ALBERT

Description: Glivec, a tyosine kinase inhibitor is the drug of choice for newly diagnosed chronic phase CML. Whilst Q-PCR is the most sensitive method to monitor response; cytogenetic analysis as well as FISH is routinely used in many laboratories. FISH has the advantage over marrow cytogenetic by allowing analysis of more cells, and cells in interphase, obviating necessity for an invasive marrow procedure. We performed 126 FISH studies using BCR-ABL dual color dual fusion translocation probe for 69 CML patients on imatinib. For each samples, 300 nucleated cells were counted. Clinical information was available from 57 patients (34 chronic-phase (CP), 7 accelerated phase (AP), 8 blastic phase (BT) and 8 post-BMT relapses). Most CP patients (94%) could achieve sustained complete hematological responses (CHR), including 14 of the 15 patients pre-treated with IFN. IFN pre-treated patients received imatinib generally late in the course of CP compared to those without (median 19M vs 0.8M, p

Description: Introduction and aim. Relapse following allogeneic hematopoietic stem cell transplantation (HSCT) is a major cause of treatment failure and is associated with a poor prognosis. Overall survivals are around 50% at 5 years following allogeneic HSCT in intermediate and high risk AML. Survivals remain less than 20% in poor-risk and very poor-risk patients based on the cytogenetic profile. Thus, prevention of relapse following allogeneic HSCT remains an unmet clinical need. Low-dose azacitidine maintenance post-HSCT has been shown to augment graft-versus-leukemia effect and may prolong survivals. We aim to prospectively evaluate the effect of azacitidine maintenance following allogeneic HSCT in high risk AML and MDS. Method. Consecutive patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in remission following first allogeneic HSCT or second allogeneic HSCT (from the original donor) were recruited. High risk AML in this study comprised patients with poor risk karyotype, secondary AML transformed from underlying MDS, presence of fms-like tyrosine kinase 3-internal tandem duplication (FLT3 -ITD) and non-remission before HSCT. Azacitidine was administered at 100mg daily for 3 days per cycle every 28 days until progression or a maximum of 8 cycles. The clinicopathologic and treatment characteristics were determined. The occurrence of graft-versus-host disease (GVHD) was determined. DNA chimerism was determined in the bone marrow before the initiation of azacitidine, after 4th and 8th cycles of azacitidine and at 1 year. DNA chimerism was determined by quantification of polymorphic short tandem repeat sequences. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier analysis. Results. Thirty-four patients with high-risk AML (N=31) and MDS (N=3) were recruited. The median duration of follow-up was 14 months (range: 2 - 44 months). Twenty-two patients received azacitidine maintenance after first allogeneic HSCT, whereas 12 patients received azacitidine maintenance after a second allogeneic HSCT from the same donor following relapse from a first allogeneic HSCT For patients receiving azacitidine after first HSCT, at a median follow-up of 18.5 months (range: 5- 36 months), the median PFS was not reached, and the median OS was 32 months (95% confidence interval [C.I.]: 24.85-39.15). The 24-month PFS and OS were 66.1% and 73.2% respectively. Acute and chronic GVHD occurred in 7 (31.8%) and 17 patients (77%). For patients receiving azacitidine after second HSCT, at a median follow-up of 14 months (range: 9 - 46 months), the median PFS and OS were 9 months (95% C.I.:6.94-11.04) and 14 months (range: 11.77 - 16.23 months). The 24-month PFS and OS were 25% and 14% respectively. Acute and chronic GVHD occurred in 1 (8.3%) and 5 (41.7%) patients respectively. In both groups, 100% donor chimerism was achieved during azacitidine maintenance. Conclusion. Azacitidine maintenance following first allogeneic HSCT resulted in favorable 2-year survivals in selected patients with high-risk AML and MDS. Nevertheless, survivals were poor despite azacitidine maintenance after second allogeneic HSCT from the same donor. Full donor chimerism was maintained during azacitidine maintenance. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: HSCT patients require platelet components (PC) for support of thrombocytopenia. Donors are tested for selected viruses to prevent transfusion-transmission infection (TTI), and PC are screened for bacteria and irradiated to prevent transfusion associated graft versus host disease (TA-GVHD). Leukocyte reduction (LR) is commonly, but not universally, used to mitigate the risks of acute transfusion reactions (ATR), allo-immunization, clinical refractoriness, and CMV TTI. However, donor testing, PC bacterial screening, and LR do not provide complete protection from ATR, transfusion related sepsis (TRS), refractoriness, CMV TTI, or residual risks of window period and emerging pathogen TTI. Amotosalen-UVA pathogen reduction treatment (A-PRT) inactivates a broad spectrum of pathogens (e.g. Zika), inhibits leukocyte antigen presentation and cytokine synthesis, and inhibits T-cell proliferation. A-PRT with LR has replaced bacterial screening, CMV serology, and gamma irradiation. Objective: To control cost, the Hong Kong Red Cross Blood Transfusion Service (HKRCBTS) has used whole blood platelet-rich-plasma (PRP) PC without LR. Based on data showing effective leukocyte inactivation by A-PRT, the HKRCBTS evaluated use of A-PRT buffy coat PC (BC PC) in platelet additive solution (PAS) without LR, bacterial screening, and gamma irradiation to manage costs, salvage more donor plasma, reduce TTI risk, and simplify production. Study Design and Methods : An open-label, prospective, sequential, two cohort study at Queen Mary Hospital, Hong Kong enrolled HSCT patients for up to 30 days of PC support with 100-day follow up. Cohorts were comparable for primary disease and type of HSCT. The first cohort received PRP PC prepared from CPD whole blood, a current HKRCBTS standard PC (Control-C). Five ABO-matched PRP PCs in 100% plasma were pooled without LR to yield ≥ 3 x 1011 platelets. C-PCs were screened for bacteria, gamma irradiated (2,500 cGy), stored up to 5 days at 22- 24 °C; and contained ~ 5 x 109 leukocytes. For the 2nd cohort, buffy coat PCs (BC PC) were prepared from CPD whole blood in PAS (SSP+, Macopharma, France). Five ABO-matched BC PC in 35% plasma-65% PAS were pooled, and prepared with A-UVA PRT to yield ≥ 3 x 1011 platelets (Test-T). T-PCs were not LR, not screened for bacteria, not gamma irradiated, stored for up to 5 days at 22- 24 °C; and contained ~ 5 x 108 leukocytes. HSCT patients ≥ 18 years expected to require PC were included. Exclusion criteria were: history of clinical refractoriness to platelet transfusion (2 successive 1-HR corrected count increments (CCI) 〈 5.0 x 103), immune thrombocytopenia, or disorders confounding 1-HR CCI determination. For both cohorts, a transfusion threshold of 10 x 109/L was specified for stable patients unless adjusted to 20 x 109/L for sepsis. Patients were not screened for HLA antibody at study entry. The efficacy outcome was the 1-hour (HR) count increment (CI), and the safety outcome was ATR incidence. Secondary (post-hoc) outcomes were the 1-HR CCI and the incidence of clinical refractoriness (two successive CCI 〈 5x103 per patient and transfusions with CCI 〈 5x103). Results: 64 patients were transfused (31 Control and 33 Test). Demographics were similar between cohorts (Table). The majority of patients had allogeneic HSCT from related donors. Mean pre-transfusion platelet counts were 〈 16 x 109/L. The mean PC dose and storage duration were similar between cohorts (Table). The 1-HR count increments (CI) and 1-HR CCI responses were within therapeutic ranges for both cohorts (Table). The proportion of transfusions with CCI responses 〈 5.0 x 103 and the proportion of patients with clinical refractoriness were less in the Test cohort (Table). ATRs trended lower with A-PRT (Test = 9.1%, Control = 19.4%, p=0.296).No patients had TRS or TA-GVHD reported during the active transfusion period. Day-100 engraftment (Table), HSCT-GVHD, mortality, and infectious disease complications were similar between cohorts. Conclusions: This exploratory study of A-PRT PC without LR demonstrated therapeutic 1-HR CCI responses, safety, and conserved HSCT engraftment. The proportions of transfusions with CCI 〈 5.0x103 and the proportion of patients with clinical refractoriness were less for A-PRT PC than conventional PC. A-PRT of pooled whole blood BC PC without LR offers the potential to improve PC supply, and to reduce the net cost of PRT PC by replacing other interventions. Table Table. Disclosures Corash: Cerus Corporation: Employment, Equity Ownership. Liu:Cerus Corporation: Employment, Equity Ownership. Huang:Cerus Corporation: Employment, Equity Ownership. Vermeij:Cerus Corporation: Employment, Equity Ownership. Stassinopoulos:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership.

Description: Introduction Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) comprising primary myelofibrosis (PMF) and myelofibrosis developing from either polycythemia vera (post-PV MF) or essential thrombocythemia (post-ET MF). Methods Two hundred and sixty-seven consecutive patients with MF (PMF, N=206); post-PV MF, N=26; post-ET MF, N=35) diagnosed between January 1988 and December 2013 at seven regional hospitals in Hong Kong were prospectively followed up. Data on the clinicopathologic features and treatment outcome were collected. Results The median duration of follow-up was 45 (1 – 247) months. The median overall survival (OS) was 65 months (95% confidence interval, CI: 56.3–73.7). The 5-year and 10-year OS were 52.2% and 26.7% respectively. On univariate analysis, factors associated with an inferior OS included age 〉 65 years (hazard ratio ,HR, =1.81; 95% CI:1.33–2.48; P

Description: Abstract 4367 Introduction The anti-myeloma effect of bortezomib, used as a single agent or in combination chemotherapy, is well recognized in various clinical studies. The aim of this study is to determine the feasibility of using the PAD combination (bortezomib, doxorubicin and dexamethasone) as upfront treatment in Chinese patients with newly diagnosed MM, followed by APBSCT. Method Patients between the ages of 18 to 65 year-old with newly diagnosed MM were recruited. PAD (bortezomib 1.3 mg/m2 on days 1, 4, 8 & 11; doxorubicin 9 mg/m2 on days 1 & 4; dexamethasone 40 mg on days 1-4, 8-11 & 15-18 during cycle 1 and days 1-4 during cycles 2-4) induction therapy was administered for four 28-days cycles, followed by autologous peripheral blood stem cell mobilization with cyclophosphamide 3 g/m2 plus G-CSF 5 mg/kg/BD. Subsequently, APBSCT was performed with high dose melphalan 200 mg/m2 conditioning. Results A total of 25 patients has been recruited so far (male:female = 14:11). The age ranged from 44 to 65 year-old (median 53). Eleven patients were of IgG subtype, 6 were IgD, 4 were IgA and 4 were kappa light chain disease. By Durie-Salmon staging, 22 were stage III, 2 were stage II and 1 was stage I. Seventeen (68%) patients have completed the four cycles of PAD induction therapy, while 3 (12%) are still having on-going PAD induction. Five (20%) patients withdrew from the PAD therapy. One patient developed disease progression after 2 cycles of PAD, while the other 4 developed serious adverse events with the first cycle of PAD, including 1 patient each with severe bradycardia, atrial fibrillation, severe sensory neuropathy and pulmonary haemorrhage. Of the 18 patients who had evaluable response to PAD (i.e. 17 patients who completed four cycles of PAD and 1 who progressed on PAD induction), the results were 3 CR, 7 VGPR, 5 PR and 3 NR. Fourteen of the patients with at least PR received APBSCT. Post-APBSCT responses were so far evaluable in 11 patients with 6 CR, 4 VGPR and 1 PR. Hence, PAD is a feasible and effective upfront induction therapy for Chinese patients with MM resulting in a satisfactory response rate. Nevertheless, significant adverse events may occur even early on with the treatment. Subsequent APBSCT further improved the response rate but long-term survival rate remains to be established. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4295 Syngeneic blood and marrow transplantation (BMT) has been applied in the treatment of many malignant or nonmalignant hematologic disorders with no or minimal and transient graft-versus-host disease (GVHD), much less transplant-related mortality (TRM) in contrast to allogeneic BMT, and lower relapse rate compared with autologous BMT. However, limited data in a single BMT center is not sufficient for statistical analysis. To evaluate the clinical outcomes of syngeneic BMT, CSBMT has performed a cooperative survey among BMT centers in mainland, Taiwan, and Hong Kong. From January 1964 to May 2009, 94 transplants from syngeneic donors have been performed in 32 BMT centers. The median age was 20 (1.5 to 51) years old. The diagnosis included AML (29 cases), SAA (26 cases), ALL (17 cases), CML (12 cases), lymphoma (3 cases), MDS (4 cases), neuroblastoma (2 cases), and large granular lymphocytosis (1 case). The main conditioning regimens were CYTBI or BUCY for malignant diseases, none or CY plus ATG for SAA. Bone marrow (BM, 34) or peripheral blood (PB, 49) or both BM and PB (11) as grafts were used. Five patients (SAA 2, AML 3) underwent the same donor's syngeneic BMT twice. One patient with large granular lymphocytosis and 1 case with SAA underwent the same donor's syngeneic BMT thrice. The median follow-up time was 28 months (1 month to 45 years). The median time for white blood cells 〉 1.0 × 109/L, and platelets 〉 20 × 109/L was 11 (2-30) days, 13 (0-122) days, respectively. Two patients (2.1%) had grade I acute GVHD (aGVHD), and 4 cases (4.3%) had grade II aGVHD. However, only one patient's specimen was consulted by pathologist. All aGVHD was controlled easily with low-dose steroid. No chronic GVHD was noted. Three-year disease-free survival (DFS) for the patients with nonmalignant disorders was 88.5%. Among them, the longest survivor was living and well for 45 years after transplant. Three-year DFS for the patients with malignant diseases was 62.9%. The overall survival rates at 3 years were 87.9%, and 69.5% for nonmalignant, and malignant diseases, respectively. 22 of 94 patients died after BMT (nonmalignant 3, malignant 19). The only cause of death for the patients with nonmalignant disorders was rejection. Relapse was the main cause of death in patients with malignancies (17/19). TRM was 2.1%. In conclusion, syngeneic BMT is a safe and effective therapeutic option for both nonmalignant and malignant hematologic disorders. Syngeneic donor, if available, should be the first choice in all cases of AA and hematological malignancies in general. The longest survivor of 45 years post-BMT is presented in this series. The good results and advantage of syngeneic BMT cast light on the potential utility of stored autologous placental-cord blood which is shared by the identical twin through the same placenta. Disclosures: No relevant conflicts of interest to declare.