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In all, 651 from 680 centers in 48 countries reported 35 660 hematopoietic SCT (HSCT) in 32 075 patients (13 470 allogeneic (42%), 18 605 autologous (58%)) to the 2011 survey. Main indications were: leukemias; 10 113 (32%; 94% allogeneic); lymphoid neoplasias; non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasma cell disorders; 18 433 (57%; 12% allogeneic); solid tumours; 1573 (5%; 5% allogeneic); and non-malignant disorders; 1830 (6%; 92% allogeneic). There were more unrelated donors than HLA identical sibling donors (54% versus 39%); proportion of peripheral blood as stem cell source was 99% for autologous and 73% for allogeneic HSCT. Cord blood was only used in allogeneic transplants (6% of total). In the past 10 years, the overall number of transplants has increased by 53%. Allogeneic HSCT have doubled (from 7272 to 14 549) while, autologous have increased by 32% and continue to increase by about 1100 HSCT per year since 2001. In the past 2 years, an increase of >2000 HSCT per year was seen. Transplant activity is shown by team size. For allogeneic HSCT, we show use of reduced-intensity conditioning versus myeloablative conditioning across Europe and use of post-transplant donor lymphocyte infusions with considerable variation across different countries. [ABSTRACT FROM AUTHOR]

Among the novel biological therapeutics that will increase our ability to cure human cancer in years to come, adoptive cellular therapy is one of the most promising approaches. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. The results obtained with tumor-infiltrating lymphocytes therapy for melanoma, and virus-specific CTLs for EBV-associated malignancies are encouraging in terms of both ability to obtain clinical benefit and limited toxicity profile. In both settings, objective responses were obtained in at least 50% of treated patients. However, improvements to the clinical protocols, in terms of better patient selection and timing of administration, as well as cell product quality and availability, are clearly necessary to further ameliorate outcome, and logistical solutions are warranted to extend T-cell therapy beyond academic centers. In particular, there is a need to simplify cell production, in order to decrease costs and ease preparation. Promising implementations are underway, including harnessing the therapeutic potential of T cells transduced with TCRs directed against shared tumor antigens, and delineating strategies aimed at targeting immune evasion mechanisms exerted by tumor cells. [ABSTRACT FROM AUTHOR]

A total of 654 centers from 48 countries were contacted for the 2010 survey. In all, 634 centers reported a total of 33 362 hematopoietic SCT (HSCT) with 30 012 patients receiving their first transplant (12 276 allogeneic (41%) and 17 736 autologous (59%)). Main indications were leukemias: 9355 (31%; 93% allogeneic), lymphoid neoplasias specifically Non Hodgkin's lymphoma, Hodgkin's lymphoma and plasma cell disorders: 17 362 (58%; 12% allogeneic), solid tumors: 1585 (5%; 6% allogeneic) and non-malignant disorders: 1609 (6%; 88% allogeneic). There were more unrelated donors than HLA-identical sibling donors (53% versus 41%); the proportion of peripheral blood as stem cell source was 99% for autologous and 71% for allogeneic HSCT. Cord blood was primarily used in allogeneic transplants (6% of total) with three autologous cord blood HSCT being reported. The number of transplants has increased by 19% since 2005 (allogeneic 37% and autologous 9%) and continued to increase by about 1100 HSCT per year since 2000. Patterns of increase were distinct and different. The data show the development of transplantation in Europe since 1990, with the number of patients receiving a HSCT increasing from 4200 to over 30 000 annually. The most impressive trend seen is the steady increase of unrelated donor transplantation, in parallel to the availability of unrelated donors through donor registries. [ABSTRACT FROM AUTHOR]

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Quality of life (QoL) in medicine and in oncology is an accepted parameter for the evaluation of the benefit of treatments. Scientific methods exist to assess QoL measures in clinical trials. However, many components of the person that are properly humane and determine the patient’s attitude towards the disease are not measured by current criteria. Based on clinical experience, the author considers that a shift in knowledge and in doctors’ attitudes is required to also include non-measurable parameters in the doctor-patient relationship. [ABSTRACT FROM AUTHOR]

The European Group for Blood and Marrow Transplantation regularly publishes special reports on the current practice of haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published. HSCT today includes grafting with allogeneic and autologous stem cells derived from BM, peripheral blood and cord blood. With reduced-intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged, such as autoimmune disorders and AL amyloidosis for autologous HSCT and solid tumours, myeloproliferative syndromes and specific subgroups of lymphomas for allogeneic transplants. The introduction of alternative therapies, such as imatinib for CML, has challenged well-established indications. An updated report with revised tables and operating definitions is presented. [ABSTRACT FROM AUTHOR]

The role of 18FDG-PET/CT during follow-up of patients affected by Hodgkin's lymphoma (HL) in complete remission after treatment is not fully elucidated, since a wide use of 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) in this setting could be limited by a relative high rate of false-positive results. Herein, we summarize a retrospective analysis of 27 patients with Hodgkin's lymphoma in complete remission after the first-line (n = 20) or salvage (n = 7) therapy receiving serial 18FDG-PET/CT scans during follow-up. Out of 165 scans, 13 were suspected for relapse, which was confirmed in seven patients. All relapses were correctly identified by 18FDG-PET/CT positivity, with a 100% sensitivity; false-positive rate was 46% and negative predictive value was 100%. True-positive findings were mostly associated with multiple sites, subdiaphragmatic involvement, and/or previous sites of disease. According to our results, we conclude that performing routine PET/CT scan during follow-up of those patients who are at high risk of relapse would be advisable, although caution must be adopted when interpreting PET/CT results due to the relatively high rate of false-positive findings. If FDG abnormal uptake is present at multiple nodal sites, subdiaphragmatic lymph nodes, or previous sites of disease, histological verification of PET abnormal findings is warranted. [ABSTRACT FROM AUTHOR]

SCT from an HLA-compatible sibling donor is an adoptive immunotherapy for cytokine-refractory, metastatic clear-cell renal cell cancer (RCC). However, the recent introduction of targeted therapy compounds has reduced the interest in this therapeutic strategy. We have reanalyzed our series with the aim to assess long-term benefit from allografting. Twenty-five RCC patients received a reduced-intensity allograft from an HLA-identical sibling donor. All patients received a thiotepa, fludarabine and CY conditioning regimen, and a cyclosporine-based GVHD prophylaxis. Best response to allograft was evaluable in 24 patients: 1 CR, 4 PR, 12 minor response/stable disease, 7 progressive disease. One-year survival was 48%, and five-year survival was 20%. At a median observation time of 65 months, five patients are alive, one in CR, one in PR and three with stable disease. By multivariate analysis, C-reactive protein value before transplant, the number of CD34+ infused cells and disease status at day +90 significantly correlated with survival. Survival of patients at favorable/intermediate-risk according to the MSKCC score that underwent allografting was better in comparison to the survival predicted by historical controls. We conclude that 20% of cytokine-refractory RCC patients are alive long-term after allografting. Transplantation is able to induce long-term disease control in a fraction of relapsed RCC patients [ABSTRACT FROM AUTHOR]

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3–64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.Bone Marrow Transplantation (2008) 41, 537–545; doi:10.1038/sj.bmt.1705940; published online 17 December 2007 [ABSTRACT FROM AUTHOR]

The safety and efficacy of reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (SCT) for relapsed lymphomas remains unresolved. We conducted a prospective, multicentered, phase II trial. A total of 170 relapsed/refractory lymphomas received a RIC regimen followed by SCT from sibling donors. The primary study end point was non-relapse mortality (NRM). Histologies were non-Hodgkin's lymphomas (NHL) (indolent (LG-NHL), n=63; aggressive (HG-NHL), n=61; mantle cell lymphoma (MCL), n=14) and Hodgkin's disease (HD, n=32). Median follow-up was 33 months (range, 12–82). The results show that frequencies were as follows: cumulative NRM at 3 years, 14%; acute and chronic graft-versus-host disease (GVHD) 35 and 52%, respectively; 3-year overall survival (OS), 69% for LG-NHL, 69% for HG-NHL, 45% for MCL and 32% for HD (P=0.058); and 3-year relapse incidence, 29, 31, 35 and 81%, respectively (P<0.001). Relapse risk differed significantly at 3 years between follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL) (14 versus 46%, P=0.04). Molecular remission occurred in 94 and 40% (P=0.002) of patients with FL and CLL, respectively. On multivariate analysis, OS was influenced by chemorefractory disease (hazard ratio (HR)=3.6), diagnosis of HD (HR=3.5), and acute GVHD (HR=5.9). RIC allogeneic SCT is a feasible and effective salvage strategy in both indolent and aggressive NHLLeukemia (2007) 21, 2316–2323; doi:10.1038/sj.leu.2404822; published online 28 June 2007 [ABSTRACT FROM AUTHOR]

In October 2005, the second international meeting on allogeneic transplantation in solid tumors was convened in Stresa (Italy). The aim of this second meeting was to share clinical experiences of allografting in solid tumors, to discuss preclinical data on the mechanisms of graft-versus-tumor (GVT) effect, and to review methods for more efficacious transplant approaches. On the first day, the most recent results in cancer immunotherapy were reviewed; head-to head comparisons of clinical results achieved by standard therapy and by allografting in renal, breast, and ovarian cancer were presented. On the second day, GVT mechanisms and preclinical models were examined; anecdotal reports of a GVT effect in sarcoma, pancreatic cancer, prostate cancer, colorectal cancer and lung cancer were presented; new strategies for optimizing transplant outcome were discussed, including patient selection, tumor debulking, auto–allo approaches, selective T-cell depletion, targeting with monoclonal antibodies, use of killer cell immunoglobulin-like receptor-ligand mismatched natural killer cells. In conclusion, allografting in solid tumors is feasible with limited toxicities and transplant-related mortality; a GVT effect has been documented in many different solid tumors; targeting of the immune response to the tumor by new strategies and identification of the target antigen(s) of the GVT effect are promising areas of research.Bone Marrow Transplantation (2006) 38, 527–537. doi:10.1038/sj.bmt.1705479; published online 4 September 2006 [ABSTRACT FROM AUTHOR]

HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with high-dose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2+ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P=0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age 50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2+ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age 50 years or receiving multiple course of HDC should be considered at risk for CD.British Journal of Cancer (2006) 94, 1016–1020. doi:10.1038/sj.bjc.6603060 www.bjcancer.com Published online 28 March 2006 [ABSTRACT FROM AUTHOR]

We assessed mammaglobin (MMG) gene expression in bone marrow (BM) aspirates from patients with advanced breast cancer who had received a reduced-intensity conditioning and stem cell allografting, in order to detect a graft-versus-tumor effect on micrometastatic disease. Nine patients received a reduced-intensity conditioning with fludarabine, cyclophosphamide, and thiotepa, followed by peripheral blood allografting from HLA-identical sibling donors. Nested RT-PCR analysis with sequence-specific primers for MMG was carried out on a monthly basis on BM samples. Three patients had MMG-positive BM, four patients had MMG-negative BM before allografting, and two were undetermined. In two patients, a clinical response after allografting (partial remission) occurred concurrently with the clearance of MMG expression, at a median of 6 months after allografting, following immune manipulation. In two patients, a prolonged stable disease and negative MMG expression occurred after day +360 from allografting. In two patients, progression of the disease was associated with MMG RT-PCR changing from negative to positive. In one case, a disease response occurring after donor lymphocyte infusion and grade II acute GVHD was heralded by negativization of MMG expression. Although preliminary, these data suggest that a graft-versus-breast cancer effect is detectable on micrometastatic BM disease.Bone Marrow Transplantation (2006) 37, 311–315. doi:10.1038/sj.bmt.1705248; published online 9 January 2006 [ABSTRACT FROM AUTHOR]

Mobilized blood CD34+ cells from cancer patients were ex vivo infected by a recombinant adenovirus vector carrying an alkaline phosphatase gene, whose expression is evaluable by flow cytometry. A mean of 40% CD34+ cells were infected by the vector, with high levels of expression of the transgene. Among attempts to improve infection efficiency by manipulating culture conditions, only reinfection by the same vector achieved a 10% increase of transgene expression. Transduced CD34+ cells were induced to differentiate along the myeloid and the dendritic lineage, and in either case AP+ cells were detectable among the differentiated cell population. We conclude that adenovirus vectors may be useful tools for gene transduction into mobilized blood CD34+ cells, particularly for those applications in which high transgene expression for limited periods of time is required. [ABSTRACT FROM AUTHOR]

Various restriction enzymes digest human highly repeated homogeneous DNA to discrete fragments, some of which are present in the male and absent in the female. The male specific 2.4 kilobase HaeIII fragment corresponds to human male satellite DNA IV. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding combination of allograft with mTOR inhibitors for metastatic renal cell cancer.

Presents a correction to the article 'Benefits of blood cell transplant cryopreservation with oxypolygelatine (Gelifundol) plasma substitute,' by M. di Nicola, S. Siena et al., from the 1996 issue of 'Bone Marrow Transplantation.'