Biomedical subjects

R Szydlo

Publications and source records attributed to R Szydlo.

At least 19 recordsLinked to original sources

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

Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors.

Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77+/-5% for the MSD and 67+/-11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.

Adolescent↗

PubMed2005

Monitoring patients in complete cytogenetic remission after treatment of CML in chronic phase with imatinib: patterns of residual leukaemia and prognostic factors for cytogenetic relapse.

We monitored BCR-ABL transcript levels by quantitative real-time PCR in 103 patients treated with imatinib for chronic myeloid leukaemia in chronic phase for a median of 30.3 months (range 5.5-49.9) after they achieved complete cytogenetic remission (CCyR). The patients could be divided into three groups: (1) in 32 patients transcript levels continued to decline during the period of observation (nadir BCR-ABL/ABL ratio 0.015%); in five of these patients BCR-ABL transcripts became undetectable on repeated testing, (2) in 42 patients the transcript levels reached a plateau and (3) in 26 patients transcript numbers increased and the initial CCyR was lost. Three patients were not evaluable. Patients who remained in CCyR for at least 24 months appeared to have a low risk of subsequent cytogenetic relapse. We conclude that the pattern of 'residual' disease after achieving CCyR on imatinib is variable: some patients in CCyR show a progressive reduction in the level of residual disease, some reach a plateau where transcript numbers are relatively stable and others relapse with Ph-positive metaphases.

Adolescent↗

PubMed2005

The combination of intermediate doses of thalidomide with dexamethasone is an effective treatment for patients with refractory/relapsed multiple myeloma and normalizes abnormal bone remodeling, through the reduction of sRANKL/osteoprotegerin ratio.

The aim of this study was the evaluation of the effect of intermediate doses of thalidomide with dexamethasone (Thal/Dex) on disease course and bone disease in patients with refractory/relapsed myeloma who were under zoledronic acid therapy. We studied 35 patients, who received thalidomide at a dose of 200 mg/daily. We measured, pre-, 3 and 6 months post-treatment soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), osteoprotegerin (OPG), osteopontin (OPN), markers of bone resorption and formation. Before treatment, patients had increased levels of sRANKL/OPG ratio, bone resorption markers and OPN, while they had suppressed bone formation. The pretreatment sRANKL/OPG ratio correlated with the extent of bone disease. Thal/Dex administration resulted in a significant reduction of sRANKL/OPG ratio, and bone resorption. Bone formation, OPG and OPN did not show any alteration. Changes of sRANKL/OPG ratio correlated with changes of bone resorption markers. Thal/Dex was given for a median time of 10 months and the median follow-up period was 22 months. The response rate was 65.7%. The median survival was 19.5 months. beta2-microglobulin, type of response and International Staging System predicted for survival. These results suggest that the combination of intermediate dose of Thal/Dex is effective in patients with refractory/relapsed myeloma and improves abnormal bone remodeling through the reduction of sRANKL/OPG ratio.

Adult↗

PubMed2005

The use of LYVE-1 antibody for detecting lymphatic involvement in patients with malignant melanoma of known sentinel node status.

BACKGROUND: Sentinel node (SN) status is the most important prognostic indicator in patients with cutaneous melanoma without clinically evident metastatic spread, but the procedure is associated with considerable morbidity. The LYVE-1 lymphatic marker offers the possibility of studying lymphangiogenesis and tumour metastasis within the primary excision. AIMS: To establish whether lymphatic vessel numbers/distribution within the primary tumour correlated with SN status. To assess whether tumour cells were easily demonstrable within lymphatics and could be used as a surrogate for SN status. METHODS: Double immunostaining for LYVE-1 and S100 in cutaneous biopsies from 18 SN+ patients with no lymphatic/vascular involvement on routine histology and 18 SN- patients matched for tumour thickness and ulceration. RESULTS: Lymphatic vessels were detected in all cases. Vessels within the tumour mass were suggestive of active lymphangiogenesis; those outside were mainly mature vessels with well defined walls. Tumour cells within lymphatics were detected in one of 18 SN- and five of 18 SN+ patients. Lymphatics containing tumour cells were all outside the tumour mass in well formed vessels, suggesting melanoma cell invasion into preformed lymphatics. There was no significant difference in lymphatic counts between SN+ and SN- patients. Although peritumorous lymphatic counts were higher in ulcerated than non-ulcerated melanomas, they did not vary with Breslow thickness. CONCLUSION: LYVE-1 staining can reliably demonstrate lymphatic vessel distribution, but lymphatic counts cannot predict melanoma metastatic potential and cannot substitute for SN biopsy. LYVE-1 immunostaining can detect melanoma cells within lymphatics, but is unreliable in predicting melanoma metastasis, failing to detect metastatic spread in more than two thirds of patients with regional node metastasis.

Biomarkers, Tumor↗

PubMed2004

Treatment for primary refractory Hodgkin's disease: a comparison of high-dose chemotherapy followed by ASCT with conventional therapy.

Our previously published study showed promising results of autologous stem cell transplantation (ASCT) in patients with primary resistant Hodgkin's disease (HD). Probabilities of overall survival (OS) and progression-free survival (PFS) at 3 years were 55 and 36%, respectively. The present study was undertaken to compare these results with conventionally treated patients and thus evaluate therapeutic options. Retrospective data on 76 adult patients who underwent ASCT were matched with 76 conventionally treated patients from 17 centers. Comparison of clinical characteristics in both groups showed that ASCT patients were younger (24 vs 31.5 years, P=0.001), more frequently presented with 'B' symptoms (P=0.03) and that more patients treated with chemotherapy (CT) had elevated LDH (P=0.03). In univariate analyses, bulky disease (P=0.0043) and complete resistance to standard CT (P=0.051) were found to be risk factors for OS. In a multivariate survival analysis only bulky disease was found to an independent prognostic factor (P=0.005). There was no difference in survival between the treatment groups with 5 years OS 33.7 (CI: 23-46) in the ASCT group and 35.6% (CI: 25-50) for the CT group (P=0.92). We conclude that ASCT is not superior to standard CT for treatment of patients with primary refractory HD.

Adolescent↗

PubMed2004

Autologous stem cell transplantation normalizes abnormal bone remodeling and sRANKL/osteoprotegerin ratio in patients with multiple myeloma.

The osteoprotegerin (OPG)/receptor activator of NF-kappa B ligand (RANKL) system has a major role in the pathogenesis of bone disease in myeloma (MM). The effect of autologous stem cell transplantation (ASCT) on bone turnover in MM was evaluated in 51 patients (35M/16F). Markers of bone resorption (NTX, TRACP-5b), bone formation (bone-alkaline phosphatase (bALP), osteocalcin), OPG and sRANKL were measured pre- and every month post-ASCT. The median follow-up period was 12 months. Four patients were transplanted in CR, 44 were transplanted in PR and three patients had progressive/resistant disease. All patients received bisphosphonates both pre- and post-ASCT. At baseline the majority of patients had increased NTX, TRACP-5b levels, and sRANKL/OPG ratio, while markers of bone formation were strongly suppressed. ASCT produced a significant reduction of sRANKL/OPG ratio, with a concomitant decrease of NTX, and TRACP-5b levels, starting the second month post-ASCT. Bone formation markers, osteocalcin and bALP, started to increase after the 9th and 11th month post-ASCT, respectively, while the increase of OPG preceded this. These results provide biochemical evidence that ASCT normalizes the abnormal bone resorption in MM patients possibly through the decrease of RANKL/OPG ratio, while bone formation requires a longer period to return to normal.

Adult↗

PubMed2004

The use of a national transplant registry to benchmark transplant outcome for patients undergoing autologous and allogeneic stem cell transplantation in the United Kingdom and Ireland.

As part of its clinical governance programme the British Society for Blood and Marrow Transplantation (BSBMT) undertook an analysis of transplant outcome for adults undergoing human leucocyte antigen - identical sibling allogeneic transplantation for chronic myeloid leukaemia (CML) in first chronic phase (CP1) or autologous transplantation for Hodgkin's disease (HD). The study aimed to compare transplant-related mortality (TRM) and survival for patients reported to the BSBMT with patients transplanted in the rest of Europe, reported to the European Group for Blood and Marrow Transplantation (EBMT). The outcomes for 104 allogeneic transplants for CML in 24 UK/Irish centres were compared with 775 allografts in 145 other European centres. For HD, 241 autografts from 38 UK/Irish centres were compared with 1145 transplants in 239 other European centres. For both diseases, the cohorts were broadly matched with the exception of CML, where 85% of patients were transplanted <1 year from diagnosis in the UK/Ireland compared with 68% in the EBMT (P = 0.001). Cox regression analysis was undertaken using known delineated variables affecting transplant outcome in addition to the registry of origin. The adjusted survival curves for CML showed no significant differences between the two groups, with 3-year survival probabilities of 70.2% and 67.1% for the EBMT and BSBMT cohorts respectively. Likewise, the analysis for HD showed overlapping survival curves, with 3-year survival probabilities of 71.8% (EBMT) and 70.8% (BSBMT). TRM was not statistically different in either disease. This study demonstrates the potential for using national registries to benchmark transplant outcome against the EBMT registry.

Adolescent↗

PubMed2001

Early detection of BCR-ABL transcripts by quantitative reverse transcriptase-polymerase chain reaction predicts outcome after allogeneic stem cell transplantation for chronic myeloid leukemia.

The reverse transcriptase-polymerase chain reaction (RT-PCR) has become widely used for monitoring minimal residual disease after allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML). However, most of these studies were performed using qualitative RT-PCR, and the interpretation of the results obtained has been conflicting. The correlation of a quantitative RT-PCR test performed early after SCT (at 3 to 5 months) and long-term outcome of CML patients surviving for more than 6 months was studied. Between January 1991 and June 1999, data from 138 CML patients who received allografts were evaluated. Early RT-PCR results were classified as (1) negative if there were no BCR-ABL transcripts detected (n = 61), (2) positive at low level if the total number of BCR-ABL transcripts was less than 100 per microg RNA and/or the BCR-ABL/ABL ratio was less than 0.02% (n = 14), or (3) positive at high level if transcript levels exceeded the thresholds defined above (n = 63). Three years after SCT the cumulative incidence of relapse was 16.7%, 42.9%, and 86.4%, respectively (P =.0001). The relationship between BCR-ABL transcript level and probability of relapse was apparent whether patients had received sibling or unrelated donor SCT and also whether or not the transplantation was T cell depleted. The results suggest that quantitative RT-PCR performed early after SCT is useful for predicting outcome and may help to define the need for further treatment.

Actuarial Analysis↗

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↗

PubMed2000

Effect of short-term interferon therapy on the outcome of subsequent HLA-identical sibling bone marrow transplantation for chronic myelogenous leukemia: an analysis from the international bone marrow transplant registry.

Allogeneic bone marrow transplantation (BMT) is the only curative therapy for chronic myelogenous leukemia (CML), though several studies indicate that prolonged survival can result from interferon-alpha (IFN-alpha) treatment. IFN-alpha is now often used as initial therapy for CML, before donor availability is known. Because identifying potential donors can take several weeks to months, it is important to know whether IFN-alpha adversely affects outcome of a subsequent BMT. If it does, initiation of IFN-alpha therapy might be delayed until donor availability is determined and avoided in patients for whom BMT is planned. We studied 873 patients who received HLA-identical sibling BMT for chronic-phase CML in 153 centers participating in the International Bone Marrow Transplant Registry. The object was to compare outcome in the 664 who received only hydroxyurea before BMT with outcome in the 209 who received IFN-alpha with or without hydroxyurea. The median duration of IFN-alpha therapy was 2 months (range, 1 to 39 months). Cox proportional hazards analysis was used to compare engraftment, graft-versus-host disease (GVHD), nonrelapse mortality, relapse, survival, and leukemia-free survival after adjustment for other prognostic variables. We found a higher risk of nonengraftment among patients given IFN-alpha than among those given hydroxyurea alone (2% versus 0.2%; P = 0.01). Patients who received IFN-alpha had a lower risk of relapse (relative risk, 0.17; 95% confidence interval, 0.04-0.70). Probabilities of GVHD, nonrelapse mortality, survival, and leukemia-free survival were similar in the two treatment groups. These results suggest that a short course of IFN-alpha does not adversely affect survival after a subsequent HLA-identical sibling BMT for chronic-phase CML. (Blood. 2000;95:410-415)

Actuarial Analysis↗

PubMed2000

High-dose busulphan alone as cytoreduction before allogeneic or autologous stem cell transplantation for chronic myeloid leukaemia: a single-centre experience.

Transplant-related morbidity and mortality remain a major problem following stem cell transplantation (SCT). The use of high-dose single-agent busulphan before allogeneic or autologous SCT may be a reasonable compromise between maintaining cytoreductive efficacy and minimizing toxicity in patients with chronic myeloid leukaemia (CML). Seventy patients with CML have received busulphan as the only cytoreductive therapy before SCT on 79 occasions. The probability of survival of the 14 allogeneic recipients (all of whom were undergoing a second transplant from the original donor) was 78% at 5 years. Sixty-five autologous SCT were performed in 56 patients, of whom 40 were in late chronic phase. The actuarial 3-year post-autograft survival was 54% for these 56 first autografts. For patients in chronic phase, the 3-year survival was 76% compared with 30% at 2 years for those with advanced phase disease. Busulphan therapy was well tolerated, and except for mild mucositis little toxicity was experienced. None of these patients developed hepatic veno-occlusive disease (VOD). Nine patients (one allogeneic and eight autologous recipients) received several doses of an intravenous formulation of busulphan with very low toxicity. High-dose busulphan alone appears sufficient to provide adequate cytoreduction and immunosuppression in second allogeneic transplants and is also effective as cytoreduction before autologous SCT in patients with CML.

Adolescent↗

PubMed2000

Non-random involvement of chromosome 13 in patients with persistent or relapsed disease after bone-marrow transplantation for chronic myeloid leukemia.

Chronic myeloid leukemia (CML) patients with persistent or relapsed disease following bone-marrow transplantation (BMT) usually show both clonal and non-clonal cytogenetic changes in addition to the Philadelphia (Ph) translocation. These changes are presumably due to conditioning prior to transplantation and are generally not thought to be of clinical significance. We have examined the additional cytogenetic changes found in Ph+ve cells after BMT in 47 CML patients. Forty patients showed clonal changes. The involvement of each chromosome was compared statistically with expected values assuming that further chromosome changes are random and related to chromosome size. In clones that comprised 50% or more of the Ph+ve metaphases, chromosome 13 was involved in 12 of 22 clones (55%); this was highly significant when compared with the theoretical expected value of 3.2 (14.5%) (P < 0.001). The chromosome 13 rearrangements comprised both translocations and deletions. By means of FISH with a panel of 13q YAC clones, the breakpoints in 6 of these patients were investigated, but no common site of translocation was identified. The YAC panel was then used on material from 6 patients with chromosomal deletions. A common region of deletion was identified at 13q12-14, suggesting the presence of one or more tumor suppressor genes. We conclude that chromosome 13 deletions are non-randomly overrepresented in Ph+ve metaphases following BMT for CML. Genes Chromosomes Cancer 27:278-284, 2000.

Bone Marrow Transplantation↗

PubMed1999

A comparison of prophylactic vs pre-emptive ganciclovir to prevent cytomegalovirus disease after T-depleted volunteer unrelated donor bone marrow transplantation.

The prophylactic and pre-emptive use of ganciclovir (GCV) both reduce significantly the incidence of CMV disease after sibling BMT but it is unclear which of these strategies is best for volunteer unrelated donor (VUD) BMT patients. We reviewed 49 consecutive patients, who received a T-depleted VUD BMT (from March 1990 to March 1996) for the treatment of CML in chronic phase, and were CMV seropositive before transplant or had a CMV seropositive donor. Patients were conditioned with cyclophosphamide (120 mg/kg for 2 days) and total body irradiation (13.2-14.4 Gy). Prophylaxis for GVHD was cyclosporin A and methotrexate with ex vivo or in vivo T cell depletion. Twenty-seven patients received pre-emptive GCV if CMV infection was detected by short-term culture before day +120 post BMT. Twenty-two patients received prophylactic GCV from engraftment until day +120 post BMT. The probabilities of CMV infection and disease occurring by 1 year post-BMT were greater in the pre-emptive GCV group than in the prophylactic GCV group (73.8% and 64.0% vs 53.1% and 30.0%, respectively; P=0.04 and 0.07). The incidence of death from CMV disease was similar in both groups (3/12 (25%) vs 3/10 (30%), respectively) and there was no difference in 1 year survival (55.6% vs 54.2%, respectively). New strategies are urgently required for the prevention of CMV disease after T-depleted VUD BMT.

Adult↗

PubMed1999

Abnormal patterns of immunoglobulin heavy chain gene DNA fingerprinting during chronic phase chronic myeloid leukemia.

Using IgH DNA fingerprinting we have previously demonstrated clonal immunoglobulin heavy chain (IgH) gene rearrangements during chronic phase (CP) chronic myeloid leukemia (CML) in patients destined to develop lymphoid blast crisis (L-BC). In view of this we decided to follow a cohort of CP CML patients to determine the frequency with which abnormal IgH fingerprints are found and their relationship, if any, to treatment regimen. Thirty three, initially CP, CML patients were studied on 111 occasions over a 16 month period using consensus PCR amplification of the third complementarity determining region (CDR3) of the IgH gene and high resolution polyacrylamide gel electrophoresis (IgH DNA fingerprinting). Of these 33 patients, thirteen received interferon-alpha (IFN) containing regimens and 15 non-IFN containing regimens throughout the study period. Five patients received variable therapy. During the period of observation 7 patients experienced disease progression: 5 accelerated phase, I L-BC and I myeloid blast crisis (M-BC). Abnormal IgH fingerprints were seen in 29 of the 111 (26%) specimens analysed. The 28 patients who received uniform therapy (IFN or non-IFN) over the 16 months were classified as "normal" (n = 18, normal pattern on all occasions) or "abnormal" (n = 10, abnormal on 1 or more occasions). Analysis by patient group (normal vs abnormal) showed that fingerprint abnormalities were associated with an elevated peripheral blood lymphocyte count (p = 0.0001) but not with changes in the total white cell count. Comparison of the IFN vs. non-IFN groups showed the former all had normal patterns whereas 10 of 15 non-IFN therapy patients were abnormal (p = 0.00023). The peripheral blood lymphocyte counts in the normal vs abnormal patients within the non-IFN group were not significantly different. The patient who developed L-BC demonstrated a persistent IgH fingerprint pattern abnormality from 7 months prior to the diagnosis of L-BC. The M-BC patient had a normal pattern at all times. We conclude that: (1) abnormal IgH fingerprints are found in a significant number of CP CML patients; (2) in this cohort the use of IFN was associated with normal CP CML IgH fingerprints, and (3) detection of abnormal IgH fingerprints may be highly predictive for the lineage of impending blast crisis.

DNA Fingerprinting↗

PubMed1998

Interleukin 3 (IL-3), but not stem cell factor (SCF) increases self-renewal by human erythroid burst-forming units (BFU-E) in vitro.

Interleukin 3 (IL-3) and stem cell factor (SCF) are both important regulators of early haemopoietic cell development. Here, we have compared their effects or the kinetics of erythroid burst formation by BFU-E in normal adult bone marrow. We grew the BFU-E in the presence of erythropoietin (Epo) alone, Epo + IL-3 or Epo + SCF and scored the numbers of subcolonies in individual bursts after 14 days. The data were plotted as the cumulative distribution of the numbers of subcolonies per erythroid burst then linearised by logarithmic transformation. Analysis of the data revealed that IL-3 increases the numbers of subcolonies in BFU-E whilst SCF increases the size of the subcolonies themselves. Experiments involving combinations of Epo + IL-3 + SCF and the delayed addition of IL-3 or SCF indicated that the actions of IL-3 and SCF are largely independent of one another. We conclude that: (1) IL-3 acts at an earlier stage of erythroid differentiation than SCF, and (2) it may be possible to classify haemopoietic growth factors according to their effects on cell kinetics in vitro.

Cells, Cultured↗

PubMed1998

Adoptive immunotherapy for relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: equal efficacy of lymphocytes from sibling and matched unrelated donors.

Lymphocyte transfusion from the marrow donor (DLT) is well established as an effective therapy for relapse of CML post allogeneic BMT. Reports thus far have been mostly limited to patients who received DLT from a matched sibling donor. We compared the efficacy and toxicity of DLT in 30 patients who were treated with cells from their HLA-identical sibling (n = 18) or from their phenotypically HLA-matched unrelated marrow donor (n = 12). The overall probability of obtaining a cytogenetic remission was 69% (95%CI: 51-83%) and was not significantly different between the two groups. The disease stage at the time of DLT was the only factor associated with cytogenetic remission by multivariate analysis; patients treated in cytogenetic or molecular relapse (n = 11) were seven times more likely (RR = 7.4, 95%CI: 2.4-22.4, P = 0.0005) to respond compared to patients treated for hematologic relapse (n = 19). There was a trend towards more acute GVHD II-IV in the unrelated donor group (58 vs 39%, P = 0.09), but the probability of developing extensive chronic GVHD was not significantly different (56 vs 39%, P = 0.4). We conclude that transfusion of donor cells from HLA-matched volunteer donors does not appreciably increase the risk of GVHD compared with transfusion of cells from HLA-identical siblings in patients with CML who relapse following allogeneic BMT. Conversely, there is no evidence for an increased graft-versus-leukemia effect after DLT from volunteer donors.

Adult↗

PubMed1997

Factors influencing the outcome of bone marrow transplants using unrelated donors.

The use of unrelated donors for bone marrow transplantation (BMT) is associated with an increased morbidity and mortality when compared with HLA-identical donors, primarily due to an increased rate of graft-versus-host disease, but also to increased susceptibility to infections and graft failure. HLA matching for donors and recipients is the single most important factor influencing the outcome of BMT. However, unrelated donor selection generally relies on matching only for HLA-A, -B and -DR antigens without considering potential incompatibility for other HLA loci, such as HLA-C, -DQ and -DP. In addition, other factors that affect the outcome of BMT need to be taken into consideration in selecting the best unrelated donor. In this review, we will focus on the effects of HLA-associated factors in determining the result of a transplant procedure. We will also mention other relevant factors, drawing on our experience of laboratory studies performed at The Anthony Nolan Research Institute and clinical studies at the Hammersmith Hospital in London.

Bone Marrow Transplantation↗