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J Apperley

Publications and source records attributed to J Apperley.

At least 19 recordsLinked to original sources
PubMed2007

Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.

The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus-leukemia (GvL) effect exerted by donor T cells. CD4(+)CD25(high) regulatory T cells (T(regs)) have been shown to downregulate antitumor responses but their role on GvL has not been evaluated. We performed a cross-sectional study in which we enumerated and characterized CD4(+)CD25(high) T(regs) in the peripheral blood of CML patients undergoing allogeneic SCT. We documented higher frequencies of T(regs) in patients after transplant as compared to normal controls and newly diagnosed patients. The increment was particularly evident in patients who had received their SCT 18 months before. In vitro functional studies demonstrated that the T(regs) purified from SCT patients exhibited a more potent suppressive activity than T(regs) isolated from healthy volunteers. Patients in whom T(regs) numbers were higher than controls more than 18 months after SCT showed evidence of disease relapse. Although the increment in T(regs) might have an advantageous effect on graft rejection in the early phase post-transplant, our data suggest that T(regs) exert an inhibitory effect on GvL.

Adolescent↗
PubMed2006

LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed Hodgkin's lymphoma. We have analysed 67 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n=61) or primary refractory (n=6) Hodgkin's lymphoma. The 100-day treatment-related mortality was 3%. With a median follow-up of 67 months (range 3.3-161.0) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 68 and 64%, respectively. Probabilities for OS and PFS at 5 years for patients with chemosensitive relapse (n=40) were 81 and 78% versus 50 and 35%, respectively, for patients (n=27) with chemoresistant relapse (P=0.012 for OS, P=0.002 for PFS). In multivariate analysis mixed cellularity classical or lymphocyte-depleted classical histology subtype and haemoglobin level of 10 g/dl or less at the time of ASCT were identified as risk factors for worse OS, whereas stage III or IV disease at diagnosis and disease status at ASCT other than complete or partial remission predicted inferior PFS. LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.

Adolescent↗
PubMed2006

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe.

The Accreditation Subcommittee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published in 1996. Haemopoietic stem cell transplantation today includes grafting with allogeneic and autologous stem cells derived from bone marrow, 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, and solid tumours for allogeneic transplants. The introduction of alternative therapies has challenged well-established indications such as imatinib for chronic myeloid leukaemia. An updated report with revised tables and operating definitions is presented here.

Europe↗
PubMed2005

Use of intrathecal prophylaxis in allogeneic haematopoietic stem cell transplantation for malignant blood diseases: a survey of the European Group for Blood and Marrow Transplantation (EBMT).

SUMMARY: A survey was carried out among EBMT centres to describe the current practice concerning intrathecal (i.t.) prophylaxis in allogeneic stem cell transplantation for malignant diseases in patients with no central nervous system (CNS) manifestations of the disease at any time. A total of 90 centres reported their practice: 42 centres (47%) never used pre-transplant i.t. prophylaxis as part of the conditioning, whereas 48 centres (53%) gave i.t. prophylaxis to selected groups. The main indications were acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and lymphoma (53, 33, and 23% of all centres, respectively). Prophylaxis was usually given to all patients with ALL, but often restricted to high-risk patients in AML and lymphoma. Of the 90 centres, 29 (32%) gave prophylactic i.t. treatment after the transplantation, mainly for the same indications as pre-transplant. This survey illustrates the heterogeneity in the current practice of i.t. prophylaxis in allogeneic transplantation for malignant blood disorders in Europe. The documentation in the literature to support the use of i.t. prophylaxis as part of transplantation for malignant diseases in patients without preceding CNS involvement is sparse. Based on the rarity of isolated CNS relapse after allogeneic stem cell transplantation, EBMT does not recommend routine i.t. prophylaxis to patients without prior CNS involvement.

Antineoplastic Agents↗
PubMed2005

The impact of donor gender on outcome of allogeneic hematopoietic stem cell transplantation for multiple myeloma: reduced relapse risk in female to male transplants.

The impact of the donor gender on outcome in HLA-identical sibling donor hematopoietic stem cell transplantation for multiple myeloma was studied in a retrospective registry study of 1312 patients (476 male to male (M --> M); 334 female to male (F --> M); 258 male to female (M --> F); 244 female to female (F --> F) reported to the European Group for Blood and Marrow Transplantation (EBMT). The best overall survival (OS) from the time of transplantation was found in F --> F (median 41 months) with no significant difference between other groups (median 25 months in M --> M, 18 months in F --> M, 19 months in M --> F) despite a significantly higher nonrelapse mortality in F --> M. This was due to a significantly lower relapse rate (REL) in F --> M compared to all other groups. Before 1994, OS was poorer in F --> M than in M --> M, which improved to similarity from 1994 onwards (median 29 months in M --> M and 25 months in F --> M). The reduced REL contributed to this improvement in F --> M indicting a gender-specific graft vs myeloma effect. Therefore, a female donor is as good as a male one for male patients, while for female patients gender disparity is a negative factor for outcome.

Adult↗
PubMed2004

Autologous/syngeneic stem cell transplantation to treat refractory GvHD.

Severe graft-versus-host disease (GvHD) refractory to corticosteroids responds poorly to experimental treatment and is often fatal. Attempts have been made to 'rescue' such patients by transfusing autologous cells in order to ablate the lymphoid component of the graft or to introduce regulatory cells capable of suppressing the GvHD. Here, we report details of eight patients with severe grade III-IV acute GvHD (n=7) or extensive chronic GvHD (n=1) who after failing a median of four lines of treatment were then treated with either autologous or syngeneic nucleated cell transfusions. Patients received standard conditioning (n=3), low intensity (n=2) or no conditioning (n=3) before the rescue procedure. In four of the five patients who received some form of conditioning, mixed chimerism or complete recipient hematopoiesis was restored. The GvHD resolved in four patients, of whom one died subsequently of multiorgan failure and two died of leukemia; one is still alive. A fifth patient had transient improvement in GvHD, which recurred when the corticosteroids were reduced. Three patients obtained no benefit from the procedure. We conclude that 'rescue' by transfusion of autologous or syngeneic nucleated cells may be valuable to treat severe refractory GvHD; the best approach to conditioning remains to be defined.

Adult↗
PubMed2003

Strongyloidiasis pre and post autologous peripheral blood stem cell transplantation.

Hyperinfection with strongyloides stercolis occurs in the setting of chronic strongyloides infection in conjunction with immune suppression. Although malnutrition remains the major secondary cause worldwide in the developed world, iatrogenic immune suppression is an important precipitant. Autologous stem cell transplantation recipients are significantly immunocompromised albeit temporarily. Despite the increasing use of haemopoetic stem cell transplantation, hyperinfection with strongyloides has rarely been reported. We describe two cases of patients transplanted with chronic strongyloidiasis. In one case eradication therapy was given prior to the transplant which was uncomplicated. In the second case strongyloidiasis was diagnosed post transplant which was complicated by infection and respiratory compromise. Fatal hyperinfection subsequently developed after corticosteroid therapy was started for a disease progression in the CNS.

Aged↗
PubMed2003

Differences between graft product and donor side effects following bone marrow or stem cell donation.

We report graft product stem cell yields and donor safety results of a randomized multicenter study comparing allogeneic peripheral blood stem cell (PBSC) PBSC transplantation with BM transplantation. Matched HLA-identical sibling donors (n=329) were randomized to filgrastim-mobilized PBSC or bone marrow (BM) donation groups. Median yields per kg recipient weight of CD34(+) cells, T cells, and natural killer (NK) cells, respectively, were approximately two-fold, eight-fold, and greater than eight-fold in the PBSC group than in the BM group (CD34(+) cells, 5.8 x 10(6)/kg vs 2.7 x 10(6)/kg; T cells, 300.1 x 10(6)/kg vs 35.7 x 10(6)/kg; NK cells, 28.2 x 10(6)/kg vs 3.6 x 10(6)/kg; P<0.001 for each). In connection with the cell collection procedures, PBSC donors spent a shorter median time in hospital than BM donors (0 vs 2 days; median difference -2 days, 95% CI -2 to 2) and had fewer median days of restricted activity (2 vs 6 days; median difference -3 days, 95% CI -4 to 2). Overall, 65% of PBSC donors and 57% of BM donors reported at least one adverse event (AE), most of which were transient, mild-moderate in severity, and without clinical sequelae. PBSC donors experienced predominantly filgrastim-related AEs, while BM donors experienced predominantly harvest-related AEs.

Adolescent↗
PubMed2002

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe.

The Accreditation Sub-Committee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Major changes have occurred since the last report in 1998. Haemopoietic stem cell transplantation today includes allogeneic and autologous stem cells derived from bone marrow, 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, and solid tumours for allogeneic transplants. Other indications, such as autologous transplantation for breast cancer have been challenged. An updated report with revised tables and operating definitions is presented here.

Adult↗
PubMed2001

Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation.

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality after allogeneic stem cell transplantation (SCT), but cytotoxic T lymphocytes (CTL) may play a critical role in controlling CMV reactivation. Fluorescent HLA-peptide tetramers containing immunodominant peptides from CMV were used to prospectively monitor the recovery of CMV CTL in recipients of allogeneic transplants from siblings (n = 13) or unrelated donors (n = 11). In patients given allografts from a sibling when both the patient and donor were seropositive for CMV before SCT, recovery of CMV-specific CTL was rapid and reached up to 21% of all CD8(+) T cells. Early reconstitution of CMV-specific immunity was not observed if either the donor or recipient was seronegative for CMV. In recipients of transplants from volunteer unrelated donors, recovery of CMV-specific CTL was delayed in comparison to that in recipients of transplants from siblings and no CTL were observed within the first 100 days after SCT. CTL numbers were increased after episodes of CMV reactivation but were suppressed by prednisolone therapy. Recovery of CMV-specific CTL to levels greater than 10 x 10(6)/L was associated with protection from CMV disease. It was concluded that use of HLA-peptide tetramers to quantify CMV CTL is valuable for studying T-cell responses after allogeneic SCT. It should allow prediction of CMV reactivation in individual patients and assist in the development of adoptive T-cell immunotherapy.

Adolescent↗
PubMed2001

Parainfluenza virus 3 infection after stem cell transplant: relevance to outcome of rapid diagnosis and ribavirin treatment.

All 456 recipients of hemopoietic stem cell transplants (SCT) at the Hammersmith Hospital, London, from January 1990 through September 1996 were reviewed for parainfluenza virus (PIV) infections. Of the 24 (5.3%) PIV type 3 (PIV3)-infected patients, 10 had upper respiratory tract infection and all survived, but 8 of 14 with pneumonia died. A same-day immunofluorescence test diagnosed PIV3 infection in 20 (83%) of the 24 cases, but virus culture diagnosed only 10 (42%) of the 24 cases after a mean delay of 12 days. Eighteen PIV3-infected patients first received ribavirin at a median of 3 days after onset of symptoms, but, nevertheless, 2 patients shed PIV3 for 4 months. Six of 10 patients with pneumonia died despite early ribavirin therapy. The cause of death was not established by autopsy; 3 patients had concurrent infections, but in 3, only PIV3 was detected. The value of immunofluorescence testing for early diagnosis and treatment of PIV3 infection after SCT is demonstrated, but the outcome was not altered.

Adolescent↗
PubMed2001

Alpha-interferon maintenance treatment is associated with improved survival after high-dose treatment and autologous stem cell transplantation in patients with multiple myeloma: a retrospective registry study from the European Group for Blood and Marrow Transplantation (EBMT).

The purpose of this study was to evaluate the effect of alpha-IFN maintenance treatment after autologous stem cell transplantation (ASCT) for multiple myeloma in a retrospective registry analysis. 473 patients with multiple myeloma who received IFN maintenance treatment ASCT were compared with 419 patients who did not receive IFN-treatment. Patients who were evaluable for response and in complete or partial remission at 6 months after ASCT were eligible, after excluding patients with graft failure. Cox proportional hazards assumptions were checked and handled by stratification. The prognostic variables unevenly distributed between the two groups were statistically corrected for in the Cox analysis. 391 patients reached complete remission (CR) after ASCT (203 in the IFN group and 188 in the no-IFN group) and 501 were in partial remission (PR, IFN 270, no-IFN 231). Overall survival (OS) and progression-free survival (PFS) were significantly better in the IFN-group (OS, 78 vs 47 months, P = 0.007, and PFS, 29 vs 20 months, P = 0.006, respectively). The difference in OS and PFS was most strongly pronounced in the PR patients. 209 patients have died (IFN, 84; no-IFN, 125). Progressive myeloma was the cause of death in 94% of the IFN-treated patients and in 83% of the no-IFN group (P = NS). Thus, IFN maintenance treatment after ASCT was associated with better OS and PFS. Treatment seemed to be most beneficial in patients who did not achieve CR. The difference in median survival was as long as 2.5 years, and although part of this difference is attributable to differences in other prognostic factors, it might justify possible differences in quality-of-life due to adverse effects of interferon treatment.

Adolescent↗
PubMed2001

Immune haemolytic anaemia following T cell-depleted allogeneic bone marrow transplantation for chronic myeloid leukaemia: association with leukaemic relapse and treatment with donor lymphocyte infusions.

Immune haemolytic anaemia (IHA) is a recognised complication after allogeneic stem cell transplantation (SCT) and occurs more frequently if marrow cells have been subjected to T cell depletion (TCD). Among 58 consecutive patients who underwent TCD-allogeneic SCT from volunteer unrelated donors for the treatment of CML at the Hammersmith Hospital during a 3-year period (1 March 1996 to 28 February 1999) we identified nine cases of IHA. All patients had a strongly positive direct and indirect antiglobulin test and in eight patients the serological findings were typical of warm-type haemolysis often with antibody specificities within the Rh system. All nine cases had clinically significant haemolysis and were treated initially with prednisolone and immunoglobulin. The onset of IHA coincided with the occurrence of leukaemic relapse in six cases, and the presence of host haemopoiesis confirmed by lineage-specific chimerism in all four cases studied. Five patients received donor lymphocyte infusions (DLI); in three molecular remission and the restoration of full donor chimerism coincided with resolution of haemolysis. We conclude that in the context of leukaemic relapse, DLI is an effective therapy for IHA following allografts involving TCD.

Adolescent↗
PubMed2001

Genotypically nonidentical related donors for transplantation of patients with myelodysplastic syndromes: comparison with unrelated donor transplantation and autologous stem cell transplantation.

Transplantation with histocompatible identical siblings is a curative treatment for patients with myelodysplastic syndromes (MDS). Alternative treatments, such as transplantation with other family donors, are an option for patients without HLA-identical siblings. This study evaluated transplantation with genotypically nonidentical family donors and compared the results to those obtained with unrelated donors and autologous stem cell transplantation. Overall 3-year survival was 35% for the 79 patients transplanted using genotypically nonidentical donors, DFS was 31%, relapse risk 16%, and the treatment-related mortality (TRM) 62%. Patients transplanted using phenotypically identical family donors had a significantly superior survival and a lower TRM than patients transplanted with mismatched family donors. Age had no influence on the outcome of transplantation. The DFS of patients transplanted in early stage of the disease was 42% compared to 28% in patients transplanted with more advanced disease (P = 0.03). The results of transplantation with mismatched family donors were comparable to those obtained with unrelated donor transplantation. This suggests that nonidentical family donors may be considered if a fully matched unrelated donor is not available. The TRM of patients transplanted with nonidentical family donors is significantly higher than the TRM of patients transplanted with autologous stem cells. The disease-free survival of ASCT is not inferior to allogeneic transplantation using nonidentical family donors, and the intensity of the treatment is much lower. The choice of ASCT or alternative donor transplantation must be influenced by the age of the patient and the risk of relapse. For patients under the age of 20 years the treatment of choice may indeed be an alternative donor transplantation.

Adolescent↗
PubMed2001

Stem cell transplantation for chronic myeloid leukaemia: the role of infused marrow cell dose.

INTRODUCTION: Allogeneic stem cell transplantation is a potentially curative option for patients with CML. The optimal donor is an HLA-identical sibling but transplants using unrelated volunteers can also be successful. The factors influencing survival after allogeneic SCT for CML are reasonably well defined. Recently however, the Seattle group have emphasised the influence of a high marrow cell dose on outcome following volunteer unrelated donor SCT for high risk acute leukaemia. MATERIALS AND METHODS: We have sought to define factors impacting on transplant related mortality (TRM) in a population of CML patients after allografting with matched sibling or alternative stem cell donors at a single centre over a 20-year period, with emphasis on infused marrow cell dose. Factors entered into a multivariate analysis were: recipient age, recipient CMV serostatus, disease phase, donor sex, cell dose and frequency of CTLP reactivity. RESULTS: In multivariate analysis four factors had an adverse effect on TRM when using a VUD: low marrow cell dose (<3.65 x 10(8) TNC/kg, relative risk 2.05, CI 1.08-3.90, P = 0.029), late disease phase (relative risk 1.68, CI 1.03-2.74, P = 0.038), patient CMV seropositivity (relative risk 1.98, CI 1.25-3.13, P = 0.004) and high frequency of CTLP (relative risk 1.93, CI 1.18-3.13, P = 0.008). For HLA-identical sibling donor transplants the only factor that adversely impacted on TRM was late disease phase (P = 0.0004 in univariate analysis). CONCLUSION: High infused cell dose is a new modifiable factor associated with reduced TRM following allogeneic SCT using an unrelated donor for the treatment of CML. The data support the recommendation that bone marrow harvest teams should aim to collect the highest possible number of nucleated cells for recipients of unrelated donor transplants.

Adult↗