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Pediatric regimens have improved outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL). However, results remain inferior to children with ALL. The Australasian Leukaemia and Lymphoma Group (ALLG) ALL06 study (anzctr.org.au/ACTRN12611000814976) was designed to assess whether a pediatric ALL regimen (Australian and New Zealand Children’s Haematology and Oncology Group [ANZCHOG] Study 8) could be administered to patients aged 15 to 39 years in a comparable time frame to children as assessed by the proportion of patients completing induction/consolidation and commencing the next phase of therapy (protocol M or high-risk [HR] treatment) by day 94. Minimal residual disease (MRD) response stratified patients to HR treatment and transplantation. From 2012 to 2018, a total of 86 patients were enrolled; 82 were eligible. Median age was 22 years (range, 16-38 years). Induction/consolidation was equally deliverable in ALL06 as in Study 8. In ALL06, 41.5% (95% confidence interval [CI], 30.7-52.9) commenced protocol M or HR therapy by day 94 vs 39.3% in Study 8 (P = .77). Median time to protocol M/HR treatment was 96 days (interquartile range, 87.5-103 days) in ALL06 vs 98 days in Study 8 (P = .80). Induction mortality was 3.6%. With a median follow-up of 44 months (1-96 months), estimated 3-year disease-free survival was 72.8% (95% CI, 62.8-82.7), and estimated 3-year overall survival was 74.9% (95% CI, 65.3-84.5). End induction/consolidation MRD negativity rate was 58.6%. Body mass index ≥30 kg/m2 and day 79 MRD positivity were associated with poorer disease-free survival and overall survival. Pediatric therapy was safe and as deliverable in AYA patients as in children with ALL. Intolerance of pediatric ALL induction/consolidation is not a major contributor to inferior outcomes in AYA ALL.

Pediatric regimens have improved outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL). However, results remain inferior to children with ALL. The Australasian Leukaemia and Lymphoma Group (ALLG) ALL06 study (anzctr.org.au/ACTRN12611000814976) was designed to assess whether a pediatric ALL regimen (Australian and New Zealand Children's Haematology and Oncology Group [ANZCHOG] Study 8) could be administered to patients aged 15 to 39 years in a comparable time frame to children as assessed by the proportion of patients completing induction/consolidation and commencing the next phase of therapy (protocol M or high-risk [HR] treatment) by day 94. Minimal residual disease (MRD) response stratified patients to HR treatment and transplantation. From 2012 to 2018, a total of 86 patients were enrolled; 82 were eligible. Median age was 22 years (range, 16-38 years). Induction/consolidation was equally deliverable in ALL06 as in Study 8. In ALL06, 41.5% (95% confidence interval [CI], 30.7-52.9) commenced protocol M or HR therapy by day 94 vs 39.3% in Study 8 (P= .77). Median time to protocol M/HR treatment was 96 days (interquartile range, 87.5-103 days) in ALL06 vs 98 days in Study 8 (P= .80). Induction mortality was 3.6%. With a median follow-up of 44 months (1-96 months), estimated 3-year disease-free survival was 72.8% (95% CI, 62.8-82.7), and estimated 3-year overall survival was 74.9% (95% CI, 65.3-84.5). End induction/consolidation MRD negativity rate was 58.6%. Body mass index ≥30 kg/m2and day 79 MRD positivity were associated with poorer disease-free survival and overall survival. Pediatric therapy was safe and as deliverable in AYA patients as in children with ALL. Intolerance of pediatric ALL induction/consolidation is not a major contributor to inferior outcomes in AYA ALL.

Background:

Extramedullary plasmacytoma (EMP) accounts for only 3 of plasma cell malignancies; others include multiple myeloma, plasma cell leukemia and solitary plasmacytoma of bone. The majority of EMPs are found in the upper respiratory tract. Other sites include the GI tract, bladder, CNS, thyroid, breast, testes, parotid gland, lymph nodes and skin. There are eight cases in the literature of adrenal plasmacytoma, however, only two were bilateral. We describe our recent experience of bilateral adrenal plasmacytoma and review of the literature. While EMP may present as aggressive locally destructive lesions, excellent local control can be achieved in a majority of cases. Follow-up should be lifelong due to risk of progression to multiple myeloma.

AbstractExtramedullary plasmacytoma (EMP) accounts for only 3% of plasma cell malignancies; others include multiple myeloma, plasma cell leukemia and solitary plasmacytoma of bone. The majority of EMPs are found in the upper respiratory tract. Other sites include the GI tract, bladder, CNS, thyroid, breast, testes, parotid gland, lymph nodes and skin. There are eight cases in the literature of adrenal plasmacytoma, however, only two were bilateral. We describe our recent experience of bilateral adrenal plasmacytoma and review of the literature. While EMP may present as aggressive locally destructive lesions, excellent local control can be achieved in a majority of cases. Follow-up should be lifelong due to risk of progression to multiple myeloma.

Late-onset combined immunodeficiency (LOCID), considered now a subset of common variable immunodeficiency (CVID) disorders, is characterized by a predominantly T-cell immune defect. LOCID has a distinct phenotype from CVID with a greater risk of lymphoproliferative complications. As compared to the CVID cohort, LOCID patients also have increased rates of splenomegaly and granulomatous disease. We report a case of central nervous system (CNS) T-cell lymphoma in a 67-year-old male as the presenting manifestation of LOCID. The patient achieved a complete response to therapy after 4 cycles of MATRix (methotrexate, cytarabine, and thiotepa) and 2 cycles of ICE (etoposide, carboplatin, and ifosfamide) chemotherapy followed by CNS-directed autologous stem cell transplantation. Intravenous immunoglobulin replacement was commenced to address the underlying immunodeficiency. Pulmonary lesions consistent with a diagnosis of granulomatous and lymphocytic interstitial lung disease (GLILD) were identified as a second noninfectious complication of LOCID. The pulmonary lesions resolved after chemotherapy and immunoglobulin replacement. The patient remains well with no evidence of disease recurrence now more than 18 months after completion of therapy. This is the first reported case of T-cell lymphoma in an adult patient with LOCID. Further study is needed to elucidate the mechanisms of transformation of B- or T-cells to lymphoproliferation in primary immunodeficiency patients as well as research to inform evidence-based therapeutic strategies for this challenging cohort of patients.

The terminal complement inhibitor eculizumab was recently shown to be effective and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we extended these observations with results from an open-label, non–placebo-controlled, 52-week, phase 3 clinical safety and efficacy study evaluating eculizumab in a broader PNH patient population. Eculizumab was administered by intravenous infusion at 600 mg every 7 ± 2 days for 4 weeks; 900 mg 7 ± 2 days later; followed by 900 mg every 14 ± 2 days for a total treatment period of 52 weeks. Ninety-seven patients at 33 international sites were enrolled. Patients treated with eculizumab responded with an 87% reduction in hemolysis, as measured by lactate dehydrogenase levels (P < .001). Baseline fatigue scores in the FACIT-Fatigue instrument improved by 12.2 ± 1.1 points (P < .001). Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin level occurred despite a reduction in transfusion requirements from a median of 8.0 units of packed red cells per patient before treatment to 0.0 units per patient during the study (P < .001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients (51%) achieved transfusion independence for the entire 52-week period. Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab were independent of baseline levels of hemolysis and degree of thrombocytopenia. Quality of life measures were also broadly improved with eculizumab treatment. This study demonstrates that the beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied. This trial is registered at http://clinicaltrials.gov as NCT00130000.

The terminal complement inhibitor eculizumab was recently shown to be effective and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we extended these observations with results from an open-label, non–placebo-controlled, 52-week, phase 3 clinical safety and efficacy study evaluating eculizumab in a broader PNH patient population. Eculizumab was administered by intravenous infusion at 600 mg every 7 ± 2 days for 4 weeks; 900 mg 7 ± 2 days later; followed by 900 mg every 14 ± 2 days for a total treatment period of 52 weeks. Ninety-seven patients at 33 international sites were enrolled. Patients treated with eculizumab responded with an 87% reduction in hemolysis, as measured by lactate dehydrogenase levels (P< .001). Baseline fatigue scores in the FACIT-Fatigue instrument improved by 12.2 ± 1.1 points (P< .001). Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin level occurred despite a reduction in transfusion requirements from a median of 8.0 units of packed red cells per patient before treatment to 0.0 units per patient during the study (P< .001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients (51%) achieved transfusion independence for the entire 52-week period. Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab were independent of baseline levels of hemolysis and degree of thrombocytopenia. Quality of life measures were also broadly improved with eculizumab treatment. This study demonstrates that the beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied. This trial is registered at http://clinicaltrials.govas NCT00130000.

Coyle: Amgen: Other: Travel support. Morley:Janssen: Honoraria, Other: Fees; AbbVie: Honoraria, Other: Fees; Roche: Other: travel support; Amgen: Honoraria, Other: Fees, travel support. Rambaldi:Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Omeros: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support from Gilead.; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Advisory board and speaker fees from Pfizer.; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Research grant from Amgen Inc.; BMS/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Astellas: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Received travel support., Research Funding; University of Milan: Current Employment. Furness:Amgen: Other: Travel Support. Desai:IQVIA: Current Employment. Mergen:Amgen: Current Employment, Current equity holder in publicly-traded company.Durable complete remissions can be achieved with a manageable safety profile using blinatumomab as second salvage in patients with aggressive R/R B-NHL following platinum based first salvage regimens

Introduction: In an open-label phase 2 study, blinatumomab demonstrated efficacy with a manageable safety profile as second salvage in patients with relapsed or refractory B-cell Non-Hodgkin’s lymphoma (R/R B-NHL) following platinum-based salvage regimens (Coyle et al. Leukemia & Lymphoma. 2020: 1-10). Blinatumomab is a BiTE® (bispecific T-cell engager) immuno-oncology therapy that activates endogenous cytotoxic T cells to kill target B cells. Here, findings from the updated analysis are reported (NCT02910063).

The aim of this study was to characterize individual-segment and overall patterns of VH gene usage in adult B-lineage acute lymphoblastic leukemia (ALL). Theoretical values of VH segment usage were calculated with the assumption that all VH segments capable of undergoing rearrangement have an equal probability of selection for recombination. Leukemic clones from 127 patients with adult B-lineage acute leukemias were studied by fingerprinting by means of primers for the framework 1 and joining segments. Clones from early preimmune B cells (245 alleles identified) show a predominance of VH6 family rearrangements and, consequently, do not conform to this hypothesis. However, profiles of VH gene family usage in mature B cells, as investigated in peripheral blood (6 samples), B-cell lymphomas (36 clones) and chronic lymphocytic leukemia (56 clones), are in agreement with this theoretical profile. Sequence analyses of 64 VH clones in adult ALL revealed that the rate of VH usage is proportional to the proximity of the VH gene to the JH locus and that the relationship can be mathematically defined. Except for VH6, no other VH gene is excessively used in adult ALL. VH pseudogenes are rarely used (n?=?2), which implies the existence of early mechanisms in the pathway to B-cell maturation to reduce wasteful VH-(DH)-JHrecombination. Finally, similar to early immunoglobulin-H rearrangement patterns in the mouse, B cells of ALL derive from a pool of cells more immature than the cells in chronic lymphoid B-cell malignancies.

The aim of this study was to characterize individual-segment and overall patterns of VHgene usage in adult B-lineage acute lymphoblastic leukemia (ALL). Theoretical values of VHsegment usage were calculated with the assumption that all VHsegments capable of undergoing rearrangement have an equal probability of selection for recombination. Leukemic clones from 127 patients with adult B-lineage acute leukemias were studied by fingerprinting by means of primers for the framework 1 and joining segments. Clones from early preimmune B cells (245 alleles identified) show a predominance of VH6 family rearrangements and, consequently, do not conform to this hypothesis. However, profiles of VHgene family usage in mature B cells, as investigated in peripheral blood (6 samples), B-cell lymphomas (36 clones) and chronic lymphocytic leukemia (56 clones), are in agreement with this theoretical profile. Sequence analyses of 64 VHclones in adult ALL revealed that the rate of VHusage is proportional to the proximity of the VHgene to the JHlocus and that the relationship can be mathematically defined. Except for VH6, no other VHgene is excessively used in adult ALL. VHpseudogenes are rarely used (n = 2), which implies the existence of early mechanisms in the pathway to B-cell maturation to reduce wasteful VH-(DH)-JHrecombination. Finally, similar to early immunoglobulin-H rearrangement patterns in the mouse, B cells of ALL derive from a pool of cells more immature than the cells in chronic lymphoid B-cell malignancies.

Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of cases of B‐lineage acute lymphoblastic leukaemia (ALL). We have examined bone marrow samples taken at presentation or relapse from 109 patients (79 adults and 30 children) and have performed sequence analysis of the complementarity determining region 3 (CDR3) on 65 alleles from 54 patients. We aimed to define immunoglobulin heavy chain (IgH) variable segment family use and investigate biological and structural features of the B cell in adult and childhood ALL. Using the FR1 fingerprinting method, a rearranged band was identified in 70 (89%) of 79 adult ALL and in 29 (97%) of 30 childhood ALL. This study found no preferential use or selection of IgH VH genes and no statistically significant structural differences between normal and leukaemic B cells in either adult and childhood ALL. An equal proportion of amplifiable cases of adult and childhood ALL uses more than one VH family gene (24/70, 34%, and 8/29, 27.5%, respectively). There were no significant differences in the structure or size of the CDR3 region and the variable (V) or joining (J) segment use in ALL patients compared to normal B cells. We observed that the N2 region was shorter than N1 in children whereas the opposite was observed in adults (not statistically significant). The J4 segment was a more common rearrangement in children than in adults, and in both groups J4 was more frequently associated with multiple D segment VDJ rearrangements. An increase in VH6 use in leukaemic alleles compared to normal B lymphocytes (2%) was observed but it was not statistically significant in our group of patients. Amongst children and adults, in‐frame CDR3 junctions occurred in 78% and 64% of rearranged alleles, respectively, compared to 75% of in‐frame sequences reported by others to occur among normal B cells.

68Ga prostate-specific membrane antigen (PSMA) PET/CT is a new imaging technique that is significantly more sensitive to prostate cancer lesions than other conventional imaging modalities. Various other benign and malignant neoplasms may also express PSMA and show uptake on PSMA PET/CT scan. We report a case of 66-year-old man who had a PSMA PET/CT scan for restaging of prostate carcinoma. A PSMA-avid left femoral lymph node was identified. Subsequent biopsy confirmed the diagnosis of follicular lymphoma. It is important to be aware of this possibility to avoid scan misinterpretation. Biopsy of any atypical or clinically unexpected lesions should be considered.

Coyle: Amgen Inc.: Other: non-financial relationship. Morley:Amgen Inc.: Honoraria, Other: non-financial; Roche: Honoraria, Other: non-financial, Research Funding. Rambaldi:Celgene: Consultancy; Roche: Consultancy; Omeros: Consultancy; Italfarmaco: Consultancy; Novartis: Consultancy; Amgen Inc.: Consultancy; Pfizer: Consultancy. Zhang:Amgen Inc.: Employment, Equity Ownership. Jung:Amgen Inc.: Employment, Equity Ownership. Franklin:Amgen Inc.: Employment, Equity Ownership.

Background: Autologous hematopoietic stem cell transplantation (autoHSCT) following response to salvage chemotherapy is the standard of care for patients with relapsed/refractory (r/r) aggressive B-cell lymphoma after first-line chemotherapy. Patients without complete metabolic response (CMR) to first salvage (S1) therapy have limited options and poor outcomes based on historical data. Blinatumomab, a bispecific T-cell engager (BiTE®) antibody construct that directs cytotoxic T cells to lyse B cells expressing CD19, has demonstrated a survival benefit in B-cell acute lymphoblastic leukemia and has antitumor activity in patients with r/r aggressive B-cell non-Hodgkin lymphoma (B-NHL), including patients previously treated with autoHSCT. This open-label, multicenter, phase 2 portion of an adaptive phase 2/3 study (ClinicalTrials.gov, NCT02910063) assessed the efficacy and safety of blinatumomab as a second salvage (S2) therapy for patients with aggressive r/r NHL who have not achieved CMR following platinum-based S1 chemotherapy.

Szer: Ra Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alnylam: Honoraria, Membership on an entity's Board of Directors or advisory committees. Marlton:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: 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, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: 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. Wei:Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Abbvie: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Cartwright:ROCHE: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roberts:Servier: Research Funding; Janssen: Research Funding; Genentech: Research Funding; AbbVie: Research Funding. Mills:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Meeting attendance sponsorship. Gill:Janssen: Membership on an entity's Board of Directors or advisory committees. Seymour:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Honoraria, 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, Other: Travel support, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background: Anthracylines are one of the major classes of drugs active against acute myeloid leukemia (AML). Increased doses of daunorubicin during induction therapy for AML have been shown to improve remission rates and survival. The ALLG used idarubicin in induction therapy at a dose of 9 mg/m2x 3 days (total dose 27 mg/m2) in combination with high-dose cytarabine and etoposide (Blood 2005, 105:481), but showed that a total idarubicin dose of 36 mg/m2was too toxic in this context (Leukemia 2001, 15:1331). In order to further improve outcomes in adult AML by anthracycline dose escalation, we conducted a phase 3 trial comparing standard to an increased idarubicin dose during consolidation therapy.

Imlay-Gillespie: Novartis: Honoraria. Arthur:BMS: Honoraria; Amgen: Honoraria; Amgen: Honoraria. Mackinlay:Roche: Research Funding; Sanofi Aventis: Research Funding. Mulligan:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Imlay-Gillespie: Novartis: Honoraria. Arthur:Amgen: Honoraria; Amgen: Honoraria; BMS: Honoraria. Mackinlay:Sanofi Aventis: Research Funding; Roche: Research Funding. Mulligan:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Mackinlay: Sanofi Aventis: Research Funding; Roche: Research Funding. Mulligan:Janssen: Consultancy, Honoraria, Speakers Bureau; Sanofi Aventis: Research Funding; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Imlay-Gillespie: Novartis: Honoraria. Arthur:Amgen: Honoraria; Novartis: Honoraria; BMS: Honoraria. Mackinlay:Roche: Research Funding; Sanofi Aventis: Research Funding. Mulligan:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi Aventis: Research Funding.

Background

Background

Background:

Background

Abstract 3612

A retrospective single-centre study was performed at Royal North Shore Hospital, NSW, Australia. The study includes patients who were diagnosed with AML between April 2009 and April 2012 and treated using the low-dose chemotherapy protocol. The group includes de novo AML patients as well as patients refractory to other therapies. The analysis included an oncology pharmacy audit as well as review of medical records and pathology results. Treatment consists of daily subcutaneous cytarabine 20mg/m2 and oral thioguanine 80mg for 14 to 21 day periods on monthly cycles with continued treatment for a period of 2 years. Peg-filgrastim is given concomittently with chemotherapy when patients become neutropenic. Response is assessed by bone marrow aspiration after treatment cycles. Routine supportive care is provided.Between March 2009 and May 2012, a total of 21 patients (13 with de novo AML and 9 with refractory/relapsed AML) received the low dose protocol. The median patient age was 75 (range 52 to 89 years). 12 (57%) patients had treatment-related or MDS-related AML. 7 (33%) patients had poor risk cytogenetics. A CR or CRi was achieved in 13 (62%) patients. The median follow-up time is 11.9 months. Of those that achieved CR or CRi, 9 patients (43%) have remained in remission with Kaplan-Meier estimated mean leukamia-free survival of 23.3 months (14–32.5, 95%CI). The Kaplan-Meier estimated mean overall survival for the group is 22.4 months (14.3–30.5, 95%CI). 6 patients have crossed over to other treatment modalities. 5 of 7 patients with poor cytogenetics achieved CR/CRi. 3 patients with abnormal cytogenetics achieved both morphologic and cytogenetic remission. The treatment was generally well tolerated. Outpatient administration of cytarabine is managed well with assistance from community nursing.The results reported here provide longer follow-up time and a larger number of patients as further evidence for the efficacy of the low-dose chemotherapy protocol and its feasibility in the outpatient setting. The remission rates acheived are comparable to those reported for intensive therapy with potential benefits of reduced toxicity, lower cost, fewer hospital admissions and improved quality of life. We suggest that this low-dose protocol may be a consideration for elderly patients deemed unsuitable or ineligible for intensive chemotherapy or azacitidine. A prospective study is underway to further evaluate this protocol.No relevant conflicts of interest to declare.

Arthur: AMGEN: Honoraria.

Abstract 2624

In paroxysmal nocturnal hemoglobinuria (PNH), lack of the GPI-anchored terminal complement inhibitor CD59 from blood cells renders erythrocytes susceptible to chronic hemolysis resulting in anemia, fatigue, thrombosis, poor quality of life (QoL), and a dependency on transfusions. Eculizumab, a terminal complement inhibitor, reduced intravascular hemolysis and transfusion requirements in transfusion dependent patients with normal or near-normal platelet counts in a randomized placebo-controlled trial (TRIUMPH). SHEPHERD, an open-label, non-placebo controlled 52-week phase III clinical study, is underway to evaluate the safety and efficacy of eculizumab in a broader PNH population including patients with significant thrombocytopenia and/or lower transfusion requirements. Eculizumab was dosed as follows: 600 mg IV every 7 days x 4; 900 mg 7 days later; and then 900 mg every 14±2 days. Eculizumab was administered to 97 patients at 33 international sites. In a pre-specified 6-month interim analysis, the most frequent adverse events were headache (50%), nasopharyngitis (23%), and nausea (16%); most were mild to moderate in severity. No infections or serious adverse events were reported as “probably” or “definitely” related to drug. Intravascular hemolysis, the central clinical manifestation in PNH and the primary surrogate efficacy endpoint of the trial, was significantly reduced in eculizumab patients as assessed by change in lactate dehydrogenase (LDH) area under the curve (p<0.001). LDH levels decreased from a median of 2,051 U/L at baseline to 270 U/L at 26 weeks (p<0.001; normal range 103–223 U/L). Control of intravascular hemolysis resulted in an improvement in anemia as transfusion requirements decreased from a median of 4.0 PRBC units/patient pre-treatment to 0.0 during treatment (p<0.001), approximately 50% of the patients were rendered transfusion independent (P<0.001), and hemoglobin levels increased (p<0.001). Fatigue, as measured by both the FACIT-Fatigue and EORTC QLQ-C30 instruments, was significantly improved with eculizumab treatment as compared to baseline (p<0.001 for each). Other EORTC-QLQ-C30 patient reported outcomes demonstrating improvement included global health status (p<0.001), all 5 patient functioning subscales (p<0.001) and 7 of 9 symptom/single item subscales (p=0.03). These results demonstrate that the beneficial effects of eculizumab in PNH are applicable to a much broader patient population than previously studied and further underscore that eculizumab treatment markedly reduces intravascular hemolysis, thereby providing clinical benefit to treated patients. The trial will complete in September 2006 and the final results from this 52-week study will be presented.

In paroxysmal nocturnal hemoglobinuria (PNH), lack of the GPI-anchored terminal complement inhibitor CD59 from blood cells renders erythrocytes susceptible to chronic hemolysis resulting in anemia, fatigue, thrombosis, poor quality of life (QoL), and a dependency on transfusions. Eculizumab, a terminal complement inhibitor, reduced intravascular hemolysis and transfusion requirements in transfusion dependent patients with normal or near-normal platelet counts in a randomized placebo-controlled trial (TRIUMPH). SHEPHERD, an open-label, non-placebo controlled 52-week phase III clinical study, is underway to evaluate the safety and efficacy of eculizumab in a broader PNH population including patients with significant thrombocytopenia and/or lower transfusion requirements. Eculizumab was dosed as follows: 600 mg IV every 7 days x 4; 900 mg 7 days later; and then 900 mg every 14±2 days. Eculizumab was administered to 97 patients at 33 international sites. In a pre-specified 6-month interim analysis, the most frequent adverse events were headache (50%), nasopharyngitis (23%), and nausea (16%); most were mild to moderate in severity. No infections or serious adverse events were reported as “probably” or “definitely” related to drug. Intravascular hemolysis, the central clinical manifestation in PNH and the primary surrogate efficacy endpoint of the trial, was significantly reduced in eculizumab patients as assessed by change in lactate dehydrogenase (LDH) area under the curve (p<0.001). LDH levels decreased from a median of 2,051 U/L at baseline to 270 U/L at 26 weeks (p<0.001; normal range 103–223 U/L). Control of intravascular hemolysis resulted in an improvement in anemia as transfusion requirements decreased from a median of 4.0 PRBC units/patient pre-treatment to 0.0 during treatment (p<0.001), approximately 50% of the patients were rendered transfusion independent (P<0.001), and hemoglobin levels increased (p<0.001). Fatigue, as measured by both the FACIT-Fatigue and EORTC QLQ-C30 instruments, was significantly improved with eculizumab treatment as compared to baseline (p<0.001 for each). Other EORTC-QLQ-C30 patient reported outcomes demonstrating improvement included global health status (p<0.001), all 5 patient functioning subscales (p<0.001) and 7 of 9 symptom/single item subscales (p≤0.03). These results demonstrate that the beneficial effects of eculizumab in PNH are applicable to a much broader patient population than previously studied and further underscore that eculizumab treatment markedly reduces intravascular hemolysis, thereby providing clinical benefit to treated patients. The trial will complete in September 2006 and the final results from this 52-week study will be presented.

Advanced age is a poor prognostic factor in acute myeloid leukaemia (AML). There is evidence that continuous low-dose chemotherapy with oral agents can achieve partial remission in AML and may be suitable as palliative therapy in elderly patients. Such low-dose treatment is usually complicated by drug-related neutropenia and thrombocytopenia. Granulocyte colony stimulating factor (G-CSF) may lessen the associated neutropenia and some anecdotal reports suggest G-CSF alone may be able to induce remission in AML. The study aim was to assess the benefits of combining an oral chemotherapeutic agent with continuous G-CSF. We describe a retrospective audit of 12 elderly patients with AML, diagnosed between 2000 and 2002, who were deemed to be either unfit for induction chemotherapy or who had failed to respond to intravenous chemotherapy. Patients were treated with continuous oral mercaptopurine, thioguanine, or hydroxyurea with concomitant G-CSF on three to seven days/week. The median age at diagnosis was 80 years (range 70–89 years). Eight (67%) had a preceding myelodysplastic syndrome. Eleven of the twelve patients died within the study period described, with a median survival of 9 months (95%CI 4.32–13.75). Eleven patients (92%) had a response to treatment, with blast disappearance obtained within 14 days of starting treatment. All patients achieved an increase in neutrophil count >0.5x109/L. Neutrophil recovery was attained within a mean of 13 days of treatment. From the onset of treatment, patients had neutrophils greater than 0.5 x109/L for 71% of the time, despite being on continuous cytotoxic treatment. Five patients (42%) had a platelet response with a rise in count above 100x109/L. A total of nine (75%) patients experienced a period of platelet transfusion independence and four (33%) patients became red cell transfusion independent for a mean of 4.6 and 4.8 months respectively. The analysis of this small cohort suggests that G-CSF administered in combination with one of the above oral chemotherapeutic agents, may be a novel way of providing treatment to elderly patients with AML which is both tolerable and of potential survival benefit.

Advanced age is a poor prognostic factor in acute myeloid leukaemia (AML). There is evidence that continuous low-dose chemotherapy with oral agents can achieve partial remission in AML and may be suitable as palliative therapy in elderly patients. Such low-dose treatment is usually complicated by drug-related neutropenia and thrombocytopenia. Granulocyte colony stimulating factor (G-CSF) may lessen the associated neutropenia and some anecdotal reports suggest G-CSF alone may be able to induce remission in AML. The study aim was to assess the benefits of combining an oral chemotherapeutic agent with continuous G-CSF. We describe a retrospective audit of 12 elderly patients with AML, diagnosed between 2000 and 2002, who were deemed to be either unfit for induction chemotherapy or who had failed to respond to intravenous chemotherapy. Patients were treated with continuous oral mercaptopurine, thioguanine, or hydroxyurea with concomitant G-CSF on three to seven days/week. The median age at diagnosis was 80 years (range 70–89 years). Eight (67%) had a preceding myelodysplastic syndrome. Eleven of the twelve patients died within the study period described, with a median survival of 9 months (95%CI 4.32–13.75). Eleven patients (92%) had a response to treatment, with blast disappearance obtained within 14 days of starting treatment. All patients achieved an increase in neutrophil count >0.5x109/L. Neutrophil recovery was attained within a mean of 13 days of treatment. From the onset of treatment, patients had neutrophils greater than 0.5 x109/L for 71% of the time, despite being on continuous cytotoxic treatment. Five patients (42%) had a platelet response with a rise in count above 100x109/L. A total of nine (75%) patients experienced a period of platelet transfusion independence and four (33%) patients became red cell transfusion independent for a mean of 4.6 and 4.8 months respectively. The analysis of this small cohort suggests that G-CSF administered in combination with one of the above oral chemotherapeutic agents, may be a novel way of providing treatment to elderly patients with AML which is both tolerable and of potential survival benefit.