by immunohistochemistry. Ferritin immunostaining in the small intestine was scored: 1, none; 2, mild; 3, moderate; 4, very intense. Results: LD50 was the same for IPCM and IPCV (〉2800 mg iron/kg). Animals treated with IPCV had lower food consumption and body weight vs those treated with IPCM and controls. IPCV was associated with increased serum iron and transferrin saturation vs the IPCM group, suggesting bypass of the regulated iron uptake system. Microscopically, the villi/crypt ratio and the number of Goblet cells per villi in the small intestine were significantly lower with IPCV vs IPCM or controls, and the number of eosinophils per villi was increased in IPCV-treated animals. Gross anatomy and microscopy findings showed that IPCV- treated animals experienced variable degrees of inflammation in the GI tract while the IPCM and control groups showed no lesions. Ferritin immunostaining of liver tissue indicated that iron was appropriately stored in IPCM-treated within Kupffer's cells (Prussian blue). Ferritin deposits in the small intestine were also higher with IPCM. Differences were statistically inferior for IPCV versus IPCM for clinical and iron parameters, gross anatomy, microscopic findings and ferritin immunostaining (Table). Conclusions: IPCV showed the same LD50 as IPCM, but considerably greater early GI tract toxicity. Increased numbers of eosinophils in the IPCV group suggest an allergic component of the small intestine injury in these groups. Markers of iron transport and distribution indicated less well controlled uptake and storage following ingestion of IPCV compared to IPCM. The increased levels of ferritin deposits in the small intestine of IPCM-treated animals suggests that excess iron is stored in the gut wall instead of saturating the iron transport mechanism and increasing non-transferrin bound iron levels. Disclosures: Toblli: Vifor (International) Ltd: Consultancy, Research Funding.

Description: Background. In our experience, in Argentina, the use of rituximab + chemotherapy in relapsed/refractory CD20+ follicular (FL) non-Hodgkin’s lymphoma results in 100,000/mm3 and bone marrow involvement 5 cm). Three pts were Ann Arbor stage I or II and 7 pts were stage IV. Three pts had received 1–2 cycles of rituximab + chemotherapy and 7 pts had received 3–5 previous cycles. Three pts had undergone autologous transplant. Pts received rituximab 250 mg/m2 IV on days 0 and 7. After the second dose of rituximab, pts received 11 MBq (0.3 mCi) 90Y-Zevalin per kg or 15 MBq (0.4 mCi) 90Y-Zevalin per kg based on platelet counts, with a maximum dose of 32 mCi. Blood counts were monitored weekly until week 10 post-treatment and monthly thereafter. Patient tumor response was reevaluated 3 and 6 months after treatment according to standard criteria. Results. Five pts received a complete dose of 0.4 mCi 90Y-Zevalin per kg and 5 received a reduced dose of 0.3 mCi 90Y-Zevalin per kg. The overall response rate was 60% (CR = 5, PR = 1). Table 1 summarizes the responses. The 5 pts with a CR remained disease-free 8 months later. The pt with a PR progressed with adenopathies and visceromegaly 7 months after treatment. Seven of 10 pts experienced hematologic toxicity: 5 of these 7 pts required G-CSF because of grade 3/4 neutropenia and 3 of these pts developed neutropenic fever. Four of the 7 pts required platelet transfusions and 2 of them required red blood cell transfusions. All 3 pts with previous autologous transplant were in the group with hematologic toxicity. All of these pts required G-CSF and transfusion support, and 2 of these 3 pts were admitted to the clinic for this treatment; hematologic recovery occurred by week 9 post-treatment. Conclusion. The use of 90Y-Zevalin in the relapsed/refractory NHL setting resulted in better response rates and longer disease-free survival than with standard chemoimmunotherapy. Our finding with 50% CR in a heavily pretreated cohort, including 42.8% CR in stage IV pts and 33% CR after autologous transplantation, is encouraging. We are continuing to follow these patients. Table CR PR NR/PD Previous transplant (n=3) 1 1 1 Mantle cell (n=1) 0 0 1 Follicular (n=9) 5 1 3 Tumor volume 〉 5cm (n=4) 1 0 3 Tumor volume

Description: The coexistence between Chronic Myeloproliferative Syndrome (CMS) and Chronic Lymphoproliferative syndrome (CLS) is a rare event with a few cases reported in literature. This association generates the hypothesis about whether both syndromes derive from the same malignant clonal cells or from independent ones with a common leukemogenic stimulus. In some cases both diseases occur simultaneously while others develop sequentially after exposure to alkylating agents or radiation therapy. We report four patients treated at our center who developed both myeloproliferative and lymphoproliferative syndromes. The CMS were two cases of Myelofibrosis (MF) and two cases of Chronic Myeloid Leukemia (CML). The CLS were two cases of Chronic Lymphocytic Leukemia (CLL), one case of Follicular Lymphoma and one case of Hairy Cell Leukemia. Patient A is a 66-year-old man who was diagnosed with CLL. Inmunophenotyping of peripheral blood (PB) and bone marrow (BM) showed CD45, CD19, CD20, CD5, CD23, CD11c, FMC7, CD38 positive cells with lambda light chain restriction. The BM biopsy showed infiltration of CLL with slight increase of reticulin. After six months, he developed severe tricytopenia. A new BM biopsy showed morphologically abnormal megakaryocytes and increased reticulin compatible with MF plus coexistence of CLL. Heterozygous JAK2 V617F mutation was detected in PB. Nuclear Magnetic Resonance was compatible with MF. He was treated with rituximab with disappearance of the leukemic clone. Treatment with thalidomide (50 mg/day) and dexamethasone (4 mg/day) was started because of rapidly progressing idiopathic MF. Nowadays we observe an improvement of the hematological counts. Patient B is an 88-year-old woman diagnosed with Philadelphia (Ph)-positive CML in chronic phase who was treated with hydroxyurea (500–1000 mg/day). Twenty months later, she developed CLL with inmunophenotyping of PB and BM lymphocytes positives for CD5, CD19, CD20, CD22 and CD23 with kappa light chain restriction. The 13q14 deletion was detected by FISH in the lymphoid cells. The BCR/ABL rearrangement by FISH was observed in all myeloid elements but none in the lymphoid cells. The patient started with chlorambucil (10 mg/m2/day for 15 days per month for 10 months). Patient C is a 73-year-old man who was simultaneously diagnosed with Ph+ CML and Follicular Lymphoma. He was treated with hydroxyurea for the CML and subsequently imatinib was started. At present, 7 years after the initial diagnosis, he developed a blast crisis. Patient D is a 50-year-old woman who was diagnosed with MF with myeloid metaplasia. Physical examination revealed splenomegaly. BM inmunophenotyping was normal. The patient received splenic irradiation, prednisone and thalidomide showing recovery of hematological counts. After 3 years she developed Hairy Cell Leukemia with inmunophenotyping of PB positive for CD45, CD19, CD20, CD11c, CD23, CD25, CD103, HLA-DR and CD79b with lambda light chain restriction. Some authors suggest that this association between CMS and CLS can be originated from a same pluripotent stem cell. Others suggest that coexistence between CMS and CLS is secondary to proliferation of two different progenitors, perhaps, under a single leukemogenic stimulus. Based on the incidence of these diseases, others propose that coexistence is a matter of chance. Of the 4 patients above mentioned, only patient B showed the independent origin of both disorders. As far as we know, this is one of the few reports in which cytogenetic, FISH and molecular studies shows CLL development during the course of CML, arising from a distinct Ph-positive stem cell. Although chemotherapy may increase the risk of secondary malignancies, this is not the case for patients A, B and C since they had not received any treatment before the diagnosis of the second pathology. We find that further investigation is needed to understand the mechanisms that originate the association of this disorders.