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Objectives: This prospective multicentre study was conducted to assess the efficacy of the monoclonal anti-CD20 antibody rituximab in patients with chronic lymphocytic leukaemia (CLL). Secondary ob ...

Approximately 30 cases of adult acute lymphoblastic leukemia (ALL) emerge in Finland yearly. In literature 35 to 40% of those under the age of 60 are reported to recover from their illness. Of the 67 adult ALL patients treated at the Turku University Hospital from 1990 to 2010, 96% achieved remission. The five-year survival rate was 53%. After remission, an allogeneic stem cell transplant was performed for 22 patients (37%), with 38 patients (63%) continuing on cytotoxic drugs. There was no difference in survival between modes of treatment or risk groups.

The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on biochemical tumour markers beta 2-microglobulin (beta 2m), thymidine kinase (TK) and lactate dehydrogenase (LDH) were studied in eight patients with chronic lymphocytic leukaemia (CLL). The serum concentration of beta 2m rose by a median of 30% (range 8-50%) and serum TK by 101% (range 30-1414%). Serum LDH concentration, on the other hand, significantly decreased in all patients. The significant increases of beta 2m and TK could not be explained by progression of the disease or impaired renal function. Treatment with GM-CSF reduces the value of serum beta 2m and TK in assessment of tumour mass and disease activity.

The COP regimen has been widely used as a second-line treatment for advanced chronic lymphocytic leukemia (CLL). In this retrospective analysis of COP therapy 24 patients with CLL were included. All but two patients had previously been treated with alkylating agents and had become refractory to the therapy. The overall response rate to COP was 25%. Three patients had CR (12.5%), three PR (12.5%), five SD (21%), four PD (17%), and nine patients died (37.5%) during the COP treatments. The cause of death was neutropenic sepsis in all cases. The median duration of responses was 18 months. The median survival of all patients was 9.5 months. The survival of responders was 24.5 and of non-responders only 5.5 months. The COP regimen seems to have low efficacy in the treatment of refractory CLL and the toxicity of this regimen in the late disease phase appears to be unacceptable.

Introduction Multiple myeloma (MM) is characterized by a proliferation of plasma cells with a strong dependence on the bone marrow (BM) microenvironment. However, in some MM patients this proliferation escapes the BM resulting in extramedullary disease (EMD) with two types of involvement: 1) paraskeletal (PS) and 2) extramedullary (EM), involving either skin/lymph nodes (EMS) or organs (EMO). EMD is considered to be associated with poor prognosis. Autologous stem cell transplantation (ASCT) in MM is standard therapy in first line therapy in eligible patients, but only limited reports on outcome of EMD after ASCT exist. Methods Within the European Society for Blood and Marrow Transplantation (EBMT) registry, 4658 patients (female n=1898, male n=2760) who received upfront ASCT were reported between January 2005 and December 2014 with available data on EM involvement at time of diagnosis. 3802 patients had no EMD (MM group), while 677 had PS and 179 EM involvement, including EMS (n=68) or EMO (n=111). The median age of the patients was 59 years (range 22 - 77). The stage according ISS at diagnosis was I (n=1229), II (n=1174) and III (n=865). All patients received an upfront single (n=4250) or tandem (n=408) ASCT. Salmon and Durie classification stage B was seen more frequently in EM (31%), than in MM (17%) or PS (16%) (p< 0.001). More EM had ≥ 2 different sites of involvement than PS patients (20% versus 4%, p< 0.001). Tandem ASCT was applied to 15% in the PS group compared to 8% in the MM and 10% in the EM group (p< 0.001). Primary end point was 5 year progression-free survival (PFS). Results At ASCT 18% of MM patients achieved a complete remission (CR) compared to 20% of PS and 12% of EM patients (p=0.058). MM and PS patients showed similar 5 year PFS (28% versus 29%, p= 0.74) in the univariate analysis with a median PFS of 31 versus 33 months. In contrast, EM patients had a significant worse median PFS (21.5 months) and 5 year probability (22%) than MM patients (28%) as well as PS patients (29%) (p< 0.001). Five year probability of OS were higher in MM compared to PS (67% versus 63%, p=0.05) and to EM (67% versus 49%, p< 0.001). Furthermore, the difference in 5 year OS between PS and EM involvement reached statistical significance (63% versus 49%, p< 0.001). When analyzing PFS according to the number of sites involved, the median PFS in PS patients was 35 for 1 versus 24 months for ≥ 2 sites and in EM patients 24 versus 17 months (p=0.003). Other significant factors for worse PFS in the univariate analysis were: IgA-type (p< 0.001), Salmon and Durie stage B (p< 0.001), ISS II and III (p< 0.001, respectively), while favorable factors were CR (p< 0.001) and female sex (p< 0.001). In a subanalysis comparing EMS and EMO, the median PFS was significantly worse for EMS than EMO (20 versus 25 months, p=0.024). Cox proportional hazards regression considering independent factors for worse PFS yielded: EM (HR 2.88, 95% CI 1.90 - 4.37), IgA (HR 1.31, 95% CI 1.15 - 1.48) as well as Salmon and Durie stage B (HR 1.26, 95% CI 1.06 - 1.51), while improved PFS was seen for CR (HR 0.47, 95% CI 0.36 - 0.61) and ISS I (HR 0.70, 95% CI 0.60 - 0.83). Conclusion This EBMT registry study demonstrates that EMD manifestation in patients with MM is an independent risk factor for worse outcome after ASCT. Within the EMD group, non-paraskeletal extramedullary manifestation, EMS and involvement of 2 or more sites resulted in worse PFS. Disclosures Leleu: TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Delforge:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Kröger:Riemser: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding.

In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in more opportunistic infections. In a subgroup analysis of alemtuzumab trough levels during treatment by a sensitive enzyme-linked immunosorbent assay (ELISA) method, detectable levels were found in 4/6 complete and 0/3 partial responders. A relationship between alemtuzumab plasma levels, response and duration of lymphocytopenia was evident. We hypothesize that following combination therapy, the response may not be a function of the alemtuzumab levels, but the opposite, that plasma alemtuzumab levels are a function of the efficacy of the entire treatment, and the fewer leukemic target cells that are remaining, the higher are the levels of plasma alemtuzumab. This concept may well provide a guide for alemtuzumab dosage in future trials.

Allogeneic hematopoietic stem cell transplantation (ASCT) offers the only potentially curative therapy for myelofibrosis, a malignant myeloproliferative disease. The transplant-related mortality is still high, 10-48%, but use of reduced-intensity conditioning is less toxic and allows transplantation to be performed up to 65-70 years of age. Fabourable treatment response will be attained at least in a third of patients, in another third the disease will progress, and nearly one third will succumb due to transplant complications. Thirteen patients with myelofibrosis underwent ASCT at our institution between 1999 and 2009. The outcome of the patients treated with reduced-intensity conditioning corresponds well with those reported in the literature.

Indoleamine 2,3-dioxygenase (IDO) activity and expression is increased in many hematological malignancies, but has not been previously studied in chronic lymphocytic leukemia (CLL). We determined IDO activity and expression in 49 patients with CLL. We found that IDO activity is increased in CLL. This may have some influence on CLL progression.Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the catabolism of tryptophan, suppressing T-cell activity. IDO activity and expression are increased in many malignant diseases, including hematological malignancies. IDO expression can mediate immunotolerance to tumors. IDO activity and expression have not previously been studied in chronic lymphocytic leukemia (CLL).We measured IDO activity by calculating the kynurenine-tryptophan (kyn-trp) ratio. IDO and IDO2 gene expression was determined by using real-time polymerase chain reaction (PCR).In patients with CLL, the serum kyn-trp ratio--reflecting increased IDO activity--was significantly higher compared with controls, but in peripheral blood mononuclear cells (PBMCs)--mainly representing malignant B cells--the expression of genes encoding IDO and IDO2 enzymes was reduced.Increased IDO activity in patients with CLL may affect disease progression, although it originates from cells other than malignant B cells.

Achievement of complete response (CR) is a new goal of therapy for multiple myeloma (MM). By sensitive methods, the depth of response can be measured even among the patients in CR. We used a sensitive real-time quantitative polymerase chain reaction by allele-specific primers (qASO-PCR) to assess the level of minimal residual disease (MRD) in bone marrow of 37 patients with myeloma who had achieved CR/near-to-CR after autologous or allogeneic stem cell transplantation (SCT). Allele-specific primers could be successfully designed for 86% of patients. Three to six months after autotransplantation, the PCR target was not detectable in 53% of patients (16/30 patients), and the respective figure after allotransplantation was 71% (5/7 patients); the median sensitivity of PCR assay was0.002%. The proportion of patients without detectable PCR target was 22% of all autotransplanted patients. A threshold level of 0.01% in the qASO-PCR assay 3-6 months after SCT was found to be a useful cut-off limit to divide the patients into two prognostic groups: MRD low/negative vs. MRD high. Low/negative MRD after SCT was a significant predictive factor for the prolongation of progression free (70 vs. 19 months; P = 0.003) and suggestively also for overall survival. We conclude that not only CR but also its depth is important for the long-term outcome in MM.

Some reports suggest that blood stem cell mobilization is difficult in a proportion of patients with CLL. We evaluated this issue in a large cohort of CLL patients. One hundred and twenty-eight patients with CLL underwent blood stem cell mobilization during 1995-2005 in Finland. Ninety-five percent of the patients had received fludarabine. The most common mobilization regimen was intermediate-dose CY plus G-CSF (90 patients, 70%). At least 2 x 10(6)/kg CD34+ cells were collected after the first mobilization attempt in 83 patients (65%), whereas 45 patients (35%) failed to reach this collection target. No differences were observed between these patient groups with regard to age, time from the diagnosis to mobilization, number of previous treatment lines, number of fludarabine courses, time from the last fludarabine-containing chemotherapy to mobilization, disease status or degree of marrow infiltration. Patients who failed collection had platelets100 x 10(9)/l more commonly at the time of mobilization (30 vs 4%, P0.001). A significant proportion of patients with CLL were difficult to mobilize. Adequate marrow function including platelet counts100 x 10(9)/l seem to be important factors in terms of successful blood stem cell collection.

Chronic lymphocytic leukaemia (CLL) is a common adulthood mature B-cell neoplasm. Infections are the most important cause of mortality in this condition, and Streptococcus pneumoniae has been considered the most important single pathogen. We investigated the immunogenicity of 7-valent pneumococcal conjugate vaccine in patients with CLL. The study material comprised 52 patients with CLL and 25 age- and sex-matched controls. The subjects were vaccinated with Prevenar® pneumococcal conjugate vaccine. Serum samples were taken for antibody determinations before and four weeks after vaccination. Antibody response rates to vaccine antigens were lower in patients with CLL compared to controls. However, if the vaccine had been administered at an early stage of the disease, i.e. before commencement of chemotherapy and the development of hypogammaglobulinaemia, a significant vaccination response to at least six antigens was obtained in almost 40% of the CLL patients. Our results indicate that early administration of conjugate vaccine may be beneficial in CLL.

Objective: To investigate the long-term outcome of idarubicin- and cytarabine-based intensive chemotherapy in adult acute myeloid leukaemia (AML). Patients and methods: A total of 327 consecutive patients with de novo AML (promyelocytic leukaemia excluded) aged 16–65 yr were recruited into the study between September 1992 and December 2001. The latest follow-up data were collected in October 2006. After remission achievement with the first (conventional cytarabine) or second (high-dose cytarabine) chemotherapy cycle, three intensive consolidation courses each containing high- or intermediate-dose cytarabine were given. Results: A total of 268 patients (82%) achieved complete remission (CR). CR rate was 82% and 84% for patients

Although autologous stem cell transplantation (ASCT) has gained some popularity as a treatment option in patients with chronic lymphocytic leukaemia (CLL), limited multicentre data are available on the feasibility and efficacy of this approach. Between January 1995 and June 2005, 72 patients with CLL received ASCT in five Finnish centres. There were 45 men and 27 women with a median age of 57 years (38-69). The median time from diagnosis to ASCT was 32 months (6-181) and the median number of prior regimens 1 (1-4). All patients received blood stem cell grafts and CD34+ selection had been performed in 44 patients (61%). The most common high-dose regimen was a total body irradiation plus cyclophosphamide (38 patients, 53%). No early treatment-related deaths were observed. With a median follow-up of 28 months from ASCT, a relapse or progression has been observed in 27 patients (37%). The projected progression-free survival is 48 months (confidence interval (CI) 30-66). The projected median overall survival is 95 months (CI 74-101) from ASCT and is not influenced by graft selection or conditioning regimen used. Autologous stem cell transplantation is a feasible treatment option for CLL. Randomized trials against alternative treatments are needed to assess the impact of ASCT on the clinical course of CLL.

Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

Objectives: To evaluate early (

Limited experience is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in elderly patients with non-Hodgkin's lymphoma (NHL). In 1994-2004 altogether 88 NHL patients > 60 years old received ASCT in six Finnish transplant centres. There were 57 male and 31 female patients with a median age of 63 years (range 60-70 years); 17 patients were>65 years. The histology included diffuse large B cell (n = 29), mantle cell (n = 27), follicular (n = 15), peripheral T cell (n = 12) and other (n = 5). Disease status at ASCT was I complete remission/partial remission (CR/PR) in 53 patients, II CR/PR in 30 patients and other in five patients. The conditioning regimens included BEAC (n = 49), BEAM (n = 34), TBI-CY (n = 4) and other (n = 1). Eighty-four patients received PB grafts. The medians to reach neutrophils > 0.5 and platelets > 20 were 10 and 14 days, respectively. The early treatment-related mortality (TRM) (

One hundred patients with newly diagnosed multiple myeloma (MM) were treated with high-dose chemotherapy followed by single or double autologous stem cell transplantation (ASCT). Up-front treatment with a double ASCT tended to prolong progression-free and overall survival.

Patients with haemophilia A whose factor VIII (FVIII) concentration exceeds 5% have a mild disease and only bleed infrequently after trauma or surgical procedures. In these patients, desmopressin acetate (DDAVP) is a widely used haemostatic agent for bleeding prophylaxis before surgery because it is clinically effective and carries no risk of transmission of infectious diseases. We describe a patient with mild haemophilia A who had a massive anterior myocardial infarction (MI) after administration of DDAVP and who was successfully treated with a primary percutaneous coronary intervention (PCI) with stenting.

High-dose therapy followed by autologous stem cell transplantation (ASCT) has been considered a potential treatment approach in order to improve the poor prognosis in mantle cell lymphoma (MCL), but its role has not yet been clearly established. We analyzed retrospectively the outcome and prognostic factors in 48 consecutive patients with MCL scheduled for ASCT in five transplant centers. In 14 patients (29%), a sufficient amount of stem cells could not be collected. Mobilization failure was associated with female sex, blastoid cytology, and low hemoglobin level. Altogether 35 patients underwent ASCT, 24 patients as part of the first-line treatment and 11 patients later. After transplantation 28 patients (80%) remained in or achieved remission. Two patients died of transplant-related complications. During the median follow-up time of 38 months, nine patients have relapsed. The median event-free survival (EFS) was 39 months. Age over 60 years and elevated C-reactive protein level at diagnosis were associated with poorer outcome after transelantation. ASCT is an effective treatment in MCL with a high response rate and a longer survival than seen in conventionally treated patients. However, no plateau was seen in the EFS curve after ASCT. Whether cure Can be achieved in a proportion of patients with ASCT is currently unknown and should be studied in larger patient series with a longer follow-up.

The second-generation thrombopoietin receptor (TPO-R) agonists (romiplostim and eltrombopag) were introduced in the treatment of chronic immunologic thrombocytopenia (ITP) approximately 2 years ago...

Bisphosphonates do not delay engraftment after autologous SCT in patients with newly diagnosed myeloma

In this prospective study we evaluated the multiple effects of long-term GM-CSF therapy on blood counts, granulocyte functions and disease progression in patients with chronic lymphocytic leukemia (CLL) with chronic neutropenia and recurrent bacterial infections. The treatment duration varied from 2 to 12 weeks. The neutrophil count was raised in all patients, by the median of 6.6-fold. The neutrophil level of 1.0 x 10(9)/l was usually reached after two weeks. The initial dose of GM-CSF was 5 microg/kg/day, and 1-7 microg/kg/day was required to maintain the neutrophil level above 1.0 x 10(9)/l. Granulocyte functions, i.e. chemiluminescence (CL), random migration, and fMLP-stimulated chemotaxis were initially depressed in all patients when compared to healthy controls. GM-CSF enhanced significantly CL even when given at small doses (less than 1 microg/kg/day), even lower than the dose required to promote granulopoiesis. We conclude that GM-CSF is effective in improving CLL associated chronic neutropenia and also enhances impaired granulocyte chemiluminescence. Thus, GM-CSF could be helpful for giving chemotherapy without neutropenic delays and for prophylaxis of infectious complications in CLL patients.

The value of daily monitoring of the blood CD34+ cell concentration as a guide to the optimal timing of stem cell harvests was studied in 60 patients who underwent 66 stem cell mobilizations and 189 leukaphereses. There was a highly significant correlation between the blood CD34+ count and the CD34+ cell content in the apheresis product of the same day (r = 0.904, p < 0.01). Thus, the target yield of 4 x 10(6) CD34+ cells/kg can be harvested in one or two leukaphereses when the blood CD34+ cell count exceeds 50 x 10(6)/L. However, an insufficient harvest is to be expected when the blood CD34+ cell count is below 20 x 10(6)/L. The data from 35 autologous blood cell transplantations with a minimum CD34+ cell yield of 1.5 x 10(6)/kg showed that the recovery of blood neutrophil counts to 1.0 x 10(9)/L occurred in all patients within 9-14 days, but the time to recovery of the platelet counts to 20 x 10(9)/L may exceed 14 days, especially if the CD34+ cell content is below 4 x 10(6)/kg. Daily monitoring of blood CD34+ cell counts is a rapid and reliable means to guide the timing of stem cell collections. The count predicts well the CD34+ cell content of the harvests, the number of leukaphereses needed, and the speed of hematopoietic recovery.

Although iron overload is clinically significant, only limited data have been published on iron overload in haematological diseases. We investigated cardiac and liver iron accumulation by magnetic resonance imaging (MRI) in a cohort of 87 subjects who did not receive chelation, including 59 haematological patients. M-HIC (MRI-based hepatic iron concentration, normal values36 μmol/g) is a non-invasive, liver biopsy-calibrated method to analyse iron concentration. This method, calibrated to R2 (transverse relaxation rate), was used as a reference standard (M-HIC(R2)). Transfusions and ferritin were evaluated. Mean M-HIC(R2) and cardiac R(*) of all patients were 142 μmol/g (95% CI, 114-170) and 36.4 1/s (95% CI, 34.2-38.5), respectively. M-HIC(R2) was higher in haematological patients than in patients with chronic liver disease or normal controls (P0.001). Clearly elevated cardiac R2(*) was found in two myelodysplastic syndrome (MDS) patients with severe liver iron overload. A poor correlation was found between liver and cardiac iron (n=82, r=0.322, P=0.003), in contrast to a stronger correlation in MDS (n=7, r=0.905, P=0.005). In addition to transfusions, MDS seemed to be an independent factor in iron accumulation. In conclusion, the risk for cardiac iron overload in haematological diseases other than MDS is very low, despite the frequently found liver iron overload.

Abstract 290 Background: In CLL unmutated immunoglobulin heavy chain (IGH) genes, deletions of chromosome 17p or 11q and trisomy 12 are associated with an unfavorable outcome. At the outset of the present trial, phase II studies had shown promising results of immunochemotherapy with FC + rituximab, but the optimal immunochemotherapy regimen was not known, especially not for high-risk CLL patients. The aim of this trial was to improve the outcome of high-risk CLL by the addition of the monoclonal antibody alemtuzumab to the currently best known chemotherapy FC. Because of the recognized immunosuppressant activity of both treatment modalities, a low-dose alemtuzumab approach was chosen and vigilance and prophylaxis towards infection upheld throughout the study. Patients and methods: Previously untreated, fit patients up to 75 years of age with high-risk CLL in need of treatment according to the NCI/IWCLL guidelines were randomized to either oral FC (F 40 mg/m2 D1-3 and C 250 mg/m2 D1-3) or AFC: oral FC + subcutaneous (sc.) alemtuzumab 30 mg, in cycle 1 day -1 to +1, in cycles 2–6 30 mg day 1 only. Responses and endpoints were defined according to NCI/IWCLL guidelines. The primary endpoint was progression-free survival (PFS) on intent-to-treat with progression defined as no response after three cycles of induction treatment, progression of disease, relapse or death whichever occurred first. Secondary endpoints included the rate of complete remission (CR) and the rate of MRD – negative CR (by PCR or flow cytometry), overall survival (OS) and toxicity. We assumed that the addition of alemtuzumab to FC could increase the CR rate from the estimated 20% to 40% and the median PFS from 30 to 42 months. Results: The study population of 281 patients was included 2006–2010. As of July 2011 262 patients (93%) were evaluable, 129 in the AFC arm and 133 in the FC arm with a median follow-up of 30 months (range 2–63 months). The median age was 60 years (range 27–75) and 75% were males. Twelve % had Binet stage A, 54% stage B and 34% stage C. Beta-2-microglobulin was increased in the majority of the patients (median 3.7 g/ml). Eighty-nine % had unmutated IGH genes and FISH revealed 27% with del11q, 18% with trisomy 12 and 11% with del17p according to the hierarchical model. All risk parameters were well balanced between the two arms. Sixty-three% completed all six cycles in each arm, 73% completed at least 5 cýcles AFC while 66% completed 5 cycles FC. Efficacy: The overall response to AFC and FC was 88% and 80% respectively (NS), the CR rates were 57% and 45% respectively (P=0.049), and the rates of MRD-negative CR were 29% and 17% respectively (P Toxicity: Severe adverse events, mostly grade 3, were significantly more frequent following AFC than FC: 145 vs 90 (P Conclusion: In this selected high-risk CLL population, the addition of low-dose sc. alemtuzumab to FC induced a higher rate and higher quality of complete remission than FC alone, which, however, in this early analysis, did not yet translate into significantly prolonged PFS or OS. As expected, the combination is more immuno-suppressant than chemotherapy alone, leading to a higher number of opportunistic infections. With proper vigilance and prophylactic measures, these infections were manageable and did not lead to any excess mortality. Acknowledgments: The members of the Data Management and safety Board, Peter Hillmen, Stephan Stilgenbauer and Harald Anderson are thanked for their advice. The NovoNordisk Foundation, The Danish Cancer Society and Genzyme Corporation are thanked for research support. Disclosures: Geisler: Roche: Consultancy; Genzyme: Research Funding; Celgene: Consultancy; GSK: Consultancy. Walewski:4SC AG: Consultancy.

To review our policy of prophylactic treatment with intravenous immunoglobulin (i.v.IG) in chronic lymphocytic leukemia (CLL), we analyzed the infection history, serum IgG levels (S-IgG) and disease stage of 146 patients who were treated and followed at our institution in 1980-1989. S-IgG was available for 98 patients: 55% were hypogammaglobulinemic and 56% had had at least one severe infection. There were significant associations between S-IgG and the occurrence of infections (p less than 0.01) and disease stage (p less than 0.02). There was also a significant association between disease stage and occurrence of infections (p less than 0.001). Severe infections tended to accumulate in patients with subnormal S-IgG and advanced disease stage. Totally, 292 infections were recorded, and the incidence of moderate to severe infections was 0.47 per patient year. Infection mortality was high: 42 patients died of a severe infection (46% of all causes of death). Patients with a low S-IgG and advanced disease stage are the most susceptible to death from infection and would be most likely to benefit most from i.v.IG prophylaxis; however, the cost of this therapy is so high that strict individual consideration still remains crucial for treatment decisions.

Abstract 3360 Poster Board III-248 Purpose Richter's syndrome (RS) occurs in 2-8% of patients with chronic lymphocytic leukaemia (CLL). Clinical outcome has been generally poor after multiagent chemotherapy with median survival of less than 1 year. The aim of this retrospective study was to evaluate whether an autologous (AutoSCT) or an allogeneic stem cell transplantation (alloSCT) offers survival benefit. There are scant data addressing this issue. Patients and Methods As patients with RS are not identified separately in the current EBMT database a request was sent to all EBMT centres known to have performed SCT in patients with CLL, high-grade lymphoma or Hodgkin's lymphoma asking for RS transplants. Inclusion criteria included a diagnosis of RS prior to SCT, age > 18 years, and SCT performed 1997-2007. Centers who reported RS transplants received a questionnaire to collect detailed information on disease and transplant characteristics and outcome results. Data were analyzed by descriptive statistics and survival comparisons using log rank testing and Cox modelling. Fifty nine transplants for RS were reported by 25 centres, which is the largest cohort described. Thirty nine patients (25 (64%) male) underwent AutoSCT (of whom 8 underwent a subsequent alloSCT). The median age was 56 years (range, 30-68 years) and 44% (n=17) of transplants were performed after 2003, with a TBI-containing regimen used in 5 patients. A minority (36% of cases with data known) of patients had received ≥3 lines of prior therapy. The majority of transplants (n=32; 84%) were performed within a year of diagnosis of RS, and 91% of patients (with data known) were in CR/PR at time of transplant. With a median follow-up of 27 months, 15/39 (39%) patients were alive and 13 patients were disease-free, 21 (39%) had relapsed (19 died from relapse) and 5 (13%) died of treatment-related complications after ASCT. OS was 54% and 25% at 3 and 5 yrs respectively. Relapse incidence of 49%, NRM of 14% and PFS of 37% was observed at 3 yrs. Twenty patients (12 (60%) male) underwent alloSCT from a matched sibling donor (n=10), VUD (n=8) or an alternative donor (n=2) with PBSC used in 90% of cases. The median age was 57 years (range, 42-70 years) and 70% (n=14) of transplants were performed after 2003. A majority (80%) of patients underwent alloSCT within 1 year of diagnosis of RS and had received ≥3 lines of prior therapy (71% of known cases). Conditioning was reduced-intensity (RIC) in 14 cases and myeloablative in 6 patients, with TBI used for 4 patients and T-cell depletion strategies in 13. At time of alloSCT 14 patients were in CR/PR and 5 had progressive disease (missing data in 1 case). With a median follow-up of 15 months (range, 3-94 months) 11/20 (55%) patients were alive after alloSCT, of whom 7 were in CR/PR. Overall survival (OS) was 51% and 41% at three years and 5 years respectively. Conditioning (myeloablative vs RI-conditioning; P = 0.14) and source of donor (HLA-id sib vs VUD; P = 0.97) did not statistically influence outcome. OS was not statistically affected by the variables: prior lines of therapy < 3 or ≥3 lines (P = 0.72), CMV serostatus recipient/donor (P = 0.23), use of T-cell depletion (P = 0.88) or disease status at time of transplant. The 3 yr OS for patients transplanted in CR/PR was 51% compared to 27% for those transplanted with progressive disease (P = 0.18). Outcome was superior for patients < 60 yrs at alloSCT (p=0.04). Relapse incidence of 38%, NRM of 23% and PFS of 39% was observed at 3 yrs. Acute GVHD grade II to IV occurred in 30% of patients and there were no cases of extensive chronic GVHD within reported cases. Conclusion This is the largest study that has assessed the outcome after transplantation of patients with RS. In summary patients with RS who are chemosensitive to induction therapies may benefit from consolidation with transplantation strategies. Disclosures: No relevant conflicts of interest to declare.

Introduction Tyrosine kinase inhibitors (TKIs) such asimatiniband dasatinib have markedly improved treatment results in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Almost all patients achieve at least a complete hematological remission with induction therapy consisting of TKImonotherapyor TKI in combination with reduced-intensity chemotherapy and corticosteroids. In eligible patients, allogeneic hematopoietic stem cell transplantation (alloHSCT) has been recommended in first complete remission, but its role inpatientsachieving rapid and deep molecular remissions with TKI-driven therapy is unresolved. Methods We analyzed data fromPh+ ALL patients in the Finnish Hematological Registry (FHR), a population-based database maintained by the Finnish Hematology Association, which includes patients participating in clinical study protocols sponsored by theTheFinnish Leukemia Group, and patients treated outside of clinical trials. The FHR contains detailed information on baseline (demographics, laboratory values,cytogenetics, molecular assays) and follow-up (therapies given and outcome). Minimal residual disease (MRD) was evaluated by standardized RQ-PCR for the bone marrow BCR-ABL1 transcripts with a minimum sensitivity of 10e-5. Therapy responses were coded according to the EuropeanLeukemiaNetguidelines. Data from 128Ph+ALLpatients diagnosed between 1983-2016 were included in the analyses. Survival outcomes were calculated with the Kaplan-Meier method and compared with the log-rank test. Differences between groups were evaluated with the independent samples t-test for parametric numeric variables. Results Of the 128 patients included in the analyses, 78 patients (61%) had received TKI treatment and 50 patients were treated prior the TKI era. The TKIs used wereimatiniband dasatinib and majority of patients concurrently received combination chemotherapy for induction and consolidation. Of the patients not treated with TKIs, 19/50 (38%) received an allotransplant and the overall survival (OS) at 5 years was 58% in the allotransplanted vs. 3% in thenontransplantedpatients (P Discussion Our data indicate that up to 50% of patients withPh+ALLexperience long-term survival with TKI-driven therapy and noalloHSCT. However, robust predictive biomarkers are needed for selecting patients in whom the treatment-related mortality and morbidity ofalloHSCTare not warranted and could be treated with TKI-driven therapies only. MRD-negativity at 3 months may select for better outcome, but larger studies are needed for confirmation. In addition, disease-specific genomic andtranscriptomicprofiles (e.g. IKZF1, CDKN2 mutations) andimmunoreconstitutionmay prove valuable in this context. The advent of novel potent MRD-eradicating agents, such asbispecificCD3/CD19 antibodies, may further indicate re-evaluation of the role ofalloHSCTinPh+ALL. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Mustjoki: Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Ariad: Research Funding. Säily:Celgene: Other: Educational grant for congress participation; Amgen: Other: Educational grant for congress participation. Remes:Teva: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees. Porkka:Celgene: Research Funding.

Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide–based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-transplantation cyclophosphamide–based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD transplantation.

Plasman ferritiinipitoisuuden mittaus on elimistön rautapitoisuuden perusseulontakoe. Sen tulkinta ei ole kuitenkaan aina helppoa. Osoitettu raudanpuute voi olla rautahoidon aihe, vaikkei siihen liittyisikään anemiaa. Terveen henkilön varastorautavajaus korjataan yleensä suun kautta otettavilla valmisteilla.