Leukaemic transformation of donor cells in a patient receiving a second allogeneic bone marrow transplant for severe aplastic anaemia

Allogeneic blood or bone marrow transplantation is a successful treatment for leukaemia and severe aplastic anaemia (SAA). Graft rejection following transplantation for leukaemia is a rare event but leukaemic relapse may occur at varying rates, depending upon the stage of leukaemia at which the transplant was undertaken and the type of leukaemia. Relapse is generally assumed to occur in residual host cells, which are refractory to, or escape from the myeloablative conditioning therapy. Rare cases have been described, however, in which the leukaemia recurs in cells of donor origin. Lack of a successful outcome of blood or bone marrow transplantation for severe aplastic anaemia (SAA), however, is due to late graft rejection or graft-versus-host disease. Leukaemia in cells of donor origin has rarely been reported in patients following allogeneic bone marrow transplantation for SAA. This report describes leukaemic transformation in donor cells following a second allogeneic BMT for severe aplastic anaemia. PCR of short tandem repeats in bone marrow aspirates and in colonies derived from BFUE and CFU-GM indicated the donor origin of leukaemia. Donor leukaemia is a rare event following transplantation for severe aplastic anaemia but may represent the persistence or perturbation of a stromal defect in these patients inducing leukaemic change in donor haemopoietic stem cells.

Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/- Ida) and second allogeneic stem cell transplant

Acute leukaemias in relapse after allogeneic stem cell transplantation (SCT) respond poorly to donor leucocyte infusions (DLI) compared with chronic myeloid leukaemia (CML), at least in part because of faster disease kinetics. Fludarabine-containing 'non-myeloablative' chemotherapy followed by further allo SCT may offer more rapid and effective disease control. We report 14 patients with relapse after allo SCT for acute leukaemia [seven acute myeloid leukaemia (AML), five acute lymphoblastic leukaemia (ALL)] or refractory anaemia with excess blasts in transformation (RAEB-t, n = 2) treated with fludarabine, high-dose cytosine arabinoside (ara-C) and granulocyte colony-simulating factor (G-CSF) with (n = 10) or without (n = 2) idarubicin (FLAG +/- Ida) or DaunoXome (FLAG-X) (n = 2) and second allo SCT from the original donor. Donors were fully human leucocyte antigen (HLA) -matched in 13 cases with a single class A mismatch in one. Actuarial overall survival was 60% and disease-free survival was 26% at 58 months. Remissions after the second SCT were longer than those after the first bone marrow transplantation (BMT) in eight of the 13 assessable patients to date. Haematopoietic recovery was rapid. Transplants were well tolerated with no treatment-related deaths. The major complication was graft-versus-host disease (GvHD, acute >/= grade II-2 cases, chronic - eight cases, two limited, six extensive) although there have been no deaths attributable to this. FLAG +/- Ida and second allo SCT is a safe and useful approach and may be more effective than DLI in the treatment of acute leukaemias relapsing after conventional allo SCT.

Successful bone marrow transplant for Fanconi anaemia in transformation

We present a patient who was diagnosed as suffering from Fanconi anaemia at the age of 36 years. At the time of diagnosis his bone marrow showed features of pre-leukaemic transformation. He received an allogeneic bone marrow transplant (BMT) from his HLA-identical sibling. The post-transplant course was unremarkable with evidence of trilineage engraftment at day +32 and no acute or chronic GVHD. He is well with sustained engraftment and no haematological evidence of Fanconi anaemia 18 months post-transplant.

Tacrolimus is not associated with gingival overgrowth in renal transplant patients

BACKGROUND: Cyclosporin A is used extensively to prevent the rejection of allogenic renal transplants. However, it is associated with a variety of undesirable side effects including gingival overgrowth. Tacrolimus (FK506), has been marketed as an effective alternative immunosuppressant to cyclosporin A and recent subjective reports suggest patients taking it complain infrequently of gingival problems. This clinical investigation was undertaken to confirm whether or not tacrolimus adversely affected the gingival health of renal transplant recipients.

METHODS: Renal transplant patients (RTPs) under the care of the Renal Transplantation Service at the Manchester Royal Infirmary, who had received a renal allograft at least 18 months earlier, were recruited for this study. All but one of the RTPs had been taking tacrolimus since transplantation. The other had commenced tacrolimus therapy two months after receiving her allograft. A hospital based control group was recruited from non transplanted individuals attending the Turner Dental School, Manchester. Each patient underwent a detailed dental assessment and had dental impressions taken. The extent of gingival overgrowth was determined from plaster models.

RESULTS: 25 renal transplant recipients and 26 control patients were included in the study. None of the individuals in either the tacrolimus or control groups had clinically significant overgrowth. The patients in the tacrolimus group with the highest overgrowth scores were those also taking calcium antagonists as treatment for hypertension.

CONCLUSION: This study demonstrates that tacrolimus has no adverse effects on the gingival tissues and thus has potential as an alternative immunosuppressant for individuals susceptible to developing cyclosporin A-induced gingival overgrowth.

The influence of transforming growth factor-beta1 gene polymorphisms on the severity of gingival overgrowth associated with concomitant use of cyclosporin A and a calcium channel blocker

The purpose of this study was to determine whether the prevalence and severity of gingival overgrowth in renal transplant recipients concomitantly treated with cyclosporin and a calcium channel blocker was associated with functional polymorphisms within the signal sequence of the transforming growth factor-(TGF)beta1 gene.

Association of Functional Heme Oxygenase-1 Gene Promoter Polymorphism with Renal Transplantation Outcomes

Heme oxygenase-1 (HO-1) is a cytoprotective molecule and increased expression in experimental transplant models correlates with reduced graft injury. A functional dinucleotide repeat (GT)n polymorphism, within the HO-1 promoter, regulates gene expression; a short number of repeats (S-allele

Is screening for Factor V Leiden and Prothrombin G20210A Mutations in Renal Transplantation worthwhile? Results of a large single-center U.K. study

This single center study is the largest series of renal transplant recipients and donors screened for the commonest prothrombotic genotypes. A total of 562 transplant recipients and 457 kidney donors were genotyped for the factor V Leiden and prothrombin G20210A mutations. The prevalence of heterozygous factor V Leiden was 3.4% and 2.6% and prothrombin G20210A was 2.0% and 1.1% in recipients and donors, respectively, similar frequencies to that of the general U.K. population. The 30-day and 1-year graft survival rates in recipients with thrombophilic mutations were 93% and 93%, compared with 88% and 82% in patients without these mutations (log-rank P =0.34). Thrombophilia in recipients (odds ratio 0.55; confidence interval 0.06-2.29; P =0.56) or in donors (odds ratio 1.53; confidence interval 0.27-5.74; P =0.46) did not correlate with graft loss at 30 days after transplantation. In contrast to recent reports, this study did not demonstrate an association between thrombophilia and renal allograft loss, and routine screening is not recommended.