ALBERT

Description: Stage of the disease at transplant is critical for outcome after unrelated donor umbilical cord blood transplantation (UD-UCBT). The results of UD-UCBT in adults transplanted early in the course of their disease are unclear. Thus, UD-UCBT remains as the last resort for most patients. The major aim of this report was to study the outcome of a series of adult patients with hematologic malignancies undergoing UD-UCBT early in the course of their disease in a single institution. From May 1997 to May 2004, 40 patients in early disease stages underwent UD-UCBT. All patients received thiotepa, busulfan (orally in 29, intravenously in 11), cyclophosphamide, and antithymocyte globulin (Lymphoglobulin in 24 and Thymoglobulin in 16) as conditioning, cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis, and filgrastim to fasten engraftment. Diagnosis were chronic myeloid leukemia in chronic phase in 14 cases, high-risk acute lymphoblastic leukemia in 14 (12 in CR1, 1 in CR2, and 1 in CR3), high-risk acute myeloblastic leukemia in 8 (7 in CR1 and 1 in CR2), and high-risk myelodysplastic syndrome in 4 (3 untreated and 1 in CR1). Median age was 27 years (range, 16–46). The degree of HLA match (HLA-A and -B by serology and -DRB1 by high-resolution DNA typing) was 6/6 in 2 (5%), 5/6 in 18 (45%), and 4/6 in 20 cases (50%). The median number of nucleated and CD34+ cells infused was 1.8 x 107/kg (range, 0.9–4) and 0.8 x 105/kg (range, 0.1–5.7) respectively. Median time to PMN above 0.5 x 109/L and to platelets above 20 x 109/L was 22 days (range, 13–44) and 69 days (range, 32–188), and the cumulative incidence of myeloid and platelet engraftment was 90% (95% CI, 81–99%) and 70% (95% CI, 57–86%), respectively. Time to myeloid engraftment showed a direct relationship with the number of CFU-GM and CD34 cells cryopreserved (P = .02 and .01 respectively) and infused (P = .0001 and .0004 respectively). Platelet engraftment was faster in patients receiving grafts with a higher number of CFU-GM (P = .005) and CD34+ cells (P = .04), in those receiving Thymoglobulin (P = .02) and in those not developing acute GVHD above grade II (P = .04). Eight patients (20%) developed acute GVHD above grade II, and 9 of 25 patients at risk had extensive chronic GVHD. Patients receiving Thymoglobulin had a lower risk of acute GVHD (P = .0003). With a median follow-up of 33 months (range, 3–87), the probability of disease-free survival (DFS) at 3 years was 48% (95% CI, 30–66%) and was related directly to age (P = .004) and inversely to the development of acute GVHD above grade II (P = .004). The probability of DFS at 3 years was 66 % for patients younger than 31 years and 54% for those not developing acute GVHD above grade II. Cell dose, degree of HLA mismatch, and diagnosis did not clearly influence DFS. These results compare to those obtained after matched unrelated donor bone marrow transplantation, and suggest that UD-UCBT is a reasonable first-line option for adults with hematologic malignancies requiring transplantation and lacking a HLA-matched sibling donor.

Description: Background: The trombopoietin receptor agonists (TRAs) romiplostim and eltrombopag are effective and safe in the treatment of chronic immune thrombocytopenia (ITP). However, when no response is achieved or when adverse events occur with one TRA the value of the sequential use of romiplostim and eltrombopag has not been clearly established. Here we have evaluated the efficacy and tolerance of using eltrombopag after romiplostim in ITP. Methods: Fifty-one primary ITP patients (aged 18 years or more) who had been sequentially treated first with romiplostim and then with eltrombopag in the Spanish Eltrombopag Registry were retrospectively evaluated. In accordance with the usual standards, complete response was defined as a platelet count of 100x109/L and a response as a platelet count of 30x109/L or a count of at least twice the initial (pre-treatment) value. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee. Results: The median age of our cohort was 49 [range, 18–83] years. There were 32 women and 19 men. According to the standard definition, patients were allocated to newly diagnosed (n=2), persistent (n=5) and chronic (n=44) ITP groups. The median number of therapies prior to administration of eltrombopag was 4 [range, 2–9], including splenectomy (39%), rituximab (33%) and romiplostim (100%). The median duration of romiplostim use before switching to eltrombopag was 12 (IQR 5–21) months. The reasons for switching from the romiplostim to eltrombopag were: lack of efficacy of romiplostim (n=25), patient's preference (n=16), platelet-count fluctuation (n=6), and side-effects (n=4). The initial response rate to eltrombopag was 41/51 (80.5%), including 67% (n=34) of cases with complete remission. After a median follow-up of 13 months with eltrombopag, 39 patients maintained their response. When eltrombopag was used for patients who were refractory to the maximum romiplostim dose the initial response rate of eltrombopag was 25%. However, 83% of patients who relapsed after their initial response to romiplostim responded to eltrombopag. Sixteen romiplostim responders requested their physicians to switch them to eltrombopag because they preferred an oral drug. The efficacy was maintained after switching in all 16 patients. In the platelet-count fluctuation group, the initial response rate was also 100%. All 4 patients who were switched to eltrombopag because they experienced side-effects of romiplostim achieved complete remission with eltrombopag and their adverse events were resolved. 16 / 51 (33%) patients experienced one or more adverse event during treatment with eltrombopag. The frequency of grade 3–4 adverse events during treatment with eltrombopag was 9.8%. Conclusion: The use of eltrombopag after romiplostim for treating ITP is effective and safe. The reason for discontinuing romiplostim was associated with the response to eltrombopag. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: There is scarce information concerning incidence and risk factors for central nervous system (CNS) relapse in adult patients with acute myeloid leukemia (AML). In acute lymphoblastic leukemia CNS relapse occurs in up to 30% of patients without prophylactic intrathecal chemotherapy (ITC). This has lead to establish its prophylactic use during induction and post-remission phase. Due to the lack of information about incidence of CNS relapse in adult patients with AML, the usefulness of ITC prophylaxis is not clear. Objectives: Analyze incidence and risk factors for CNS relapse in a large cohort of adult patients with newly diagnosed AML. Material y methods: Between 1976 y 2005, 747 adult patients (median 54 years, range 16–81) were diagnosed of de novo AML in our institution. All of them received induction with intensive chemotherapy. Prophylactic ITC was not administered, and cerebrospinal fluid was analyzed only if CNS infiltration was suspected. We analyzed the incidence and risk factors for CNS relapse in patients who reached a complete remission. To calculate the Kaplan-Meier estimates of event-free survival (EFS) we considered as an event the first relapse in CNS, censoring patients at the moment of death or at first relapse in a site different than CNS. Results: 432 patients (58%) obtained complete remission. Between 1976 and 1989 (period 1) 12 of 136 patients (9%) were submitted to autologous or allogeneic stem-cell transplantation (SCT), whereas 129 of 296 (44%) received SCT between 1990 and 2005 (period 2). Overall, 8 of 432 patients (2%) had a CNS relapse, 3 isolated in CNS and 5 in bone marrow plus CNS. Of them, only 1 presented CNS infiltration at diagnosis. In univariate analysis, CNS relapse was associated with high LDH (3% vs 0%, p=0.06), lisozyme 〉30 (8% vs 1%, p=0.06), FAB M4–M5 (5% vs 1%, p=0.04) and period 1 (5% vs 0.3%, p

Description: Abstract 1978 Background: Autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, in the rituximab era, patients with persistent disease receiving ASCT have a very poor outcome. Recent studies including radioimmunotherapy as part of the conditioning treatment suggest an improved outcome for this group of patients. Methods: We have evaluated, in a prospective phase 2 study, the safety and efficacy of yttriumm-90-ibritumomab tiuxetan (Zevalin) combined with standard BEAM in refractory DLBCL patients. Thirty patients with induction failure (primary refractory; n=18) or refractory to salvage immunochemotherapy at relapse (n=12) were included in the study. Patients' response was evaluated with PET-CT according to 2007 Cheson's revised response criteria. Results: Patients with a median age of 53 years (range, 25–67) received Zevalin at a fixed dose of 0.4mCi/kg (maximum dose 32 mCi) 14 days prior to standard BEAM. Histology included de novo DLBCL (22) and transformed DLBCL (8). Patients received a median of 3 (range, 2–6) prior therapies before ASCT. All patients had active disease at the time of ASCT, with 25 patients considered to be chemorefractory to the last treatment. Median CD34+ cell dose infused was 3.9 × 106/kg (range, 2–18.3). All patients engrafted. Median time to neutrophil recovery (〉500/μl) was 11 days (9–21), and to platelet recovery (〉20.000/μl) was 13 days (11–35). Overall response at day +100 was 70% (95% CI, 53.6–86.4) with 60% (95% CI, 42.5–77.5) complete responses. Eleven patients have died. One due to a cerebral hemorrhage before ASCT and 1 due to sepsis immediately post-transplant. Seven patients died of disease progression, and 2 patients died due to late complications: bacterial sepsis and secondary acute leukemia. One patient developed a myelodysplastic syndrome (refractory anemia with excess blasts-2) 33 months after TASP, while being in CR of its lymphoma. After a median follow-up of 22.7 months for alive patients (range, 12.2–39.0), 2-year overall and progression-free survival is 65% (95% CI, 47.8–82.8) and 63% (95% CI, 45.5–80.4), respectively. Conclusion: ASCT with conditioning including Zevalin radioimmunotheray plus BEAM is safe, and results in a very high response rate with promising survival in this very poor prognosis group of refractory DLBCL patients. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1382 The effectiveness of rituximab maintenance in the treatment of CLL has been investigated in a phase II clinical trial that includes two treatment parts. First, patients were given R-FCM up to 6 cycles as induction therapy, achieving an overall response rate of 93% and 46% of CR with negative minimal residual disease (MRD) (Bosch et al. JCO, etc). Second, three months after concluding R-FCM, patients having achieved CR or PR receive rituximab maintenance (375 mg/m2) every three months for two years (up to 8 cycles). We present here the preliminary results of the second part of the study, namely the efficacy of rituximab maintenance. Evaluation of response was performed three months after the last cycle of maintenance and included bone marrow (BM) examination, MRD assessment in peripheral blood and BM by four-color flow cytometry. Patients in whom rituximab maintenance was prematurely interrupted due to toxicity were considered as failures. Fifty-six patients (median age 60 years, 70% female) responding to R-FCM were evaluable for response to rituximab maintenance. Median number of cycles of maintenance given was 8 (range, 3 to 8), 77% of patients completed the entire planned treatment, whereas 91% received 6 or more cycles. Treatment was delayed due to insufficient hematological recovery in 12 cycles (2.7%). Toxicity was mainly hematological, with neutropenia being observed in 31.8% of cycles (Grade 3&4 in 8.9%), thrombocytopenia in 3.4% and anemia in 3.9%. Hypogammaglobulinemia occurred in 38% of patients (low levels of IgA in 50%, IgG in 34%, and IgM in 60%). Eight patients, three of them with hypogammaglobulinemia, experienced grade 3&4 infectious episodes (4 pneumonia, 2 gastrointestinal, 1 myositis, and 1 cerebral abscess). Herpes virus (I/VZ) reactivation was observed in 8 patients. Two patients died due to multifocal leukoencephalopathy and hemophagocytic syndrome, respectively. After rituximab maintenance, 44.6% of patients were in CR MRD negative, 41% in CR, 3.6% in PR, and 10.7% failed to treatment. Failures were due to disease progression (two patients), development of severe neutropenia (two patients), and death (two patients). Among 28 patients that were in CR MRD (-) at the onset of the maintenance part, 19 held the MRD negative status at the end of maintenance, 5 (18%) turned negative into positive MRD (probability of conversion, 40% at 30 months), whereas 4 failed to treatment (2 neutropenia, 1 progression, 1 death). Moreover, 5 of 24 patients (22%) in CR MRD(+) after R-FCM became MRD negative after rituximab maintenance, 17 maintained the CR, one patient achieved a PR, and one patient progressed under maintenance (Table 1). In conclusion, rituximab maintenance after chemoimmunotherapy seems to prolong duration of response and, in some cases, improves the quality of response towards a CR with negative MRD. Maintenance with rituximab had the major benefit in patients in CR with positive MRD. The exact role and the best dosage and treatment schedule of rituximab as maintenance therapy in CLL should be now investigated in randomized clinical trials. Disclosures: Bosch: Hoffman La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Rituximab is currently not approved as maintenance therapy for patients with chronic lymphocytic leukemia. Garcia-Marco:ROCHE: Consultancy, Honoraria, Research Funding.

Description: Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by specific morphological and clinical features. However, its relative incidence among patients with AML is not yet established. Objectives: To define the relative incidence of APL in a large series of patients diagnosed with AML in a single institution and to identify the clinical-biological features characterizing the APL patients within the target population of AML. Methods: From 1976 to 2007, 1205 patients (median age 56 years, range 15–98) were consecutively diagnosed with AML in our institution. One hundred patients (8%) were considered AML secondary to solid neoplasia or chemotherapy, while 143 (12%) were secondary to myelodysplastic or myeloprolypherative syndromes (MDS/MPCS). The APL diagnosis was achieved through cytological studies supported by cytogenetics, and since 1995 by molecular techniques. Inmunophenotype analysis, using flow cytometry or inmunohistochemistry, was available in 808 (67%) patients. Positivity was defined as more than 20% blasts expressing a specific antigen. Results: Overall, 170 patients (14%) were diagnosed of APL. Of them, 43 (25%) were classified as M3 variant. The relative incidence of APL within AML secondary to solid neoplasia or chemotherapy and de novo AML was 13% y 16%, respectively (p=ns). In contrast, the relative incidence of APL within AML secondary to MDS/MPCS was 0.7% (p

Description: BACKGROUND: Adult patients with high-risk ALL can benefit from allogeneic stem cell transplantation but most lack a suitable sibling or unrelated adult donor. Umbilical cord blood has emerged as an alternative source for stem cell transplantation. OBJECTIVES: The aim of the present study was to evaluate toxicity and efficacy of UD-UCBT for the treatment of high-risk ALL in adults as well as to identify by multivariate analysis factors affecting transplant outcome. PATIENTS AND METHODS: Thirty-seven consecutive patients (23 males, 14 females) with median age 26 yr (range, 15–47) who underwent UD-UCBT at a single institution from 1999 until 2006 were analyzed. Primary high-risk feature was Philadelphia-positive ALL (12), MLL rearrangement (3), primary refractory disease (3), salvage treatment for patients in second complete remission (CR2, 4) or beyond CR2 (6), and slow response to initial therapy or 2 cycles to achieve CR (9). Conditioning regimen consisted of thiotepa, busulfan (oral, 13; IV, 24), cyclophosphamide (24) or fludarabine (13), and anti-thimocyte globulin. Cyclosporine and prednisone were used for graft-versus-host disease (GVHD) prophylaxis. Most patients (95%) received an HLA-mismatched cord blood unit with 1 (35%) or 2 (60%) HLA disparities. At infusion, the median number of nucleated cells and CD34+ cells was 2.4 × 107/kg and 1.3 × 105/kg, respectively. RESULTS: Cumulative incidence (CI) of myeloid and platelet engraftment was 92% and 76% at a median time of 21 and 63 days respectively. CI of GVHD acute grades II-IV, III-IV and chronic extensive was 29%, 19% and 19% respectively. Transplant-related mortality at 180 days was 29% and was significantly increased in patients developing severe acute GVHD (96% vs 19%; p 〈 0.001). With a median follow-up of 23 months (range, 7–88), CI of relapse was 34% at 3 years and was higher in patients beyond CR1 (63% vs 28%; p 〈 0.001). 3-year event-free survival (EFS) and overall survival (OS) were 33% and 37%, respectively. Patients in CR1/2 had better EFS (41% vs 14%; p = 0.04) and OS (50% vs 14%; p = 0.04) while those who developed severe acute GVHD had a worse EFS (42% vs 0%; p = 0.004) and OS (49% vs 0%; p = 0.004). CONCLUSIONS: These results show that UD-CBT is a curative alternative for a significant number of patients with high-risk ALL. This option should be offered to patients early in the course of their disease to improve outcomes.

Description: Background: survival of young patients with high IPI DLBCL treated with RCHOP chemotherapy needs to be improved. In this poor risk population the combination of RCHOP with new drugs is an attractive approach, along with performing an early evaluation with PET/CT after 2 to 4 cycles and change induction therapy if a complete response is not achieved. Bortezomib has been combined with RCHOP [1]. We present preliminary data of patients treated in a clinical trial comparing 6 cycles of RCHOP vs 6 cycles of BRCAP, a modified RCHOP regimen changing vincristine by bortezomib at a dose of 1.3 mg/m2 sc days 1, 8, and 15 of every 21 days cycle (NCT01848132). Methods: patients younger than 70 yrs diagnosed of DLBCL with aIPI 2-3 or aIPI 1 with elevated beta2microglobulin were eligible. The main objective was to evaluate the proportion of patients who survives free of event at 2 years. Central pathology review was performed in all cases, and samples were classified as GC vs non-GC subtypes by IHC (Hans algorithm). PET/CTs were performed at diagnosis, after 2, 4 and 6 cycles (PET2, PET4 , and PET6), and were reviewed by at least 3 experts of a central panel at real time. Response was analyzed following the visual method with the Deauville scale, and for PET2 and PET4 the semiquantitative method was used. Patients with persistent disease after 4 cycles were considered a failure of therapy and were dropped out from the trial. Results: data from the first 76 patients were analyzed. Diagnosis of DLBCL was confirmed in all except 3 pts, 36 pts were treated in the experimental arm and 37 in the control arm. Median age was 58.2 yo (range 23-70), 37 (50.7%) were males. Characteristics at diagnosis were: non-GC subtype 18/46 (39.1%), C-myc expression 35/43 (81.4%), bcl2 expression 43/49 (87.7%), double expression cmyc/bcl2 30/42 (71%), stage III-IV 64 (87.6%), ≥2 extranodal locations 27 (42.2%), ECOG 2-3 24 (33%), elevated LDH 43 (62.3%), elevated beta 2 microglobulin 47 (75.8%), aIPI 2: 42 (57.5%), aIPI 3: 21 (28.8%). Among 160 cycles of BRCAP chemotherapy, 5 (3.1%) on day 8, and 22 (13.7%) on day 15, were given without bortezomib due to a neutrophil count below 0.5 /L. The most common toxicities are shown in table 1 without significant differences between both arms. Twenty-one (32.8%) out of 64 patients had a positive PET2. Fifteen (26.8%) out of 56 patients who have finished the 4 cycles had a positive PET4 according to central review and were withdrawn of the trial. Table 1. Episodes of treatment-related adverse events Control arm: RCHOP n=166 Experimental arm: BRCAP n=160 Any grade Grade 3-4 Any grade Grade 3-4 Anemia 6 0 22 9 ( 5.6%) Neutropenia 31 26 (15.6%) 47 37 (23.1%) Thrombocytopenia 9 4 ( 2.4%) 16 5 ( 3.1%) Febrile neutropenia - 6 ( 3.6%) - 10 ( 6.2%) Fever 8 1 ( 0.6%) 8 0 Infection 4 1 ( 0.6%) 7 1 ( 0.6%) Nausea/vomiting 12 0 19 0 Peripheral neuropathy 7 1 ( 0.6%) 7 1 ( 0.6%) Diarrhea 4 0 8 0 Constipation 7 0 4 0 Hepatotoxicity 6 0 6 0 Conclusions: BRCAP regimen with bortezomib sc d1, 8, and 15 is feasible. Its main toxicity is hematological, and some patients cannot receive some doses of bortezomib due to neutropenia. Grade 3-4 non-hematological toxicity is rare, including peripheral neuropathy, and do not differ from RCHOP toxicity. 1.Ruan J et al, JCO 2011;29:690-7 Disclosures Sancho: CELLTRION, Inc.: Research Funding. Lopez-Guillermo:Roche, Celgene, Mundipharma, Gilead, Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background: Survival of DLBCL patients with high IPI treated with RCHOP immunochemotherapy is poor. In this population, the combination of RCHOP with new drugs is an attractive approach, along with performing an evaluation with PET/CT after 2 to 4 cycles to change the therapy if an early complete response is not achieved. Methods : We performed a clinical trial comparing 6 cycles of RCHOP vs 6 cycles of BRCAP, a modified RCHOP regimen changing vincristine by bortezomib 1.3 mg/m2 sc days 1, 8, and 15 of a 21-day cycle. Pre-phase therapy was permitted for patients who could not wait the results of the screening procedures to start therapy due to the aggressiveness of the disease. (ClinicalTrials.gov Identifier: NCT01848132). Patients younger than 71 yrs diagnosed with DLBCL and an age-adjusted IPI (aaIPI) 2-3 or aaIPI 1 with increased beta2microglobulin were eligible. The primary endpoint was the proportion of patients who survives free of event at 2 years. Centralized anatomopathology review was performed in all cases; samples were classified as germinal center B-cell-like (GCB) vs non-GCB subtypes by immunohistochemistry according to the Hans algorithm. PET/CTs were performed baseline, after 2, 4 and 6 cycles (PET2, PET4, and PET6), and were reviewed at real time by at least 3 experts of a central panel. Response at the end of therapy was analyzed following the visual method with the Deauville scale, and response after PET2 and PET4 was evaluated using the semiquantitative method. Persistent disease at PET4 was considered as failure of therapy and these patients were removed from trial treatment. EFS was calculated from diagnosis until event defined as death from any cause, relapse, progression or need of salvage therapy (defined as PET4 or PET6 positive). Overall survival (OS) was calculated from diagnosis until death for any cause. We present here a preliminary analysis of results. Results: One hundred and twenty-one patients were included; data on 113 are presented (diagnosis not confirmed in 6, data missing in 2). Median age was 57.1 yrs (range 23-70), 57 (50.4%) were males. Characteristics at diagnosis were: non-GCB subtype 32/87 (36.8%), immunohistochemical co-expression of myc/bcl2 56/82 (77.8%), stage III-IV 107 (94.7%), ≥2 extranodal locations 55/76 (72.5%), ECOG 2-3 36 (32.1%), increased LDH 88 (77.9%), increased beta 2 microglobulin 73 (64.6%), aaIPI 3: 32 (28.3%). No differences were found between treatment arms. Fifty-five patients were treated in the experimental arm (EA) and 58 in the control arm (CA). Twenty-eight (28.3%) out of 99 patients required of pre-phase treatment. The mean relative dose intensity for bortezomib was 88.3%. Data about the most frequent toxicity are shown in table 1. Twenty-nine (30.2%) out of 96 patients who have finished 4 cycles had a positive PET4 according to central review and were withdrawn to receive salvage therapy. Complete remission (CR) at the end of therapy (PET4-/PET6-) was observed in 44 (45.8%) patients. After a median follow-up of 9 months, estimated 12-mo EFS was 36.6%, and 12-mo OS was 82.9% in the whole series. Data of the subgroup analysis according the immunohistochemistry subtypes by Hans algorithm are show in table 2. Conclusions: In the present preliminary analysis, no significant differences were found between RCHOP and BRCAP in terms of CR and EFS in this very high-risk population of young DLBCL patients. However, in the subgroup analysis of patients with non-GCB disease, we found a significantly better CR rate in patients treated with BRCAP. A longer follow-up is needed to evaluate the real impact of this therapy on survival. Disclosures González-Barca: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria. Martín:Sevier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Sancho:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion, Inc: Research Funding; Sanofi: 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. López-Jiménez:Abbvie: Membership on an entity's Board of Directors or advisory committees; Velgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; MundiPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. López-Guillermo:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; MundiPharma: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Ramírez:Bristol-Myers-Squibb: Honoraria; Novartis: Honoraria; Roche: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees. Conde:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Amgen: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees.

Description: The major aim of this study was to update our preliminary report on the results of single-unit UCBT for adults with hematologic malignancies (Sanz GF et al, Blood2001; 98:2332). From May 1997 to June 2006, 92 patients underwent single-unit UCBT with a myeloablative conditioning that included thiotepa (TT), busulfan (BU; oral, 43; iv, 49 - iv single daily dose, 20), cyclophosphamide (72) or fludarabine (FLU; 20), and antithymocyte globulin (Lymphoglobulin, 32; Thymoglobulin [THY], 60). All received cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis and filgrastim to fasten engraftment. Diagnoses were acute lymphoblastic leukemia in 34, acute myeloblastic leukemia in 25, chronic myelogenous leukemia (CML) in 21, myelodysplastic syndrome in 5 and lymphoid malignanices in 7. The stage of the disease at transplant was advanced in 32 cases (35%). Median age and weight were 31 yr (range, 16–47) and 71 kg (range, 41–112). HLA match (HLA-A and -B at antigen and -DRB1 at allelic level) was 6/6 in 5 (5%), 5/6 in 33 (34%), and 4/6 in 54 cases (59%). The median number of nucleated cells (NCs) and CD34+ cells infused was 2.1 x 107/kg (range, 0.9–4.9) and 1 x 105/kg (range, 0.1–5.7) respectively. Median time to neutrophils 〉 0.5 × 109/L and platelets 〉 20 × 109/L was 22 days (range, 11–57) and 88 days (range, 27–188), and the cumulative incidence of myeloid and platelet engraftment was 90% at 60 days and 64% at 180 days, respectively. The cumulative incidence of grade II–IV acute GVHD was 36% (grade III–IV, 18%) and 28 of 55 patients at risk (51%) developed chronic GVHD (extensive in 19). The cumulative incidence of non-relapse mortality (NRM) at 30 days, 100 days, and 3 years was 8%, 25%, and 40% respectively. With a median follow-up of 26 months (range, 2–111), the cumulative incidence of relapse and the probability of disease-free survival (DFS) at 3 years were 21% and 39% (95% CI, 27–51%). Multivariate analyses showed that the absolute number of CD34+ cells in the UCB unit was the most important predictor of myeloid and platelet engraftment (P 〈 0.0001). The use of THY was related to faster platelet engraftment (P 〈 0.01) and lower incidence of acute GVHD (P 〈 0.0001). The development of grade II–IV acute GVHD was associated with slower platelet engraftment (P 〈 0.01) and greater NRM (P = 0.03). A higher age predicted for greater NRM (P = 0.005) whereas conditioning with TT, FLU, iv BU as a single daily dose, and THY (P = 0.004) and higher numbers of CD3+ cells infused (P = 0.0024) were associated with a lower NRM. Risk of relapse was lower for patients with CML (P = 0.02) and higher for those transplanted in advanced disease stage (P = 0.02). The only variable independently associated with DFS was the stage of the disease at transplant (P = 0.001). For patients transplanted in early stages DFS at 3 years was 52% (95% CI, 37–67%). The number of NCs and HLA mismatches did not impact any outcome. These results confirm that single-unit UCBT is a clear alternative for adults with high-risk hematologic malignancies, especially if transplanted in early stages. They also show that the universally accepted criteria for selecting the best UCB unit for transplantation in adults need to be modified.