Circulating subpopulations of non-cytotoxic ILCs in diffuse large B-cell lymphoma.

Non-cytotoxic innate lymphoid cells (ILCs) have been added to the list of immune cells that may contribute to the tumor microenvironment. Elevated levels of total ILCs and their subgroups have been reported in peripheral blood and tissue samples from patients with solid tumors, but their frequency in non-Hodgkin lymphomas, particularly diffuse large B-cell lymphoma (DLBCL), has not been clearly established. This study examined frequency and subset distribution in newly diagnosed DLBCL patients (nodal and extra-nodal) and compared it with blood specimens from healthy donors. The percentage of total ILCs (Lin - CD127+) was assessed by flow cytometry, as well as the four ILC subsets, defined as ILC1 (Lin - CD127 + cKit - CRTH2-), ILC2 (Lin - CD127 + cKit+/- CRTH2+), ILCp NCR- (Lin - CD127 + cKit + CRTH2- NKp46-) and NCR + ILC3 (Lin - CD127 + cKit + NKp46+). In the studied group of patients (n = 54), significantly lower levels of circulating total ILCs, ILC1, and ILCp NCR- were observed compared to the control group (n = 43). Similarly, there was a statistically significant decrease in the median frequency of NKp46 + ILC3 cells in lymphoma patients. Analysis of the ILC2 subpopulation showed no significant differences. The correlation of the distribution of individual subpopulations of ILCs with the stage and location of the tumor was also demonstrated. Our results suggest that circulating ILCs are activated and differentiated and/or differentially recruited to the lymph nodes or tumor microenvironment where they may be involved in antitumor defense. However, our observations require confirmation in functional studies.

Onychoscopy of non-infectious nail abnormalities in patients after allogeneic haematopoietic stem cell transplantation.

Nail abnormalities after allogeneic haematopoietic stem cell transplantation procedure (alloHSCT) are often reported. Usually, they are related to chronic graft-versus-host disease (cGvHD). So far, only clinical manifestations of selected nail abnormalities have been described, without the presentation of dermoscopic images. In this article, we present morphologic and dermoscopic manifestations of potential non-infectious nail abnormalities in patients after alloHSCT procedure based on reviewed literature and our own experience with dermoscopic iconography. In majority of studies published till now, nail changes are not connected to severity of other cGvHD symptoms; however, e.g. the presence of pterygium inversum unguis may be an indicator of lung dysfunction. As nail changes may be an early sign of cGvHD and always present in association with other manifestations, routine clinical assessment should include nails examination. Knowledge of possible presentation of nail involvement after alloHSCT may be valuable for treating physician.

What is the outcome in patients with acute leukaemia who survive severe acute graft-versus-host disease?

BACKGROUND: Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic haematopoietic stem cell transplantation (HSCT). With new promising therapies, survival may improve for severe aGVHD. OBJECTIVES: We wanted to analyze the long-term outcome in patients who survive severe aGVHD. METHODS: This study was a landmark analysis of 23 567 patients with acute Leukaemia who survived for more than 6 months after HSCT, 2002-2014. Patients alive after severe aGVHD (n = 1738) were compared to controls. RESULTS: Patients with severe aGVHD had higher non-relapse mortality (NRM) and higher rate of extensive chronic GVHD (cGVHD) than the controls (P < 10-5 ). The probability of relapse was significantly lower in the severe aGVHD group, but Leukaemia-free survival (LFS) and overall survival were significantly lower than for the controls (P < 10-5 ). Five-year LFS in patients with severe aGVHD was 49%, as opposed to 61% in controls with no or mild GVHD and 59% in patients with moderate GVHD. CONCLUSIONS: HSCT patients who survive severe aGVHD have higher risk of developing extensive cGVHD, a higher NRM, a lower relapse probability, and lower LFS than other HSCT patients. This study is a platform for outcome analysis in patients treated with novel therapies for acute GVHD.

Comparison of the cryoprotective solutions based on human albumin vs. autologous plasma: its effect on cell recovery, clonogenic potential of peripheral blood hematopoietic progenitor cells and engraftment after autologous transplantation.

BACKGROUND AND OBJECTIVES: Cryopreservation of peripheral blood hematopoietic progenitor/stem cells (PBPCs) requires the addition of cryoprotectant such as DMSO, often prediluted using human serum albumin solution (HSAS). The goal of our study was to verify whether the HSAS may be replaced by autologous plasma (AP) without negative impact on PBPCs quality and engraftment. AP usage is less expensive and allows performing cell preparation in a 'closed system', and hence to reduce the risk of product contamination. MATERIALS AND METHODS: Peripheral blood progenitor cells from 18 patients were divided into two aliquots (500 µl) placed in separate vials, each containing 7·5% DMSO prediluted with 5% HSAS or AP. Post-thaw cell recovery and clonogenic potential was evaluated. During clinical part of the study, the impact of both cryoprotective solution on hematopoietic engraftment was evaluated in two cohorts (n = 26) matched for diagnosis, age and the number of transplanted CD34+ cells. RESULTS: The median recovery of nucleated cells and the number of colony-forming units did not differ between tested cryoprotective mixtures. For AP mixture, neither total protein nor albumin concentration of plasma correlated with cell recovery and clonogenic potential of the PBPCs after cryopreservation. In clinical evaluation, the median time to leucocyte recovery and reconstitution of neutrophils was comparable in both groups: 10 days. We did not observe either significant difference with regard to the time of platelet recovery (median: 15 days for AP vs. 16 for HSAS; P = 0·79). CONCLUSIONS: HSA in cryoprotective mixture may be replaced by AP without negative impact on cell recovery, clonogenic potential or engraftment.

Allogeneic hematopoietic cell transplantation is equally effective in secondary acute lymphoblastic leukemia (ALL) compared to de-novo ALL-a report from the EBMT registry.

Secondary acute lymphoblastic leukemia (s-ALL) comprises up to 10% of ALL patients. However, data regarding s-ALL outcomes is limited. To answer what is the role of allogeneic hematopoietic cell transplantation (HCT) in s-ALL, a matched-pair analysis in a 1:2 ratio was conducted to compare outcomes between s-ALL and de novo ALL (dn-ALL) patients reported between 2000-2021 to the European Society for Blood and Marrow Transplantation registry. Among 9720 ALL patients, 351 (3.6%) were s-ALL, of which 80 were in first complete remission (CR1) with a known precedent primary diagnosis 58.8% solid tumor (ST), 41.2% hematological diseases (HD). The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between ST and HD patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL. To conclude, patients with s-ALL who received HCT in CR1 have comparable outcomes to patients with dn-ALL.

Impact of different dimethyl sulphoxide concentrations on cell recovery, viability and clonogenic potential of cryopreserved peripheral blood hematopoietic stem and progenitor cells.

BACKGROUND AND OBJECTIVES: The procedure of autologous hematopoietic stem/progenitor cell transplantation requires cryopreservation. Addition of DMSO is necessary to secure the viability of such cells, but this solvent is potentially toxic to stem cells' recipient. 10% DMSO solution is used by the majority of transplant centres. The aim of our study was to test if DMSO concentration might be reduced without negative impact on cell recovery and clonogenicity. MATERIALS AND METHODS: Samples were prospectively collected from 20 patients. Small volumes of leukapheresis products were frozen with different cryoprotective mixtures, containing 10%, 7·5%, 5% and 2·5% DMSO, respectively. The quality of cryoprotective mixtures was evaluated based on recovery, viability and clonogenic potential of hematopoietic stem cells after defreezing. RESULTS: Reduction in DMSO concentration to 7·5% or lower was associated with decreased recovery of nucleated cells. In contrast, the number of colonies was highest for 7·5% DMSO with significant differences when compared to 10% DMSO solution. CONCLUSION: Reduction in DMSO concentration from 10% to 7·5% may have favourable impact on hematopoietic recovery after autologous transplantation. The findings require confirmation in a clinical setting.

Retrospective evaluation of health event data recording on 50 dairies using Dairy Comp 305.

The purpose of this study was to characterize health data recording in herds using Dairy Comp 305 (Valley Agricultural Software, Tulare, CA), focused on the most common diseases of dairy cattle: mastitis, uterine infection (metritis), and diseases causing lameness. Herds using Dairy Comp 305 were chosen for the study because it was the most commonly used program in the United States (35% of operations using computer records/60% of cows on operations using computer records), the authors were familiar with the program, and there was convenient access to herds using the program. Specific objectives were to (1) determine the percentage of herds recording mastitis, metritis, and diseases causing lameness and the number of user-defined events used to record those diseases, (2) identify the information recorded in the remarks about the event used for each disease, and (3) evaluate the consistency of health event remarks recorded. A convenience sample of 50 Dairy Comp 305 compressed cow files was obtained directly from dairies that the authors had contact with or files obtained from industry consultants. The 50 herds included in the study were from 9 different states: California (n=3), Colorado (n=2), Iowa (n=2), Idaho (n=8), Minnesota (n=2), New Mexico (n=9), Oregon (n=2), Texas (n=2), Utah (n=1), and Washington (n=19). The average number of milking cows of the herds was 3,053 (median=2,217), ranging from 310 to 12,490 cows. The majority of dairies in this study were recording health events associated with mastitis, metritis, and diseases causing lameness. However, as reported previously, most health records observed in the current study lacked the accuracy and consistency needed to be useful for evaluating and informing herd-level health management decisions. This situation likely reflects the intended use of those records by farm personnel and the user-defined nature of health records in the absence of accepted industry standards or recommendations for health data-recording practices.

KIR/HLA gene combinations influence susceptibility to B-cell chronic lymphocytic leukemia and the clinical course of disease.

The aim of this study was to analyze the association between gene polymorphisms of killer-cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands and susceptibility to B-cell chronic lymphocytic leukemia (B-CLL) and the clinical course of disease. The distribution of individual KIR genes in 197 B-CLL patients and 200 controls was similar, except for a tendency for lower frequencies of the KIR2DS3 and KIR2DL5 genes among B-CLL patients (26.9% vs 35.5%, P = 0.06, 46.2% vs 55.5%, P = 0.06). The associations between KIR2DS3 and B-CLL reached statistical significance in women (P = 0.05). Moreover, we found a trend toward a lower frequency of genotypes with the presence of five or six activating KIR genes in B-CLL patients compared to controls (20.8% vs 29.0%, P = 0.06), and a significantly higher frequency of individuals possessing genotypes with a prevalence of inhibitory over activating KIR genes (ratio < 0.71) among B-CLL patients (P = 0.04). The HLA-Bw4 specificity was significantly reduced among B-CLL patients (48.7% vs 63.0%, P = 0.005), which resulted from a decreased frequency of HLA-Bw4(Thr80) (21.6% vs 32.0%, P = 0.02). Moreover, among HLA-Bw4-positive individuals, progression-free survival (PFS) tended to be higher in the presence of KIR3DS1 (77% ± 9% vs 39% ± 13%, P = 0.07). However, in B-CLL patients, the presence of HLA-C2 was associated with decreased PFS (49% ± 9% vs 75% ± 7%, P = 0.02), and among HLA-C2-positive patients, the probability of PFS was significantly reduced in the absence of KIR2DS1 (34% ± 11% vs 77% ± 7%, P = 0.007). Our results indicate that the pattern of inhibitory/activating KIR genes, together with their HLA ligands, is associated with susceptibility to B-CLL and affects the clinical course of this disease.

Forecasting financial asset processes: stochastic dynamics via learning neural networks.

Models for financial asset dynamics usually take into account their inherent unpredictable nature by including a suitable stochastic component into their process. Unknown (forward) values of financial assets (at a given time in the future) are usually estimated as expectations of the stochastic asset under a suitable risk-neutral measure. This estimation requires the stochastic model to be calibrated to some history of sufficient length in the past. Apart from inherent limitations, due to the stochastic nature of the process, the predictive power is also limited by the simplifying assumptions of the common calibration methods, such as maximum likelihood estimation and regression methods, performed often without weights on the historic time series, or with static weights only. Here we propose a novel method of "intelligent" calibration, using learning neural networks in order to dynamically adapt the parameters of the stochastic model. Hence we have a stochastic process with time dependent parameters, the dynamics of the parameters being themselves learned continuously by a neural network. The back propagation in training the previous weights is limited to a certain memory length (in the examples we consider 10 previous business days), which is similar to the maximal time lag of autoregressive processes. We demonstrate the learning efficiency of the new algorithm by tracking the next-day forecasts for the EURTRY and EUR-HUF exchange rates each.

[Shape analysis of retroperitoneal tumors in childhood in magnetic resonance imaging]. / Formanalyse in der Magnetresonanztomografie - Landmarken und Objektdifferenzierung bei retroperitonealen Tumoren im Kindesalter.

2D-shape analysis of biological objects is described first in 2007 with MRI-data (magnetic resonance imaging) of renal tumours of infancy. For shape analysis the evaluation of landmarks is necessary (n >2). In this study 24 landmarks are selected. Every object is described by these landmarks. The shape is the standardised and centred object. The procedure is applied on transversal as well as on frontal images. The results for frontal and transversal images are compared. Tumours of different origin, topography and size can be analysed. The differentiation of relevant landmarks is important for statistical and medical reason. In this study, evaluation of landmarks and their possibility for tumour differentiation is demonstrated.

H2S, VOC, TOC, electronic noses and odour concentration: use and comparison of different parameters for emission measurement on air treatment systems.

Odour measurement via olfactometry is expensive and has a low accuracy compared with chemical or physical methods. In addition, olfactometry is not suited for online monitoring. Hence, an accurate online method for emission measurement would be an enormous improvement. There are several options to more or less replace the offline olfactometry by online measurement available today. Most common are H2S-concentration as a single gas parameter and VOC and TOC as composite parameters. A fairly new development are multi sensor arrays, usually referred to as "electronic noses" which carry out non-specific gas measurement and deliver measurement data that can visualized as a fingerprint diagram. This paper outlines the use of these different parameters and compares the results to those gained via olfactometry of several case studies.

[Statistical analysis of renal tumours with infants]. / Statistische Analyse der Form von Nierentumoren bei Kleinkindern.

By using medical imaging a diagnosis for a patient is to be given. The shape of three-dimensional medical relevant objects in the human body is the basis for an accurate diagnosis. Based on the correct diagnosis, the appropriate therapy can be decided. In the following study the shape of renal tumours is explored by the mathematical method of shape analysis and by the test of Ziezold (1994). There are n=24 patients whose frontal view records are available. The possibility of classification can be presented only in an exploratory manner, due to the low case numbers of patients.

Beta-2-microglobulin level predicts outcome following autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

Despite the widespread use of high-dose therapy combined with autologous hematopoietic stem cell transplantation (autoHSCT), the outcomes of multiple myeloma (MM) treatment remain variable. The aim of this study was to define pretransplantation factors that influence outcomes following autoHSCT in patients with MM. Eighty-one MM patients, aged 51 years (range 31-70 years), undergoing first autoHSCT were included in the analysis. Thirty patients were in complete remission and 51 were in partial remission. The conditioning regimen was based mainly on melphalan (200 mg/m(2) intravenous [iv]). The following factors were tested for their prognostic significance: beta-2-microglobulin (B2M), lactate dehydrogenase, monoclonal protein level, bone marrow plasma cell percentage (PL), hemoglobin level, age, interval from diagnosis to autoHSCT, and number of transplanted CD34-positive cells. The transplant-related mortality at day 100 was 3.7% (3/81). The incidence of progression at 9.2 years was 71% for patients with elevated B2M, and 32% for those where B2M was within normal limits (P = .02.) The probability of PFS was decreased for patients with B2M > or = versus < normal limits (29% vs 68%; P = .02) and PL > or = versus < 5% (0% vs 45%; P = 0.03). In a multivariate analysis B2M remained the only factor associated with increased risk of progression (relative risk [RR] = 3.3; P = .03) and reduced probability of PFS (RR = 3.3; P = .03). We concluded that B2M level measured at first autoHSCT was a useful predictor for progression and PFS in MM patients.

Prediction of nonrelapse mortality for patients surviving 100 days after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Patients who survive 100 days after allogeneic hematopoietic stem cell transplantation (alloHSCT) are at risk for chronic graft-versus-host disease and other potentially fatal complications. As the symptoms overlap and the differential diagnosis is difficult, the goal of this study was to verify whether basic laboratory evaluation performed on day +100 may allow identification of patients who are at high risk for nonrelapse mortality (NRM), independent of the underlying complications. PATIENTS AND METHODS: We analyzed 255 patients, mean age 29 years (range, 10-56 years), who remained alive and disease-free on day +100 after myeloablative alloHSCT from an HLA-identical sibling (n=177) or a matched unrelated volunteer (n=78), performed in a single institution between 1992 and 2003. RESULTS: Upon univariate analysis, the following laboratory parameters were associated with increased incidence of NRM: peripheral blood neutrophils<1.5x10(9)/L, platelets<100x10(9)/L, hemoglobin<11 g/dL, total protein<60 g/L, elevated plasma aspartate aminotransferase, elevated alkaline phosphatase, and elevated bilirubin. Upon multivariate analysis, only decreased protein (hazard ratio [HR]=6.97 [3.3-14.7], P<.0001) and elevated bilirubin (HR=3.52 [1.91-6.48], P<.0001) independently influenced the risk for NRM. The cumulative incidence of NRM equaled 6% if none of the above factors was present; 10% for hyperbilirubinemia alone; 22% for hypoproteinemia alone; and 70% for hyperbilirubinemia and hypoproteinemia, both present. CONCLUSIONS: A simple laboratory evaluation is highly predictive of the risk for NRM in patients surviving 100 days after alloHSCT. The prognosis is particularly poor for patients with hypoproteinemia and hyperbilirubinemia. These abnormalities may reflect impaired liver and intestine functions due to various posttransplantation complications.

Impact of activating killer immunoglobulin-like receptor genotype on outcome of unrelated donor-hematopoietic cell transplantation.

BACKGROUND: In a previous study we demonstrated that incompatibility regarding ligands for inhibitory killer immunoglobulin-like receptors (KIRs) is associated with a survival advantage following unrelated donor-hematopoietic cell transplantation (URD-HCT). The goal of the present analysis was to evaluate whether genotype of activating KIRs of the donor may have an impact on the outcome of URD-HCT. PATIENTS AND METHODS: Twenty-five URD-HCT recipients with hematological malignancies, mean age 27 years (range, 14-43 years), were included in the analysis. The conditioning regimen was myeloablative and based on chemotherapy alone (n = 20) or total body irradiation (n = 5). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine, methotrexate, and pretransplant antithymocyte globulin. Patients were grouped according to their donors' activating KIR genotype including two loci: KIR2DS1 and KIR2DS2. RESULTS: The presence of KIR2DS1 in the donor (n = 16/25) was not demonstrated to influence outcome. In contrast, the presence of KIR2DS2 (n = 13/25 donors) was associated with decreased probability of overall survival (0% vs 92%, P = .04) and disease-free survival (0% vs 92%, P = .046). The reason for failures in the KIR2DS2-positive group was chronic GVHD (n = 4), acute GVHD (n = 2), and relapse (n = 1). The cumulative incidence of nonrelapse mortality equaled 90% for the KIR2DS2-positive group and 8% for the KIR2DS2-negative group (P = .09). CONCLUSION: The presence of KIR2DS2 gene in the donor is associated with a high risk of mortality following URD-HCT, resulting mainly from the incidence of severe GVHD. Whether this effect is associated with the activity of natural killer cells or KIR-bearing T lymphocytes requires further investigation.

[Explanation and forecast: relapse of juvenile offenders]. / Erklirung und Vorhersage von "Rückfälligkeit" bei jugendlichen Straftätern.

On the basis of n=82 juvenile offenders from a prison for juvenile offenders in Rheinland Pfalz the model of the logistic regression is compared with a procedure from the family of the neural nets in its efficiency to explain and predict "relapse" in form of a renewed imprisonment or prosecution /police search after dismissal. The group which can be examined is limited by the population of the prison for juvenile offenders and the explaining variables for "relapse" as "addicted to drugs" present non-metric scaling. For the explanation only probabilities for "relapse" can be indicated in this connection. By means of this probability it is possible to classify the individual case. The forecast is simulated by coincidental dividing of the data: the first part of the data is used for the explanation, the second for the forecast. With the comparison of the logistic regression with the neural nets, the superiority of neural nets in the explanation of "relapse" can be shown, since the neural nets are able to consider dependence between the explaining variables and according to that they offer a differentiated explanation. Their efficiency to predict "relapse" depends on the comparability of the distribution in the two coincidentally provided samples, the training data record for determining the explanation and the test case for the use of the explanation regarding the forecast. For optimal explanation and forecast neural nets are to be preferred to the logistic regression, since in the model with the better explanation also includes the potential for a usable better forecast. Moreover the model of the logistic regression is in fact a special case of the neural net, with a reduced complexity of the net.

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown. In this retrospective study, 601 patients were included. Patients received allo-SCT in CR1, CR2, CR >2 or in advanced disease in 69%, 15%, 2% and 14% of cases, respectively. With an overall follow-up of 58 months, 523 patients received a TBI-based regimen, whereas 78 patients received a chemotherapy-based regimen including IV busulfan-cyclophosphamide (IV Bu-Cy) (n=46). Unlike patients aged ⩾35 years, patients aged <35 years who received a TBI-based regimen displayed an improved outcome compared with patients who received a chemotherapy-based regimen (5-year leukemia-free survival (LFS) of 50% for TBI versus 18% for chemo-only regimen or IV Bu-Cy regimens, P=10(-5) and 10(-4), respectively). In multivariate analysis, use of TBI was associated with an improved LFS (hazard ratio (HR)=0.55 (0.34-0.86), P=0.01) and overall survival (HR=0.54 (0.34-0.87), P=0.01) in patients aged <35 years. In conclusion, younger adult patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia.

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

Imatinib therapy prior to myeloablative allogeneic stem cell transplantation.

It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.