We assessed incidence and risk factors of cardiovascular events in 265 patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) between 1980 and 2000 and who survived at least 2 years. Results were compared with a cohort of 145 patients treated during the same period with autologous HSCT. The median age of patients with allogeneic HSCT at last follow-up was 39 years, and median follow-up was 9 years. Eighteen (6.8%) patients after allogeneic and 3 (2.1%) patients after autologous HSCT experienced an arterial event. The cumulative incidence of first arterial event after allogeneic HSCT was 22.1% (95% CI, 12.0-40.9) at 25 years. The cumulative incidence 15 years after allogeneic HSCT was 7.5% as compared with 2.3% after autologous HSCT. Adjusting for age, risk of an arterial event was significantly higher after allogeneic HSCT (RR 6.92; P ‫؍‬ .009). In multivariate analysis, allogeneic HSCT (RR: 14.5; P ‫؍‬ .003), and at least 2 of 4 cardiovascular risk factors (hypertension, dyslipidemia, diabetes, obesity) (RR:

BackgroundLong-term outcome after hematopoietic stem cell transplantation including late transplantrelated events is of increasing interest. The aim of this study was to evaluate the incidence of cardiovascular events after allogeneic HSCT and to search for their risk factors.

SummaryWe explored the feasibility of unrelated donor haematopoietic stem cell transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then compared to matched historical controls who had undergone first-line therapy with a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the upfront cohort was 96 AE 4% compared to 91 AE 3% in the MSD controls (P = 0Á30) and 94 AE 3% in the IST controls (P = 0Á68) and 74 AE 9% in the unrelated donor HSCT post-IST failure controls (P = 0Á02).The 2-year event-free survival in the upfront cohort was 92 AE 5% compared to 87 AE 4% in MSD controls (P = 0Á37), 40 AE 7% in IST controls (P = 0Á0001) and 74 AE 9% in the unrelated donor HSCT post-IST failure controls (n = 24) (P = 0Á02). Outcomes for upfront-unrelated donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched unrelated donor HSCT is a novel treatment approach and could be considered as first-line therapy in selected paediatric patients who lack a MSD.

SummaryThis study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0Á18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0Á001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0Á017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0Á73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0Á0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0Á0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.

As risk for secondary breast cancer is elevated among cancer survivors treated with conventional therapy, we sought to determine the risk among 3337 female 5-year survivors who underwent an allogeneic hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center or at one of 82 centers reporting to the European Bone Marrow Transplant Registry. Risk was calculated using standardized incidence ratios (SIRs), and risk factors were evaluated with a multivariable Cox proportional hazards model. Fifty-two survivors developed breast cancer at a median of 12.5 (range: 5.7-24.8) years following HCT (SIR ‫؍‬ 2.2). Twenty-five-year cumulative incidence was 11.0%, higher among survivors who received total body irradiation (TBI) (17%) than those who did not receive TBI (3%). In multivariable analysis, increased risk was associated with longer time since transplantation (hazard ratio [ IntroductionHematopoietic cell transplantation (HCT) is now successfully used in the treatment of malignant and nonmalignant diseases, resulting in a growing cohort of long-term survivors. Accompanying this survivorship has been the development of adverse long-term outcomes, including subsequent malignant neoplasms (SMNs). 1 New cancers of solid organs have been reported among HCT survivors, with an excess risk for cancers of the liver, thyroid, brain, bone, connective tissue, cervix, oral cavity, and skin. [2][3][4][5][6][7][8][9][10][11] Survivors of cancer treated with conventional chemoradiotherapy are at an increased risk for the development of subsequent breast cancer. [12][13][14][15][16][17][18][19][20][21] We therefore hypothesized that survivors of HCT would also have an excess risk for subsequent breast cancer, with the risk modified by the use of total body irradiation (TBI) and the occurrence of chronic graft-versus-host disease (GVHD), as has been reported for other solid organ cancers following HCT. [4][5][6]8,9 Methods PatientsData were available for 3337 female patients who underwent transplantation at the Fred Hutchinson Cancer Research Center (FHCRC, n ϭ 968) or affiliated hospitals in Seattle or at one of 82 centers reporting to the European Group of Bone and Marrow Transplantation (EBMT, n ϭ 2369) between November 1969 and December 2000 and who survived at least 5 years after HCT. Additional participants in the EBMT Study Group may be found in Document S1 (available on the Blood website; see the Supplemental Materials link at the top of the online article.) Patient follow-up and data collectionClinical surveillance of patients who underwent HCT was approved by the FHCRC Institutional Review Board and by the review boards at each of the participating institutions reporting to the EBMT. Informed consent was provided according to the Declaration of Helsinki. Patient characteristics, HCT treatment regimens, and clinical outcome data were collected prospectively and stored in the FHCRC and the EBMT databases. At the FHCRC, a long-term follow-up department has been in place for more than 30 years to capt...

Bone marrow examination (BME) represents an essential tool for diagnosis and monitoring of haematological disorders. It remains associated with morbidity and discomfort; repeat examinations are frequent. We made a single-centre prospective survey on 700 BME between July 2007 and July 2008 with a structured anonymized questionnaire for patients undergoing and physicians performing BME, which includes at our institution always aspiration and trephine. All procedures were performed according to institutionalised standard operating procedures; 412 patients' (58.9%) and 554 physicians' (79.1%) questionnaires were returned. Pain was the only procedure-related complication; no pain was reported in 149 (36.7%), bearable pain in 242 (59.6%) and unbearable pain in 15 (3.7%) cases. Premedication associated complications were reported by 110 (32.7%) of the 336 (65.4%) patients with premedication before BME. None of these were > WHO grade 2; most frequently reported were tiredness (76 patients; 22.6%), dizziness (19 patients; 5.7%) and nausea (15 patients; 4.5%). Only two factors were significantly associated with unbearable pain: "pain during prior BME" (seven of 94 with versus one of 198 without previous pain; p < 0.01) and "information before BME" (four of 11 without versus 12 of 372 with adequate information before BME; p < 0.01). Inadequate information at any time showed a trend towards an association with unbearable pain (p = 0.08). No other factor was associated with unbearable pain. Good and adequate information appears to be the best way to reduce pain, even for a future BME.

ABSTRACTplantation (HSCT) is the preferred first-line treatment. 3,5

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