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Allogeneic haematopoietic cell transplantation is an established curative treatment modality for patients with malignant and non-malignant haematological disorders. Since the first related umbilical cord blood transplant (UCBT) in 1988, the use of UCB as a stem cell source for transplantation has become a standard practice in many countries, with approximately 8000 such transplants having been performed worldwide to date.

AlloSCT is a potentially curative procedure for haematological malignancies and marrow failure syndromes. However, unlike leukaemia and lymphoproliferative disorders, AlloSCT has yet to find its place in the clinical management of patients with multiple myeloma. AlloSCT in multiple myeloma is associated with a high procedure-related mortality (TRM up to 35%) when full-intensity conditioning is used and only up to 36% of cases show long-term disease-free survival. The introduction of reduced intensity conditioning AlloSCT, more recently following an autologous SCT, has reduced the TRM to

Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous subset of lymphomas with a poorer prognosis compared with B-cell lymphomas. We conducted a retrospective study of 82 patients who received high-dose therapy for PTCL (autologous SCT (ASCT) N=64; allogeneic SCT (Allo-SCT) N=18). With a median follow-up from ASCT of 37 months from transplant, 33 patients were alive; 20 died of progressive disease, 10 died from non-relapse mortality (NRM) with 1 unknown cause. Three-year overall survival (OS) and progression-free survival (PFS) were 53% (95% confidence interval (CI) 42, 67) and 50% (95% CI 39, 64), respectively. Factors significantly affecting OS and PFS on univariate analysis were histological subtype and chemotherapy sensitivity. In a multivariate analysis, the only factor with significant impact was chemotherapy sensitivity. After a median follow-up from Allo-SCT of 57 months, five patients were alive; five died of progressive disease and eight died from NRM. The 3-year OS and PFS were 39% (95% CI 22, 69) and 33% (95% CI 17, 64), respectively, and the 3-year relapse rate was 28% (95% CI 6, 50). These results demonstrate that high-dose chemotherapy with autologous stem cell rescue has a substantial role in the management of T-cell lymphoma. The use of full-intensity allogeneic transplantation is limited by high transplant-related mortality, and exploration of reduced intensity regimens is warranted.

The use of reduced intensity conditioning (RIC) with alemtuzumab is associated with a higher rate of cytomegalovirus (CMV) reactivation than RIC without alemtuzumab,1 especially when combined with fludarabine.2 Alemtuzumab, used as in vivo T-cell depletion, has a long plasma half-life, resulting in prolonged lymphopaenia. In 16 patients receiving allogeneic stem cell transplantation (allo-SCT) with in vivo alemtuzumab, the half-life was estimated at 15–21 days with a median total lymphocyte count (TLC) at 6 months of only 0.5 × 109/l.3 Morris et al.4 reported lympholytic concentrations of alemtuzumab for 56 days after RIC in patients who were treated with 100 mg in vivo alemtuzumab (n=10).4 A sustained recovery of median TLC to >1 × 109/l was reached by 4 months in the myeloablative conditioning (MAC) group but not until 9 months in the RIC group. The higher rate of infective complications (for example, CMV and adenovirus) reported in T-cell-depleted RIC has, therefore, been attributed to delayed immune reconstitution.

EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50-65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had 10 000 and 40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12-0.74); P=0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12-2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo-SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed.

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.

Myeloablative allo-SCT decreases relapse incidence (RI) in ALL. Reduced intensity conditioning (RIC) may extend allo-SCT to older and less fit patients. Sixty-nine ALL patients reported to the BSBMT underwent fludarabine-based RIC allo-SCT, 38 from unrelated donors (UD). Forty-four patients received alemtuzumab. ALL was in CR in 64 patients (93%). This was a second or third SCT in 23 patients. Two-year OS and PFS were 36% and 32%, respectively. In multivariate analysis male recipients demonstrated better OS and PFS (hazard ratio (HR) = 0.42, P = 0.008 and HR = 0.45, P = 0.012, respectively). Two-year TRM was 29%: higher with younger age (HR = 0.97/year, P = 0.041), female recipient (HR = 2.55, P = 0.049) and increasing grade of acute GVHD (HR = 1.87, P = 0.001). Two-year RI was 38% and was lower in patients with acute and chronic GVHD (HR = 0.62 per increasing grade, P = 0.035 and HR = 0.52, P = 0.025, respectively). Long-term ALL-free survival is achievable following fludarabine-based RIC allo-SCT. The association between GVHD and decreased RI suggests the presence of a GVL effect.

The clinical course of 2009 H1N1 influenza in Allo-SCT patients is unknown. Data were collected in the UK from October 2009 to April 2010 on laboratory-confirmed cases of H1N1 influenza in Allo-SCT recipients. H1N1 infection was diagnosed in 60 patients, median age 42 years, at a median of 10 months post-SCT. Twenty-one patients (35%) developed pneumonia and nine (15%) required admission to intensive care units. Actuarial mortality was 7% at 28 days and 19% 4 months post-diagnosis of 2009 H1N1 influenza. Increasing age and pre-existing lung disease were risk factors for pneumonia (P=0.006 and 0.037, respectively); older age was a risk factor for death (P=0.012). Morbidity and mortality from 2009 H1N1 influenza in SCT patients exceeds that of immunocompetent patients, but parallels that in other critically ill hospitalised cohorts; the elderly and those with chronic pulmonary disease are at greatest risk.

Prognostic impact of serum ferritin concentration on survival following reduced-intensity conditioned allogeneic haemopoietic SCT

Fifty-one patients with primary myelofibrosis (PMF) received allogeneic haematopoietic stem cell transplants from related (n=33) or unrelated (n=18) donors. Twenty-seven patients, 19-54 years old, were prepared with myeloablative regimens including CY plus BU (n=4) or TBI (n=23). Twenty-four patients, 40-64 years old, received reduced-intensity conditioning (RIC) regimens. All RIC regimens contained fludarabine, combined with melphalan (n=19) or BU (n=5), and alemtuzumab or anti-thymocyte globulin (ATG) in the majority (n=19). Four patients (17%) in the RIC group had primary graft failure. Previous splenectomy reduced time to engraftment in the RIC group (13 versus 20 days; P=0.008). For MA and RIC groups, respectively, at 3 years, overall survival rates were 44 and 31% (P=0.67), progression-free survival 44 and 24% (P=0.87), and actuarial relapse rates 15 and 46% (P=0.06). Non-relapse mortality at 3 years was 41% for the myeloablative and 32% for the RIC group. Acute GVHD occurred in 29 and 38% of patients in the myeloablative and RIC groups, respectively. Extensive chronic GVHD developed in 30 and 35% of evaluable patients, respectively.

ATL-104 is a potent mitogen for epithelial cells of the gastrointestinal tract. In animal models, ATL-104 aids regeneration of the gastrointestinal tract after treatment with chemotherapeutic agents. The effect of ATL-104 on mucositis in patients requiring high-dose melphalan or BEAM before peripheral blood SCT (PBSCT) was investigated in a randomized, placebo-controlled, double-blind, two-part study. Patients were randomized to ATL-104 (50, 100 or 150 mg) or placebo once daily for 3 days before chemotherapy and 3 days after PBSCT. Part one of the study was a dose-escalation design; part two was a parallel group design using all three ATL-104 doses. Patients were followed up for 28 days post-treatment. Severity of signs and symptoms were assessed and used to calculate scores for standard toxicity rating scales (WHO, Western Consortium for Cancer Nursing Research (WCCNR)). Sixty-three patients were treated. Treatment with ATL-104 substantially reduced the median duration of severe oral mucositis (WHO grade 3 or 4) compared with placebo (median duration: ATL-104 groups 2 or 3 days, placebo 10.5 days). The effect of ATL-104 on the incidence of severe oral mucositis was inconclusive. Similar results were obtained using the WCCNR Scale. Adverse events (AEs) were predominantly mild or moderate in intensity. Gastrointestinal AE were most common.

We have demonstrated previously that cord blood CD133(+) cells isolated in the G(0) phase of the cell cycle are highly enriched for haematopoietic stem cell (HSC) activity, in contrast to CD133(+)G(1) cells. Here, we have analysed the phenotype and functional properties of this population in more detail. Our data demonstrate that a large proportion of the CD133(+)G(0) cells are CD38 negative (60.4%) and have high aldehyde dehydrogenase activity (75.1%) when compared with their CD133(+)G(1) counterparts (13.5 and 4.1%, respectively). This suggests that stem cell activity resides in the CD133(+)G(0) population. In long-term BM cultures, the CD133(+)G(0) cells generate significantly more progenitors than the CD34(+)G(0) population (P0.001) throughout the culture period. Furthermore, a comparison of CD133(+)G(0) versus CD133(+)G(1) cells revealed that multilineage reconstitution was obtained only in non-obese diabetic/SCID animals receiving G(0) cells. We conclude that CD133(+) cells in the quiescent phase of the cell cycle have a phenotype consistent with HSCs and are highly enriched for repopulating activity when compared with their G(1) counterparts. This cell population should prove useful for selection and manipulation in ex vivo expansion protocols.

Increasing demand on the apheresis service makes efficient harvesting of peripheral blood stem cells (PBSCs) essential. A total of 168 adult patients with haematological malignancy were primed using low-moderate dose cyclophosphamide (1.5-3 g/m(2)) with G-CSF 5-10 microg/kg per day. Harvesting was booked and peripheral blood (PB) counts first checked between 6 and 10 days post-priming. One hundred and thirty (77%) patients harvested successfully (total harvest yieldor =2 x 10(6) CD34(+)/kg) and the median PBSC collection per procedure was 2.18 x 10(6)/kg (range 0.1-14.5). Only more lines of prior chemotherapy predicted failure to harvest in multivariate analysis (P=0.003). The PB CD34(+) cell count correlated significantly with harvest yield (r=0.8448, P0.0001). A PB CD34(+) countor =10/microl predicted a collection ofor =2 x 10(6)/kg (positive-predictive value of 61%, negative-predictive-value 100%). Patients first attending day 9 required significantly fewer visits to achieve a successful harvest than those first attending days 6-8 without increasing the risk of failure. No significant difference in failure rates, number of days attending and total harvest yield was found between days 9 and 10 attendees. Collection from day 9 may however enable higher target yields to be achieved. PB CD34(+) count monitoring should commence and harvesting booked from day 9 to optimize both the harvest and the efficiency of the PBSC harvesting service.

Unsuccessful stem cell remobilization for autologous transplantation is predicted by renal impairment and a stem cell yield 0.5 × 10 6 CD34 + cells/kg at first mobilization

Voriconazole or itraconazole for antifungal prophylaxis in patients with grade II-IV acute or extensive chronic graft-versus-host disease