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Introduction:DREAMM-3 (NCT04162210) is a randomized study comparing single-agent belantamab mafodotin, a first-in-class antibody-drug conjugate targeting B-cell maturation antigen, to a standard-of-care regimen, pomalidomide plus dexamethasone (Pd). This post-hoc analysis from the DREAMM-3 trial evaluated the safety and efficacy of long-term treatment (≥52 weeks) with belantamab mafodotin compared with Pd, as well as the effects of dose modifications, in adult patients with relapsed/refractory multiple myeloma (RRMM) at third line of therapy or later.

Introduction: Real-world (RW) studies provide valuable insights and complimentary data that may not be covered by clinical trials. In general, RW studies customarily collect data retrospectively, but it is important to have prospective RW studies that can contribute in a better way to reduce possible bias and qualify information. Besides that, RW data fully represent patients followed in a routine

Introduction:the treatment with CAR-T cells in Brazil is challenging because it requires a highly qualified multidisciplinary team trained in new clinical pathways to take care of these patients.

Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P< .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P< .0001).

Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P < .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P < .0001).

Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication in hematopoietic stem cell transplant (HSCT) recipients. To determine the impact of pretransplantation hyperferritinemia on the risk of SOS after HSC transplantation, we retrospectively studied 427 HSCT recipients (179 autologous and 248 allogeneic). Serum ferritin levels were measured before transplantation. Patients with and without a diagnosis of SOS were compared regarding demographics; underlying disease; transplant characteristics; receipt of imatinib, busulfan, total body irradiation, gemtuzumab, vancomycin, acyclovir, or methotrexate; and baseline serum ferritin. Univariate and multivariate (stepwise logistic regression) analyses were performed. SOS was diagnosed in 88 patients (21%) at a median of 10 days (range, 2-29 days) after transplantation. By multivariate analysis, allogeneic HSC transplantation (odds ratio [OR] = 8.25; 95% confidence interval [95% CI], 3.31-20.57), receipt of imatinib (OR = 2.60; 95% CI, 1.16-5.84), receipt of busulfan (OR = 2.18; 95% CI, 1.25-3.80), and ferritin serum level higher than 1000 ng/dL (OR = 1.78; 95% CI, 1.02-3.08) were risk factors for SOS. A ferritin serum level higher than 1000 ng/dL in the pretransplantation period is an independent risk factor for SOS. The results suggest the need for prospective studies addressing the use of iron chelation in the pretransplantation period.

Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication in hematopoietic stem cell transplant (HSCT) recipients. To determine the impact of pretransplantation hyperferritinemia on the risk of SOS after HSC transplantation, we retrospectively studied 427 HSCT recipients (179 autologous and 248 allogeneic). Serum ferritin levels were measured before transplantation. Patients with and without a diagnosis of SOS were compared regarding demographics; underlying disease; transplant characteristics; receipt of imatinib, busulfan, total body irradiation, gemtuzumab, vancomycin, acyclovir, or methotrexate; and baseline serum ferritin. Univariate and multivariate (stepwise logistic regression) analyses were performed. SOS was diagnosed in 88 patients (21%) at a median of 10 days (range, 2-29 days) after transplantation. By multivariate analysis, allogeneic HSC transplantation (odds ratio [OR] = 8.25; 95% confidence interval [95% CI], 3.31-20.57), receipt of imatinib (OR = 2.60; 95% CI, 1.16-5.84), receipt of busulfan (OR = 2.18; 95% CI, 1.25-3.80), and ferritin serum level higher than 1000 ng/dL (OR = 1.78; 95% CI, 1.02-3.08) were risk factors for SOS. A ferritin serum level higher than 1000 ng/dL in the pretransplantation period is an independent risk factor for SOS. The results suggest the need for prospective studies addressing the use of iron chelation in the pretransplantation period.

Patients with multiple myeloma (MM) have an increased risk for severe infections due to both the disease and anti-myeloma therapies. During the COVID-19 pandemic, case series of MM patients have demonstrated a poor outcome in those who required hospitalization due to COVID-19, and there are few data regarding those managed out of hospitals or risk factors for hospitalization. In Brazil, where the scenario is of restricted resources to treat MM patients and large numbers of COVID-19 cases and related death, the outcome can be even worse. Objective: To assess risk factors and outcomes of COVID-19 in Brazilian patients with MM.

De Queiroz Crusoe: Janssen: Research Funding. Hungria: Takeda: Honoraria; Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel ; Abbvie: Honoraria; Sanofi: Honoraria, Other: Support for attending meetings/travel .

Introduction:An epidemiological database is an important tool to characterize the population disease distribution, long-term effects of the diseases, impact of evolving treatments, to identify adverse events (AE) and their possible mitigation and to improve the healthcare system. Another important reason to create a database is to rapidly identify, recruit and enroll individuals for research activities. Based on these, the Brazilian Multiple Myeloma Study Group (GBRAM) developed an electronic database platform with the intention of prospectively registering the MM cases diagnosed at Brazilian healthcare services. Methods:This is a prospective, multicenter, open, epidemiological study, based on an electronic system register. Patients diagnosed with MM after January 1, 2018 have been included. The eligibility criteria were: intent-to-treat (ITT) MM patients, aged over 18 years and under care in any healthcare system (private, public and academic). All clinical and laboratory data, prognostic profiling, treatment patterns and responses, AE and survival were compiled. The data were analyzed with the NCSS® 2020 software. This project is registered in the Brazilian study platform control (Plataforma Brasil) linked to federal health authorities by the number CAAE-05340918.3.1001.8098. Results:To date, 1,113 patients at 44 reference centers were included. The median age was 64 (25 -96) years and 578 (52%) were male. According to the ECOG performance status: 0 = 185 (16.5%), 1 = 257 (23.2%), 2 = 144 (13%), 3 = 105 (9.5%), 4 = 62 (5.5%) and the not available data (NA) = 359 (32.3%). The ISS 1, 2, and 3 were 219 (19.7%), 286 (25.7%) and 406 (36.5%), respectively, the NA being 202 (18.1%). MM isotypes were 524 (47.1%) IgG, 202 (18.2%) IgA, 192 (17.2%) free-light chain, 4 (0.5%) IgM, 7 (0.8%) biclonal, 9 (0.7%) non-secretor and 175 (15.5%) NA. Regarding the treatment backbone, 427 (38.4%) patients received immunomodulators (IMID- thalidomide), 277 (20.4%), proteasome inhibitors (PI-bortezomib), 84 (7.6%), the combination of PI + IMID, 72 (6.6%), combinations with anti-CD38 monoclonal antibody (Daratumumab) and 253 (27%), other treatments. Based on the ITT analysis of 1003 cases, 636 (63.4%) patients were planned for bone marrow transplantation (BMT) and 367 (36.6%) were ineligible. After a median follow-up of 14.0 months, 150 (23.6%) of the planned patients had undergone the procedure, 284 (44.7%) had not yet been submitted and 202 (31.7%) had NA data. The overall survival (OS) was 80.9% for the total group at 20 months, 73.5% for ineligible and 95.5% for eligible. There was a significant improvement in eligible patients who had performed BMT, as compared to those who had not, HR 0.15 (0.09 - 0.26), p< 0.0001. A total of 142 deaths (12.8%) occurred, 51 (36%) of them being during the first 180 days. Discussion:Due to the lack of a reliable national register and the undoubtable need for a better understanding of MM for the development of public health and patient support measures, GBRAM has developed and built an electronic platform. This epidemiological study prospectively enrolled patients diagnosed since January 2018 and is of a nationwide scope. To date, 1,113 new cases were included. Despite the short follow-up, this analysis has identified differences in survival, comparing ISS stratifications and whether a BMT was performed or not. Conclusion:This project demonstrates the feasibility and importance of electronic platforms in the compilation of MM populational data for a better understanding of the clinical characteristics, treatment patterns and outcomes in the real world, permitting a clearer perception of local issues and thus, addressing possible improvement in public healthcare policy, such as the improvement of BMT access.

Puig: Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Mateos:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction:Several studies have shown the role of the immune system in the development of MM, but there is no systematic description of normal B-cell regeneration during treatment points. Recently, EuroFlow consortium has developed NGF panel with high sensitivity to evaluated MRD and potentially, to assess of the normal B-cell compartment of patients with MM. Aims:Here we evaluated the B cell regeneration pattern of bone marrow (BM) from patients with MM by Next Generation Flow (NGF)cytometry at diagnosis and at minimal residual disease (MRD) time points of treatment. Material and Methods:Overall 190 samples of MM patients (45% female and 55% male, median age of 65 years - 37 to 87 years, of which: 16 at diagnosis, 30 post-induction, 76 D+100, 59 maintenance/consolidation and 9 out of treatment, and 8 samples of BM healthy donor - HD (≥ 50 years). At the moment treatment, D+100 were included samples from two research centers: HCS/USAL (n=64) and HUCFF/UFRJ (n=12). Induction regimens were composed of triple protocols (PI + IMIDs + Steroids); followed by high doses of melphalan with ASCT, while patients in maintenance/consolidation followed second line treatment regimens - IP+IMIDs and/or PIs+Steroids and/or monoclonal antibodies or INF or IPs. All samples of BM were subjected to bulk cell lysis with ammonium chloride solution for >107cell acquisition and labeled with a combination of 10 antibodies - Panel EuroFlow MM MRD.Results:Of the 174 post treatment samples, 36% presented MRD- and 64% MRD+. At diagnosis, patients exhibit a significant reduction of precursors B cells and normal plasma cells (nPC) relative to HD, probably a reflection of the occupation of their binding sites by cPC. At post-induction, there was an increase in precursors B, compared to MM patients at diagnosis, associated with a reduction of mature B-cell (transitional/naïve and memory), regardless of MRD status. Concerning the nPC compartment, a reduction was observed, relative to HD. During treatment, reduction of the tumor burden leaves these sites free for precursors B, which rapidly recover while leads to a drastic decrease in mature B cells and regeneration of the precursors to mature B-cells is slower. On the other hand, in D+100, independent of the MRD status, there was a post treatment medullary recovery, with an increase in B precursors and transitional/naïve B-cells, in contrast, with a reduction of memory B-cells. Out of treatment, we observed a recovery of precursors B, mature B-cells and increase of nPC, but the immune recovery of these nPC is not sufficient to reach the levels of a healthy individual. Conclusion:NGF emerges as an optimal approach for simultaneous assessment of the BM regeneration profile of B-cells and the MRD status.After starting therapy, MM patients re-establish the compartments of B-cell precursors and transitional/naïve B-lymphocytes; however, memory B cells and nPC do not recovery until the end of treatment. This study is a starting point for exploring the importance of the B cells of the medullary microenvironment in the MM. Its potential impact on patient outcome deserving further investigations

Introduction:T-cell and natural killer (NK)-cell lymphomas encompass a heterogeneous spectrum of malignancies with variable degrees of biological and clinical aggressiveness and different patterns of nodal/extra nodal dissemination. Despite advances in understanding of their genetic landscape, treatment options for these tumors are limited and survival remains dismal especially in patients (pts.) who relapse/progress after frontline treatment. Therefore, development of new active agents is a pressing medical need in this setting. The unconventional alkylator BDM and HDACi are clinically effective in pts. with recurring disease and the combination of these agents was suggested as a way to overcome early resistance and improve response and survival rates in T-cell tumors. Since EDO-S101 is a fusion molecule that combines the active structures of BDM and the pan-HDACi vorinostat to simultaneously damage DNA and block damage repair, we investigated its antitumor activity in preclinical models of human T- and NK- lymphomas.

Introduction:Previous studies have described the profiles of patients with MM registered in LA (Haematologica 2008; Ann Hematol 2017) and in Asia (Am J Hematol 2014). We used these two datasets to compare patient profiles and overall survival (OS) in these two world regions.

Background- The treatment of multiple myeloma has evolved significantly in the last decade and combinations of the new drugs have allowed better responses and significant gain in survival. Studies comparing different chemotherapy combinations before transplant suggest that the triple combo is superior to double. The use of bortezomib as backbone in these combos has been identified as superior to other drugs. Unfortunately bortezomib is not part of the drugs available for use in the Brazilian public health system to myeloma treatment and the only available drug is thalidomide. Comparisons between different triple combinations are rare in the literature. In the present study we compared two different triple combinations composed of bortezomib + cyclophosphamide + dexamethasone (VCD) versus thalidomide + cyclophosphamide + dexamethasone (CTD) in order to identify which of the two combinations lead to the best response after 4 cycles before bone marrow transplantation for eligible new diagnose patients with multiple myeloma.

Mehrling: 4Mundipharma-EDO GmbH, Basel, Switzerland: Employment. Pinto:Takeda, Celgene, Roche, TEVA: Honoraria; Takeda: Research Funding.

Background:The highly unfavorable outcome of patients with recurrent HL, who progress after stem cell transplantation or are ineligible for such procedure make the development of new active agents an impellent medical need in this clinical setting. EDO-S101 is fusion molecule combining the DNA damaging effects of bendamustine (BDM) with the pan-histone deacetylase (HDAC) inhibitor, vorinostat. Given that BDM and HDAC inhibitors are active agents in recurrent HL we investigated the preclinical activity of EDO-S101 in this malignancy.

Little is known about the incidence and clinical features of Multiple Myeloma (MM) in Latin America. A clinical registry of Latin American (LA) patients with MM represents an opportunity to gain insight into the prevalence of the disease in this region, the patterns of care and the current treatment status in different LA countries.

Little is known about the incidence and clinical features of Multiple Myeloma (MM) in Latin America. A clinical registry of Latin American (LA) patients with MM represents an opportunity to gain insight into the prevalence of the disease in this region, the patterns of care and the current treatment status in different LA countries.To characterize the demographic and clinical features of patients with multiple myeloma from five LA countries (Brazil, Argentina, Chile, Mexico and Peru) and to create a LA database on MM; in addition to investigating the patterns of care for MM patients in Latin America.This is an observational, non-intervention study, with a prospective evaluation of data. Eligible patients were diagnosed with multiple myeloma, between January 1, 2005, and December 31, 2007, at any one of the participating centers, regardless of disease stage or treatment modality. The follow-up period extended to at least 5 years for each patient (December 31, 2012).Eight hundred and seventy six patients were included. The median age was 60 years old (25-97), 53.4% male and 46.6% female. The median follow-up was 31.4 months, and the median overall survival was 57 months. The median overall survival to patients who received high-dose chemotherapy was 77 months and for patients who received conventional chemotherapy was 48 months (p<0.001). The multivariate prognostic model included patient baseline variables that were associated with mortality in the Kaplan-Meier univariate analyses. Only hypercalcemia, DSS II and III, ISS stage III andnon- high-dose chemotherapy were independent predictors of mortality.This current study, which is the largest case series of MM patients in Latin America, recognizes the feasibility of large, collaborative, observational studies among various tertiary-care hematology centers in Latin America.We will present more details related to the demographic and most frequently used treatments in Latin America for newly diagnosed and relapsed patients in these LA countries.No relevant conflicts of interest to declare.

In recent years stem cell transplantation (SCT) has been used increasingly for the treatment of different oncohematological diseases. Although improvements have been obtained, bacterial, viral and fungal infections continue to represent the major challenge. SCT in MM increases patient's vulnerability to infections due to immunological changes related to the conditioning and the disease itself. The increased cytokine expression, that involve the pathogeneses of multiple myeloma, like TNF-α, IL-6 and 10, have an important relationship with the immune response and disease progression. Single Nucleotide Polymorphisms (SNPs) in the promoter region of cytokine genes are responsible for altering the levels of expression, thereby affecting the evolution of the disease and the immune response. It has been considered that the immune response is modulated by the interaction of several factors or gene products on related metabolic pathways. We have hypothesized that SNPs in the IL-6, IL-10 and TNF-αgenes may be associated with the susceptibility to infection, either when considered alone or combined in haplotypes. More importantly, however, is the gene-gene interaction analysis of the SNPs in these biologically related genes.We performed association analysis of single polymorphisms, the combination of SNPs in haplotypes and epistasis or gene-gene interaction analysis.We have clinically assessed the infection status of the patients for the following conditions: fever of unknown origin, death during the neutropenic phase, fungeous blood stream infection (F.BSI), superinfection, bacteremia (Gram-positive BSI and Gram-negative BSI), invasive fungeous infection. Genomic DNA was extracted from mobilized peripheral-blood stem cells of 148 patients. Genotyping was carried out for the SNPs IL-6 (-174G/C), IL-10 (-1082A/G, -592A/C e -819T/C) and TNF-α (-308G/A) using the Real-time PCR assay and PCR followed by restriction length fragment polymorphism (PCR-RFLP). Haplotype frequencies were estimated with Haplo.stats® and all the other statistical analysis were performed with SPSS®. Gene-gene interaction analysis was performed by multifactor dimensionality reduction (MDR®) method.We have not observed deviations from the Hardy-Weinberg equilibrium for the genotypes. The TNF-α polymorphism was significantly associated with fever of unknown origin (p=0.03), IL-6 polymorphism was associated with fungemia (p=0.04) and death during neutropenia (p=0.02), and IL-10 polymorphism was associated with superinfection (p=0.02). Interestingly, the IL-10 “ATA” haplotype was also associated with superinfection (p=0.016). In addition, the “ATA” haplotype was associated with F.BSI (p=0.004) and the “ACC” haplotype was associated with Gram-negative bacteremia (p=0.040) and superinfection (p=0.048). Epistasis analysis revealed a significant interaction model between TNF-α G308A and IL-6 G174C polymorphisms when compared the groups with and without bacteremia (Balanced Accuracy = 0.6021, Cross Validation Consistency = 10/10, p=0.0380).The results showed that despite the primary predisposition to infection typical of multiple myeloma, the presence of the variants studied significantly affected the susceptibility to serious infections and outcomes of ASCT. Moreover, our findings from epistasis analysis indicate that the interaction of polymorphisms may be more important than the effects of single polymorphisms for the immune response associated with the infection susceptibility in ASCT.No relevant conflicts of interest to declare.

Abstract 2026

Thalidomide (Thal) is a pro-apoptotic, immunoregulatory and antiangiogenic agent for MM. Although it is used since the 90's, the optimal combined treatment remains inconclusive. This is a preliminary analysis of the first Latin American prospective open-label study comparing three different combinations with Thal for MM patients not eligible for autologous SCT.Eligible patients were randomized to one of the three arms and received nine 28-days induction cycles. All patients received Thal(100–200mg/d) and one of the following: A- Cyclo (50mg/d)+ Dexa (40mg/D1-4, 15–18 in cycles 1 and 2, D1-4 in cycles 3 to 9), B- Dexa (40mg/D1-4, 9–12, 17–20 in cycles 1,3,5,7 and 9, D1-4 in even cycles) or C- Mel (4mg/m2/7d)+ Pred (40mg/m2/7d). Thereafter, they were randomized to maintenance treatment until progression disease or unacceptable toxicity, as follows: A1-Thal (100mg/d)+Pred (50mg/each other day) or B1-(Thal 100mg/d). All patients received aspirin as thromboprophylaxis and sulpha-trimetroprim as prophylaxis for infection. If indicated, they received biphosphonate monthly for 24 months, and then quarterly. Before study initiation, informed consent was obtained from patients and evaluation was performed at the end of each cycle. The primary endpoint were response rate and response duration. The secondary endpoints were safety, OS and PFS. IMWG index was utilized to analyze response criteria. SPSS 15.0 for windows® were used for statistical analysis.Enrolment started on February 2007, and a total of 60 patients have been included. Median age at randomization was 71 (56–84) years-old, and 52% of patients were female. Durie-Salmon stages were 12% II, 82% III and ISS stages were 47% II and 28% III. Fifty-one per cent of patients presented IgG monoclonal component. There were no significant differences comparing response > VGPR and treatment arms after three, six and nine cycles. However, the PFS is significant when compared CTD/MPT and TD arms (p=0.01). There was no difference in OS.This analysis showed that Thal combinations are effective in MM patient treatment. We have not observed different responses between the tree arms. The progression free survival is significant in favor of alkylating combination than thal+dexa (p=0.01). Toxicity was manageable and balanced between the tree different arms.We would like to thank Dr. Jesus San Miguel and Dra. Maria-Victoria Mateos who have collaborated in this study.No relevant conflicts of interest to declare.

Paiva: Jansen-Cillag: Honoraria; Celgene: Honoraria. Martinez:Janssen: Honoraria; Celgene: Honoraria. Maiolino:Centocor Ortho Biotech Research & Development: Research Funding.

Abstract 5117

Abstract 810FN2This icon denotes a clinically relevant abstract

Introduction: Autologous stem cell transplantation (ASCT) remains the mainstay of treatment of multiple myeloma (MM) in patients <65 years old. However, most patients relapse after ASCT suggesting that additional treatment is needed. The Brazilian Multiple Myeloma Group designed a study to evaluate the impact of thalidomide maintenance after ASCT. Methods: From October 2003 to July 2008, 212 untreated patients <70 years old were enrolled in a prospective randomized multicenter study. All patients signed an informed consent and the protocol was approved by the Ethical Committees of each center. The treatment consisted of 3 phases: induction with 3–5 cycles of VAD; high-dose cyclophosphamide (4g/m2) plus G-CSF for stem cell mobilization; (3) melphalan 200 mg/m2 and ASCT. On day +60 post ASCT patients were randomized to receive dexamethasone (40 mg/d × 4 days every 28 days) with (arm A) or without (arm B) thalidomide (200 mg daily) for 12 months or until disease progression. Results: The median age was 55 years (27–70), 52% were male, the median serum beta-2 microglobulin was 3.66 mg/dl, 33% were ISS stage 3, 36% were ISS stage 2 and 24% had deletion of chromosome 13. In July of 2008, 93 patients (44%) were randomized: 54 in arm A and 39 in arm B. Reasons for non-randomization were: treatment related deaths during phases 1–3 (n= 39), disease progression (n= 22), ineligible or refused ASCT (n= 7), SMD after ASCT (n= 1), protocol violation (n= 3), abandoned (n= 19), and still in phases 1–3 (n= 28). Clinical characteristics of each group were similar. The median follow-up from diagnosis was 15 months. PFS in arms A and B were 42% (95% confidence interval [CI] 22–62) and 25% (95% CI 5–45), p= 0.07. A multivariate analysis that included baseline serum beta-2-microglobulin and deletion of chromosome 13 showed that maintenance with thalidomide was significantly associated with better PFS (hazard ratio 2.43, 95% CI 1.10–5.35, p=0.03). Overall survival was 65% in arm A (95% CI 35–95) and 74% in arm B (95% CI 44–100), p= NS. Conclusions: A high proportion of MM in Brazil has advanced disease at diagnosis, and this explains the high number of patients who did not reach the maintenance phase. This study shows that the addition of thalidomide to dexamethasone improves PFS after a single ASCT.

Introduction: Autologous stem cell transplantation (ASCT) remains the mainstay of treatment of multiple myeloma (MM) in patients <65 years old. However, most patients relapse after ASCT suggesting that additional treatment is needed. The Brazilian Multiple Myeloma Group designed a study to evaluate the impact of thalidomide maintenance after ASCT.

Background: Bortezomib (VELCADE®) is a first-in-class, reversible proteasome inhibitor with activity in multiple myeloma (MM) and other malignancies. Bortezomib showed significant activity in previous phase 2 and 3 studies in patients (pts) with previously treated MM. This international multicenter open-label phase 3b study allowed expanded access to bortezomib therapy in pts with relapsed/refractory MM treated with ≥ 2 previous lines of therapy. Methods: Pts with MM were eligible if they had received ≥ 2 prior lines of therapy and required treatment due to relapsed or progressive disease. Pts with grade ≥ 2 peripheral neuropathy (PN) were excluded. Pts received 1.3 mg/m2 IV bolus bortezomib on days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles; dexamethasone (20 mg/d PO on the day of and day after bortezomib dose) could be added after cycle 2 for progressive disease or after cycle 4 for stable disease. Adverse events (AEs) were assessed beginning at the start of treatment and continuing until 30–42 days after treatment and were graded based on NCI-CTC version 2.0. Efficacy assessment was performed based on changes in disease burden as measured by monoclonal (M)-protein concentration in serum and urine every 2 cycles (6 weeks). Response was assessed using modified SWOG criteria: complete response (CR) was a 100% reduction in M-protein; very good partial response (VGPR), 75–99% reduction; partial response (PR), 50–74% reduction; minimal response (MR), 25–49% reduction; and stable disease, < 25% reduction. Increasing M-protein levels indicated progressive disease. Results: 624 pts in 93 centers from 21 countries received at least 1 dose of treatment and were evaluable for safety (55.3% male; median age 62.7 years). 68% of pts received 3–11 lines of previous therapy. Karnofsky performance status was ≤70 in 25.6% of pts; 141 pts (22.6%) were ≥ 70 years of age. Pts completed a median of 5 cycles of therapy (range 0–13); 39.3% of pts completed all 8 planned cycles. Grade 3/4 treatment-emergent (related and unrelated) AEs were reported in 430 pts (68.9%), with thrombocytopenia (29.2%), neutropenia (13.3%), and anemia (11.7%) the most common hematologic AEs. Grade 3/4 PN was reported in 8.2% of pts. Overall, 165 pts (26.4%) discontinued therapy due to treatment-related AEs. Best responses among evaluable pts (n = 593) included 12.0% CR, 23.1% VGPR, 19.1% PR, and 16.5% MR, for an overall response rate of 70.7%. Median time to first response was 42 days (range 7–125), and median time to best response was 63 days (range 7–235). Conclusions: Bortezomib 1.3 mg/m2 administered biweekly q3 weeks was well tolerated with manageable toxicities in pts with relapsed and/or refractory MM. Response rates with bortezomib were high, even in heavily pretreated pts, inducing > 25% CR/VGPR. This study confirms results from initial clinical trials in a broader population.

Aberrant methylation in promoter-associated CpG islands has been recognized as a major mechanism for silencing tumor suppressor genes in many malignant diseases. In multiple myeloma (MM), a limited number of studies of gene methylation have been reported, with conflicting results. We determined the methylation status of 9 suppressor tumor genes in 68 newly diagnosed MM patients by methylation specific PCR (MSP). Ten DNA of normal healthy donors were used as controls. The target genes chosen are involved in many cellular pathways as DNA repair (MGMT), cell cycle regulation (p15INK4b and p16INK4a), cell-cell adherence (E-cadherin), apoptosis (DAP-k and BNIP3), hormonal response (RARb and ER) and Jak/STAT3 signaling pathway (SHP1). An association between hypermethylation and loss of expression of these genes has been demonstrated. The correlation between methylation status and risk factors was assessed by Fisher exact test or Chi-square test (categorical variables) or Student’s t-test (continuous variables). Overall survival (OS) was estimated using the Kaplan-Meier method. Differences between survival curves were estimated by the log-rank test. Multivariate analysis of factors associated with OS was performed by Cox regression. With a median follow-up of 15.5 months, 16 patients died (23%). Healthy donor samples were negative for methylation in all 9 genes tested. Hypermethylation was detected in 50% of patients for E-cadherin, 43% for p16, 16% for p15, 15% for SHP1, 13% for ER and BNIP3, 12% for RARb, 6% for DAP-k, and 0% for MGMT. Overall, 54 patients (79%) presented at least one hypermethylated gene (1 in 19 patients, 2 in 17 patients, 3 in 12 patients, 4 in 5 patients, and 5 in 1 patient). By univariate analysis, hypermethylation of DAP-k (p<0.001) and RARb (p=0.01) genes, platelet counts <100,000/mm3 (p<0.001) and serum calcium >9.5 mg/dL (p=0.03) were identified as adverse prognostic features. The median OS of patients with hypermethylation in DAP-k (4 months) and RARb (34 months) were considerably lower compared to patients without aberrant methylation (median survival not reached, p<0.001 and p=0.01, respectively). Patients with hypermethylation of DAP-k were more likely to have a serum creatinine >2.0 mg/dL (p=0.006), serum calcium >9.5 mg/dL (p=0.05), and Durie-Salmon stage III (p=0.04). No correlation was observed between methylation status of any gene and the presence of chromosome 13 abnormalities, t(4;14)(p16;q32), or t(11;14)(q23;q32). By multivariate analysis, hypermethylation of DAP-k (odds ratio [OR] 5.56, 95% confidence interval [95% CI] 1.4 – 22, p=0.01) and platelet counts <100,000/mm3 (OR 4.13, 95% CI 1.32 – 12.8, p=0.01) were associated with poor prognosis. Our data suggest that hypermethylation of DAP-k is an independent prognostic factor in MM. The impact of these features in identifying a group of poor prognosis beyond the classical prognostic factors warrants a higher sample size and longer follow-up.

Aberrant methylation in promoter-associated CpG islands has been recognized as a major mechanism for silencing tumor suppressor genes in many malignant diseases. In multiple myeloma (MM), a limited number of studies of gene methylation have been reported, with conflicting results. We determined the methylation status of 9 suppressor tumor genes in 68 newly diagnosed MM patients by methylation specific PCR (MSP). Ten DNA of normal healthy donors were used as controls. The target genes chosen are involved in many cellular pathways as DNA repair (MGMT), cell cycle regulation (p15INK4band p16INK4a), cell-cell adherence (E-cadherin), apoptosis (DAP-kand BNIP3), hormonal response (RARband ER) and Jak/STAT3 signaling pathway (SHP1). An association between hypermethylation and loss of expression of these genes has been demonstrated. The correlation between methylation status and risk factors was assessed by Fisher exact test or Chi-square test (categorical variables) or Student's t-test (continuous variables). Overall survival (OS) was estimated using the Kaplan-Meier method. Differences between survival curves were estimated by the log-rank test. Multivariate analysis of factors associated with OS was performed by Cox regression. With a median follow-up of 15.5 months, 16 patients died (23%). Healthy donor samples were negative for methylation in all 9 genes tested. Hypermethylation was detected in 50% of patients for E-cadherin, 43% for p16, 16% for p15, 15% for SHP1, 13% for ERand BNIP3, 12% for RARb, 6% for DAP-k, and 0% for MGMT. Overall, 54 patients (79%) presented at least one hypermethylated gene (1 in 19 patients, 2 in 17 patients, 3 in 12 patients, 4 in 5 patients, and 5 in 1 patient). By univariate analysis, hypermethylation of DAP-k(p<0.001) and RARb(p=0.01) genes, platelet counts <100,000/mm3(p<0.001) and serum calcium >9.5 mg/dL (p=0.03) were identified as adverse prognostic features. The median OS of patients with hypermethylation in DAP-k(4 months) and RARb(34 months) were considerably lower compared to patients without aberrant methylation (median survival not reached, p<0.001 and p=0.01, respectively). Patients with hypermethylation of DAP-kwere more likely to have a serum creatinine >2.0 mg/dL (p=0.006), serum calcium >9.5 mg/dL (p=0.05), and Durie-Salmon stage III (p=0.04). No correlation was observed between methylation status of any gene and the presence of chromosome 13 abnormalities, t(4;14)(p16;q32), or t(11;14)(q23;q32). By multivariate analysis, hypermethylation of DAP-k(odds ratio [OR] 5.56, 95% confidence interval [95% CI] 1.4 – 22, p=0.01) and platelet counts <100,000/mm3(OR 4.13, 95% CI 1.32 – 12.8, p=0.01) were associated with poor prognosis. Our data suggest that hypermethylation of DAP-kis an independent prognostic factor in MM. The impact of these features in identifying a group of poor prognosis beyond the classical prognostic factors warrants a higher sample size and longer follow-up.

Background:Bortezomib (VELCADE®) is a first-in-class, reversible proteasome inhibitor with activity in multiple myeloma (MM) and other malignancies. Bortezomib showed significant activity in previous phase 2 and 3 studies in patients (pts) with previously treated MM. This international multicenter open-label phase 3b study allowed expanded access to bortezomib therapy in pts with relapsed/refractory MM treated with ≥ 2 previous lines of therapy.

Hematopoietic stem cell transplantation is a valid alternative as post-remission therapy in ALL. Our aim was analyzed retrospectively the clinical outcomes of 97 ALL patients with HLA identical sibling donors who underwent an allo PBSCT. Median age was 24 ys (2–45), advanced disease was present in 74%, conditioning without irradiation was 56%; GVHD prophylaxis with MTX/CsA was 91%; CD34+ median was 4.6X106/kg (1.2–24); the median follow-up for surviving patients was 22 months (1.6–93). Median day for neutrophils and platelets engraftment was 15 and 13, respectively; no TBI conditioning, no MTX/CsA, were associated significantly with faster neutrophils engraftment; no MTX/CsA with platelets. Cumulative incidence (CI) for ≥ 2 aGVHD was 45%, extensive cGVHD 50%; aGVHD in patients who received TBI conditioning was 34% (P=0.04). The estimates of OS and DFS at 92 months was 21% and 31%, respectively; OS for patients >36ys was 16% (P=0.04), for patients with aGVHD 11% (P=0.03); there was a trend towards better OS and DFS in patients with cGVHD (54%, 63%; P=0.07, P=0.06). CI for relapses was 60%; relapses for cGVHD patients were 36% (P= 0.05), and there was a trend towards higher relapses in advanced disease (66%, P=0.06). TRM was 64%; in those patients with aGVHD, 73% (P=0.008). In multivariate analyses no MTX/CsA was related with the speed of platelets engraftment (P=0.007); TBI conditioning was associated with less aGVHD and TRM (P=0.05, P=0.01); aGVHD had a negative impact on OS with higher TRM (P=0.02, P=0.02). Although not confirmed in the multivariate analyses, fewer relapses, and a trend towards better OS, and DFS were found in patients with extensive cGVHD. However, further follow up will be necessary to confirm these results.

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered standard of care for patients with Hodgkin's disease (HD) who relapse or progress after first-line chemotherapy. Recently, high-dose sequential chemotherapy (HDS) before ASCT has been evaluated, and phase II data suggest that it may improve the outcome without increasing significantly the toxicity. However, the lack of comparison between HDS and a more conservative strategy hampers any conclusion about the effectiveness of HDS. In this study, we compared in a non-randomized fashion, HDS (n=52) with a less-intensive chemotherapeutic regimen (non-HDS, n=60) followed by ASCT in patients with relapsed or refractory HD. Patients were treated at 2 Brazilian centers (HDS - UNICAMP; non-HDS - UFRJ). HDS consisted of cyclophosphamide (7 g/m2) followed by stem cell collection, methotrexate (8 g/m2) plus vincristine (1.4 mg/m2) and etoposide (2 g/m2), followed by BEAM and peripheral blood ASCT. Non-HDS patients received 2 cycles of DHAP, followed by cyclophosphamide (1,5 g/m2) followed by stem cell collection, followed by CBV and peripheral blood ASCT. There were more HDS patients with advanced disease (stage IV 40% vs. 13%, p=0.001), bulky disease (62% vs. 39%, p=0.02), and less patients in complete remission (CR) (6% vs. 18%, p=0.04). Toxic death before HSCT occurred in 5 patients in the HDS group and in none in the non-HDS group (p=0.02). Among 31 patients with progressive disease (PD) in the HDS group, 8 (25% remained in PD before ASCT, compared to 100% of 28 patients in the non-HDS group (p<0.001). The actuarial survival from HSCT was similar (58% in both groups, p=0.49), as was the disease free survival (64% in HDS vs. 80% in non-HDS, p=0.19). The outcome of patients from the HDS group who were in PD at the time of HSCT was significantly poorer than patients in CR or partial remission (actuarial survival zero vs. 77%, p<0.001). On the other hand, in the non-HDS group, the overall survival was not influenced by the disease status before ASCT (60% vs. 59%, p=0.77). Although HDS was associated with early deaths, it seemed to be beneficial to patients in PD. These results suggest that HDS could be preferably selected to patients with PD.

There are few treatment options for pts with multiply relapsed or refractory lymphoma. Allogeneic stem cell transplantation has historically been limited in this group by high transplant-related mortality (TRM) rates, and evidence for a clinically relevant graft-versus-lymphoma (GvL) effect has been limited. We evaluated reduced-intensity transplantation (RIT) in these pts with the aim of reducing TRM while exploiting the GvL effect. Between 12/00 and 02/05, 31 pts with an HLA-identical sibling were enrolled, 18 with non-Hodgkin (NHL) and 13 with Hodgkin (HL) lymphoma. Main characteristics were: median age = 33 years (range, 17–60); male gender = 20; histology = diffuse large B cell (9), T-cell anaplastic large cell (2), transformed-large cell (2), mantle cell, lymphoplasmacytic, T-peripheral, diffuse mixed large and small cell (1 each), and Hodgkin lymphoma (13). At study entry, 19 pts (36% NHL, 92% HL) had previously failed autologous transplantation (AT) and even patients who had not received high-dose chemotherapy had failed a median of 4+ lines of therapy. Five patients were in partial remission, 2 in untreated relapse post-AT and 24 had chemorefractory disease. Conditioning consisted of fludarabine (25 mg/m2x 5 d) and cyclophosphamide (60 mg/kg x 2 d). Twenty nine pts received peripheral blood and 2 received marrow stem cells. GVHD prophylaxis comprised cyclosporin and mini-methotrexate. Early death occurred in 3 pts from aspergillosis, pulmonary fibrosis and cardiac failure. All other patients engrafted, 1 with a progressively autologous pattern of chimerism. The overall incidende of grades II, III and IV acute GVHD was 50%, 10% and 7%, respectively. Chronic extensive GVHD occurred in 7/23 (30%) of evaluable pts. Eight pts (25%) died of progressive disease and 9 (29%) of non-relapse causes at a median of 2.5 (range, 1–12) months. Median overall and disease-free survival for all pts is 15.3 months and 7.9 months, respectively. Differences in overall and disease-free survival were not statistically significant between pts with NHL and HL (15.3 vs 25.2 months, p = 0.7; 5.9 vs 8.1, p = 0.44; respectively). Seven pts remain alive and disease-free (HL = 2/13 [15%]; NHL = 5/18 [27%]; p = 0.66) at median follow-up of 33.7 (range, 13.2 – 54.5) months. Allogeneic RIT is a reasonable therapeutic alternative for pts with relapsed NHL or HL, even those who have relapsed after AT. Mortality rates were acceptable for this heavily pretreated group of patients.

Introduction: The survival of patients with multiple myeloma varies from a few months to more than 10 years. This heterogeneity is related to the characteristics of the myeloma itself and of the host. The identification of the factors which influence the prognosis is very important to predict the result, assist in the choice of the treatment and adequately stratify the patients in clinical studies. Many prognostic factors have been identified in patients with multiple myeloma, such as anemia, renal failure, ß2 microglobulin, albumin and chromossomic alterations. Some authors have combined prognostic factors and proposed various systems of staging. However, none of them have yet substituted the Durie-Salmon staging system. Recently, the International Myeloma Working Group, with the objective of developing a simple and reliable staging system, which can be internationally applied to classify and stratify patients with multiple myeloma, identified 3 risk groups. This new system of staging, the “International Staging System” (ISS), consists of stage I: ß2 microglobulin < 3.5 mg/L plus albumin ≥ 3.5 g/dL (median survival: 62 months); stage II: neither I nor III (median 44 months); stage III: ß2 microglobulin > 5.5 mg/L (median 29 months). This study included sites in North America, Europe and Asia, but the sites in Latin America were not included. Objective: To validate the ISS in patients with multiple myeloma at Brazilian centers. Patients and Methods: Four hundred and eighty-seven patients with the diagnosis of multiple myeloma within the period of 1998 to 2004 at Santa Casa de São Paulo, Hospital Universitário Clementino Fraga Filho do Rio de Janeiro, Hospital das Clínicas de São Paulo, Hospital São Paulo, Hospital das Clínicas de Ribeirão Preto, HEMOPE, Hospital Prof. Edgar Santos de Salvador and Hospital de Clínicas de Porto Alegre, with available data on albumin and ß2 microglobulin, were stratified according to the ISS. A total of 339 patients received standard therapy and 148 received high-dose therapy as initial therapy. The survival was estimated using the Kaplan-Meier method with differences in survival examined using the logrank test. Results: The median age of the patients was 60 years, 52% male and 48% female. In Stage I (n=104), the global median survival was not reached, the survival at 60 months was 60%, in stage II (n=264), the global median survival was 61 months and in stage III (n=119), 19 months (p<0.001). Conclusion: The new system of staging for multiple myeloma (ISS) is simple, based on variables easy to be applied and was possible to be validated in patients with multiple myeloma in Brazilian centers.

Hematopoietic stem cell transplantation is a valid alternative as post-remission therapy in ALL. Our aim was analyzed retrospectively the clinical outcomes of 97 ALL patients with HLA identical sibling donors who underwent an allo PBSCT. Median age was 24 ys (2–45), advanced disease was present in 74%, conditioning without irradiation was 56%; GVHD prophylaxis with MTX/CsA was 91%; CD34+median was 4.6X106/kg (1.2–24); the median follow-up for surviving patients was 22 months (1.6–93). Median day for neutrophils and platelets engraftment was 15 and 13, respectively; no TBI conditioning, no MTX/CsA, were associated significantly with faster neutrophils engraftment; no MTX/CsA with platelets. Cumulative incidence (CI) for ≥ 2 aGVHD was 45%, extensive cGVHD 50%; aGVHD in patients who received TBI conditioning was 34% (P=0.04). The estimates of OS and DFS at 92 months was 21% and 31%, respectively; OS for patients >36ys was 16% (P=0.04), for patients with aGVHD 11% (P=0.03); there was a trend towards better OS and DFS in patients with cGVHD (54%, 63%; P=0.07, P=0.06). CI for relapses was 60%; relapses for cGVHD patients were 36% (P= 0.05), and there was a trend towards higher relapses in advanced disease (66%, P=0.06). TRM was 64%; in those patients with aGVHD, 73% (P=0.008). In multivariate analyses no MTX/CsA was related with the speed of platelets engraftment (P=0.007); TBI conditioning was associated with less aGVHD and TRM (P=0.05, P=0.01); aGVHD had a negative impact on OS with higher TRM (P=0.02, P=0.02). Although not confirmed in the multivariate analyses, fewer relapses, and a trend towards better OS, and DFS were found in patients with extensive cGVHD. However, further follow up will be necessary to confirm these results.

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is considered standard of care for patients with Hodgkin’s disease (HD) who relapse or progress after first-line chemotherapy. Recently, high-dose sequential chemotherapy (HDS) before ASCT has been evaluated, and phase II data suggest that it may improve the outcome without increasing significantly the toxicity. However, the lack of comparison between HDS and a more conservative strategy hampers any conclusion about the effectiveness of HDS. In this study, we compared in a non-randomized fashion, HDS (n=52) with a less-intensive chemotherapeutic regimen (non-HDS, n=60) followed by ASCT in patients with relapsed or refractory HD. Patients were treated at 2 Brazilian centers (HDS - UNICAMP; non-HDS - UFRJ). HDS consisted of cyclophosphamide (7 g/m2) followed by stem cell collection, methotrexate (8 g/m2) plus vincristine (1.4 mg/m2) and etoposide (2 g/m2), followed by BEAM and peripheral blood ASCT. Non-HDS patients received 2 cycles of DHAP, followed by cyclophosphamide (1,5 g/m2) followed by stem cell collection, followed by CBV and peripheral blood ASCT. There were more HDS patients with advanced disease (stage IV 40% vs. 13%, p=0.001), bulky disease (62% vs. 39%, p=0.02), and less patients in complete remission (CR) (6% vs. 18%, p=0.04). Toxic death before HSCT occurred in 5 patients in the HDS group and in none in the non-HDS group (p=0.02). Among 31 patients with progressive disease (PD) in the HDS group, 8 (25% remained in PD before ASCT, compared to 100% of 28 patients in the non-HDS group (p<0.001). The actuarial survival from HSCT was similar (58% in both groups, p=0.49), as was the disease free survival (64% in HDS vs. 80% in non-HDS, p=0.19). The outcome of patients from the HDS group who were in PD at the time of HSCT was significantly poorer than patients in CR or partial remission (actuarial survival zero vs. 77%, p<0.001). On the other hand, in the non-HDS group, the overall survival was not influenced by the disease status before ASCT (60% vs. 59%, p=0.77). Although HDS was associated with early deaths, it seemed to be beneficial to patients in PD. These results suggest that HDS could be preferably selected to patients with PD.

There are few treatment options for pts with multiply relapsed or refractory lymphoma. Allogeneic stem cell transplantation has historically been limited in this group by high transplant-related mortality (TRM) rates, and evidence for a clinically relevant graft-versus-lymphoma (GvL) effect has been limited. We evaluated reduced-intensity transplantation (RIT) in these pts with the aim of reducing TRM while exploiting the GvL effect. Between 12/00 and 02/05, 31 pts with an HLA-identical sibling were enrolled, 18 with non-Hodgkin (NHL) and 13 with Hodgkin (HL) lymphoma. Main characteristics were: median age = 33 years (range, 17–60); male gender = 20; histology = diffuse large B cell (9), T-cell anaplastic large cell (2), transformed-large cell (2), mantle cell, lymphoplasmacytic, T-peripheral, diffuse mixed large and small cell (1 each), and Hodgkin lymphoma (13). At study entry, 19 pts (36% NHL, 92% HL) had previously failed autologous transplantation (AT) and even patients who had not received high-dose chemotherapy had failed a median of 4+ lines of therapy. Five patients were in partial remission, 2 in untreated relapse post-AT and 24 had chemorefractory disease. Conditioning consisted of fludarabine (25 mg/m2 x 5 d) and cyclophosphamide (60 mg/kg x 2 d). Twenty nine pts received peripheral blood and 2 received marrow stem cells. GVHD prophylaxis comprised cyclosporin and mini-methotrexate. Early death occurred in 3 pts from aspergillosis, pulmonary fibrosis and cardiac failure. All other patients engrafted, 1 with a progressively autologous pattern of chimerism. The overall incidende of grades II, III and IV acute GVHD was 50%, 10% and 7%, respectively. Chronic extensive GVHD occurred in 7/23 (30%) of evaluable pts. Eight pts (25%) died of progressive disease and 9 (29%) of non-relapse causes at a median of 2.5 (range, 1–12) months. Median overall and disease-free survival for all pts is 15.3 months and 7.9 months, respectively. Differences in overall and disease-free survival were not statistically significant between pts with NHL and HL (15.3 vs 25.2 months, p = 0.7; 5.9 vs 8.1, p = 0.44; respectively). Seven pts remain alive and disease-free (HL = 2/13 [15%]; NHL = 5/18 [27%]; p = 0.66) at median follow-up of 33.7 (range, 13.2 – 54.5) months. Allogeneic RIT is a reasonable therapeutic alternative for pts with relapsed NHL or HL, even those who have relapsed after AT. Mortality rates were acceptable for this heavily pretreated group of patients.

Introduction: The survival of patients with multiple myeloma varies from a few months to more than 10 years. This heterogeneity is related to the characteristics of the myeloma itself and of the host. The identification of the factors which influence the prognosis is very important to predict the result, assist in the choice of the treatment and adequately stratify the patients in clinical studies. Many prognostic factors have been identified in patients with multiple myeloma, such as anemia, renal failure, ß2microglobulin, albumin and chromossomic alterations. Some authors have combined prognostic factors and proposed various systems of staging. However, none of them have yet substituted the Durie-Salmon staging system. Recently, the International Myeloma Working Group, with the objective of developing a simple and reliable staging system, which can be internationally applied to classify and stratify patients with multiple myeloma, identified 3 risk groups. This new system of staging, the “International Staging System” (ISS), consists of stage I: ß2microglobulin < 3.5 mg/L plus albumin ≥ 3.5 g/dL (median survival: 62 months); stage II: neither I nor III (median 44 months); stage III: ß2microglobulin > 5.5 mg/L (median 29 months). This study included sites in North America, Europe and Asia, but the sites in Latin America were not included.

This is a retrospective analysis of 1084 patients who received an allogeneic HSCT in 10 Brazilian Centers, from February 1983 to March 2003, aiming to validate the EBMT risk score. Data from transplanted patients and donors regarding patients age, disease stage at transplantation, HLA full-match sibling donor or full-match unrelated donors, donor-recipient gender match and the interval from diagnosis to transplantation, were used as variables to calculate the EBMT risk score. This score was analyzed using Cox Proportional Hazards Model. The OS, DFS, TRM and relapse were analyzed using Kaplan-Meier and cumulative incidence, whenever appropriate. In all there were 647 (60%) males and 437 (40%) females, the median age was 32 years old (range 1 – 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1025 (95%) received HLA full-match sibling transplant and only 59 (5%) received an unrelated transplant. Female donor to male recipient occurred in 283 (26%) transplants. The interval from diagnosis to transplantation was less than 12 months in 223 (21%) cases and greater in 861 (79%). The OS, DFS, TRM and, relapse were 49%, 50%, 45%, 25%, respectively. The risk score 0–1 occurred in 179 (17%), score 2 in 397 (37%), score 3 in 345 (32%), score 4 in 135 (12%), and score 5–6 in 28 (2%). The risk scores 0–1 and 2 did not show any difference in terms of OS (58% and 55%, respectively) but they were significantly better than scores 3 or more (score 3 – 44%, 4 – 36 % and, 5-6 - 27%, respectively) (P<0.001). DFS and TRM beyond score 3 were 46%, 49%, respectively and the relapse rate beyond score 5–6 was 77%. Disease status had a negative impact on all outcomes (OS, DFS, TRM, and relapse). OS for female donor - male recipient was 40% compared to 52% for the other patients (P=0.004). DFS and TRM were significant for disease phase and female donor-male recipient (P<0.001 and P<0.003, respectively). In our experience, age and interval from diagnosis and transplant did not show any difference in terms of OS, DFS, TRM, and relapse rate. Our results confirm the usefulness of the EBMT risk score for point-decision in the Imatinib era.

This is a retrospective analysis of 1084 patients who received an allogeneic HSCT in 10 Brazilian Centers, from February 1983 to March 2003, aiming to validate the EBMT risk score. Data from transplanted patients and donors regarding patients age, disease stage at transplantation, HLA full-match sibling donor or full-match unrelated donors, donor-recipient gender match and the interval from diagnosis to transplantation, were used as variables to calculate the EBMT risk score. This score was analyzed using Cox Proportional Hazards Model. The OS, DFS, TRM and relapse were analyzed using Kaplan-Meier and cumulative incidence, whenever appropriate. In all there were 647 (60%) males and 437 (40%) females, the median age was 32 years old (range 1 – 59); 898 (83%) were in chronic phase, 146 (13%) were in accelerated phase and 40 (4%) were in blast crisis; 151 (14%) were younger than 20 years old, 620 (57%) were between 20 and 40 and 313 (29%) were older than 40; 1025 (95%) received HLA full-match sibling transplant and only 59 (5%) received an unrelated transplant. Female donor to male recipient occurred in 283 (26%) transplants. The interval from diagnosis to transplantation was less than 12 months in 223 (21%) cases and greater in 861 (79%). The OS, DFS, TRM and, relapse were 49%, 50%, 45%, 25%, respectively. The risk score 0–1 occurred in 179 (17%), score 2 in 397 (37%), score 3 in 345 (32%), score 4 in 135 (12%), and score 5–6 in 28 (2%). The risk scores 0–1 and 2 did not show any difference in terms of OS (58% and 55%, respectively) but they were significantly better than scores 3 or more (score 3 – 44%, 4 – 36 % and, 5-6 - 27%, respectively) (P<0.001). DFS and TRM beyond score 3 were 46%, 49%, respectively and the relapse rate beyond score 5–6 was 77%. Disease status had a negative impact on all outcomes (OS, DFS, TRM, and relapse). OS for female donor - male recipient was 40% compared to 52% for the other patients (P=0.004). DFS and TRM were significant for disease phase and female donor-male recipient (P<0.001 and P<0.003, respectively). In our experience, age and interval from diagnosis and transplant did not show any difference in terms of OS, DFS, TRM, and relapse rate. Our results confirm the usefulness of the EBMT risk score for point-decision in the Imatinib era.

Uncertainty still exists with the effects of allogeneic PBSCT on the clinical outcomes of patients with hematological malignancies. Our aim was analyzed retrospectively the clinical outcomes of 483 patients who underwent an allo PBSCT in 9 Brazilians centers from May 1994 to February 2004. The analyzes included patients with hematological malignancies who underwent PBSCT from HLA identical siblings donors treated with G-CSF at a dose of 10mgr/kg/day, 5 days. Median age was 34ys old (2–57), advanced disease was present in 58%, conditioning without irradiation was 85%; GVHD prophylaxis with MTX/CsA was 91%; CD34+ median was 4.7X106/kg (0.51–71.6); the median follow-up for surviving patients was 797 days (8–3420); median day for neutrophils and platelets engraftment was 15 and 14, respectively; cumulative incidence (CI) for ³ 2 aGVHD was 38%; extensive cGVHD 63%; CI for transplant relate mortality (TRM) 59%; CI for relapse 37%; the estimates of OS and DFS at 9 ys are 33% and 42, respectively. The following factors were significantly associated with better outcomes for engraftment, aGVHD, cGVHD, OS, DFS, relapse, and TRM in univariate analyzes, respectively: neutrophils and platelets engraftment: CD34+ cell dose > 2.8X106/kg, GVHD prophylaxis other than MTX/CsA, and sex match other than female donor for male recipient; aGVHD: age<43ys old, and CD34 dose > 4.7X106/kg; cGVHD: age < 25ys, sex match other than female donor for male recipient, advanced disease and CD3+ dose < 170X106/kg; OS: early disease; DFS: early disease, CD34+ dose > 4.7X106/kg; relapse: age> 25ys, CD34+ cell dose > 2.8X106/kg, and early disease; TRM: early disease. All the results remained significant in multivariate analyzes, but CD34+ dose and platelet engraftment; age and CD34+ dose in aGVHD; age and CD3+ in cGVHD, and age in relapse. In our experience, sex match, CD34+ dose, GVHD prophylaxis may influence the engrafment, and sex match and disease phase the cGVHD. Furthermore, advanced disease had a negative impact on OS and TRM;. CD34+ higher dose and early disease were associated with better DFS and lower relapse.

Uncertainty still exists with the effects of allogeneic PBSCT on the clinical outcomes of patients with hematological malignancies. Our aim was analyzed retrospectively the clinical outcomes of 483 patients who underwent an allo PBSCT in 9 Brazilians centers from May 1994 to February 2004. The analyzes included patients with hematological malignancies who underwent PBSCT from HLA identical siblings donors treated with G-CSF at a dose of 10mgr/kg/day, 5 days. Median age was 34ys old (2–57), advanced disease was present in 58%, conditioning without irradiation was 85%; GVHD prophylaxis with MTX/CsA was 91%; CD34+ median was 4.7X106/kg (0.51–71.6); the median follow-up for surviving patients was 797 days (8–3420); median day for neutrophils and platelets engraftment was 15 and 14, respectively; cumulative incidence (CI) for ³ 2 aGVHD was 38%; extensive cGVHD 63%; CI for transplant relate mortality (TRM) 59%; CI for relapse 37%; the estimates of OS and DFS at 9 ys are 33% and 42, respectively. The following factors were significantly associated with better outcomes for engraftment, aGVHD, cGVHD, OS, DFS, relapse, and TRM in univariate analyzes, respectively: neutrophils and platelets engraftment: CD34+ cell dose > 2.8X106/kg, GVHD prophylaxis other than MTX/CsA, and sex match other than female donor for male recipient; aGVHD: age<43ys old, and CD34 dose > 4.7X106/kg; cGVHD: age < 25ys, sex match other than female donor for male recipient, advanced disease and CD3+ dose < 170X106/kg; OS: early disease; DFS: early disease, CD34+ dose > 4.7X106/kg; relapse: age> 25ys, CD34+ cell dose > 2.8X106/kg, and early disease; TRM: early disease. All the results remained significant in multivariate analyzes, but CD34+ dose and platelet engraftment; age and CD34+ dose in aGVHD; age and CD3+ in cGVHD, and age in relapse. In our experience, sex match, CD34+ dose, GVHD prophylaxis may influence the engrafment, and sex match and disease phase the cGVHD. Furthermore, advanced disease had a negative impact on OS and TRM;. CD34+ higher dose and early disease were associated with better DFS and lower relapse.