We reviewed the incidence and risk factors for EBVrelated post-transplant lymphoproliferative disorder (EBV-PTLD) in 89 patients with acquired aplastic anaemia (AAA) receiving allogeneic transplants between 1989 and 2006. The overall incidence of EBV-PTLD was 6.3% (5/89) with no cases in those receiving an allograft for constitutional BM failure syndromes (n ¼ 30) during the same period. There was no impact of age, gender, donor status, CMV seropositivity, GVHD and graft cell dose on the occurrence of PTLD. Although both reduced intensity conditioning (RIC) and the prior use of antithymocyte globulin (ATG), as immunosuppressive therapy (IST), were identified as the risk factors for PTLD, only prior use of ATG strongly influenced the development of PTLD with an incidence of 13.38±5.6% (5/43), compared with none in those not exposed to ATG before transplantation (P ¼ 0.01) with a relative risk of 10.39 for each course of prior ATG. This is the first study in patients with AAA documenting that those receiving multiple prior courses of ATG are at the highest risk of developing EBV-PTLD.

Warfarin reversal is frequently required in day to day haematology practice. Prothrombin complex concentrates (PCC) have replaced fresh frozen plasma as the agent of choice in warfarin reversal due to its safety profile. Ideal dose of PCC is still not known and many centres have local guidelines on using the product. We have successfully used PCC (Beriplex) at a fixed dose in our hospital, but we still need randomised control trials to identify the ideal dose of PCC which can result in rapid reversal of warfarin with minimum risk of thrombosis.

Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities.

Rituximab (chimeric anti-CD20 monoclonal antibody) has been reported to be effective in various autoimmune conditions, especially in autoimmune cytopenias, but there are few reports of its use in paediatric population with underlying immunodeficiency states. We report three cases of autoimmune cytopenias (Evan’s syndrome in DiGeorge syndrome, autoimmune thrombocytopenia in a HIV positive patient and lastly autoimmune thrombocytopenia in a post liver transplant patient) where rituximab was effective in reversing the cytopenias. First patient (11yrs) had DiGeorge syndrome which was complicated by Evan’s syndrome. It was treated with multiple courses of steroids and immunosuppressive agents, with resultant recurrent systemic bacterial and fungal infections. She had rituximab as a last resort, which resulted in sustained improvements in her Haemoglobin and platelet count. Second patient (12yrs) was diagnosed with HIV in 1993. She had sudden onset Intra-cranial bleed as a result of immune thrombocytopenia. She was treated with Intravenous immunoglobulin (IVIg) and subsequently with prednisolone with no response. She however responded to rituximab and then went on to have rituximab for a further 2 courses, each 12 months apart. The third patient (14yrs) had auxiliary liver transplant in 2002. He developed immune thrombocytopenia and neutropenia in which remission was sustained only for a maximum of 6 weeks following IVIg. As he was already on immunosuppression, he was given rituximab to which he has had a sustained remission. Side effects: The patient with DiGeorge syndrome had recurrent chest infection which was thought to be due to aspiration as a result of her hiatus hernia. The other patients did not have major side-effects. Immunoglobulin levels in all three patients were in normal range. Thus, in our experience rituximab is a useful adjunct in management of autoimmune cytopenias with an underlying immunodeficiency state and should be considered early in steroid refractory cases, as it leads to sustained remissions in the blood counts. It is well tolerated without major infections in patients who are already immunosuppressed due to their immunodeficiency state and the fear of immuneparesis is not seen.

Previous reports of second allografts for relapsed leukaemia involved either children or young adults. However, the majority of myeloid leukaemias present in patients over 50 years of age. Lower TRM from Reduced Intensity Conditioning (RIC) HSCT has permitted older, previously not eligible patients to undergo sibling and unrelated donor allografts. However, therapeutic options are extremely limited when patients relapse. We report the outcome of second non-myeloablative transplant for these patients. A retrospective analysis of non-myeloablative allografts performed at Kings College identified 18 patients who received double RIC allografts for myeloid malignancies (de novo AML (3), MDS (10), CML (3) and Myelofibrosis (2)), of which 16 relapsed and 2 developed graft failure following the first transplant. The median age at second transplant was 55 years (R: 18–69). For the first allograft, 14 were conditioned with Fludarabine (150mg/m2)/Busulphan(8mg/Kg)/Campath (100mg) (FBC), 2 with Campath(80mg)/TBI(200cGy), and one with Busulphan (12.8mg/Kg)/Cyclophosphamide (200mg/Kg) and one with Etoposide (60mg/Kg)/TBI (1440cGy). For the second allograft, 6 received FBC, 4 FB, one Cyclophosphamide(120mg/Kg)/ALG(45mg/Kg), one Campath (100mg), 2 Mylotarg (18mg/m2), one Campath/TBI, one Fludarabine(150mg/m2)/Melphalan(140mg/m2) and 2 Fludarabine (150mg/m2)/Cytarabine(10g/m2)/GCSF( 1800ug/m2) (FLAG). 11 patients received stem cells from the same donor as the first transplant (9 Sib, 2 VUD) and 7 from different donors (2 Sib, 5 VUD). The median cell dose was 4.7 x 106 CD34 /Kg (R: 0.57 12.48). Sixteen patients underwent a second allograft for relapse and two for graft failure. Seven received HLA-matched VUD and 11 HLA-matched sibling donor cells. Day 100 DFS was 50% and TRM 33% with no significant difference between sibling and VUD allografts. Median neutrophil and platelets engraftment took 13 and 14 days respectively. Five patients died of relapse and 8 of of transplant-related complications (4 GvHD, 2 infection, 1 encephalopathy, 1 VOD). With a median follow up of 233 days (R: 4–1690 days), the Kaplan-Meier DFS reached a plateau of 26% (5 patients) at one year. Further analysis showed improved outcome for those who received a second transplant following remission induction (dysplastic and hypoplastic CR) compared to those transplanted in frank relapse. Four out of eight patients (50%) transplanted in CR remain disease-free, whereas only one out of eight (12.5%) transplanted with relapsed disease remains alive. Two patients transplanted for graft failure died. Of 13 deaths, 5 died of relapsed disease (38.5%), 4 of severe GVHD (30.8%) and infection, 2 (15.4%) of infection, one of encephalopathy (7.69%) and one of VOD (7.69%). Relapsed disease was the major cause of mortality despite a second allograft, followed by GvHD and infection. Despite the high TRM, the results suggest that second donor allograft performed for patients with myeloid malignancies who achieve CR confers a DFS of 50% at 1 year. The risks of a second non-myeloablative transplant for selected patients who achieve remission prior to procedure are acceptable in comparison to conventional treatment for relapsed disease post transplant, even in patients over 50 years of age.