ABSTRACT
The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential (Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative (MAC) and reduced intensity conditioning (RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC (n = 158), Seq (n = 105), and MAC (n = 40). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years (IQR 53.5-65.6). For the entire cohort, 3 y overall survival (OS) was 50% (95% CI 45-56%) and relapse free survival (RFS) 45% (95% CI 40-51%). No significant differences in OS (log-rank p = 0.13) and RFS (log-rank p = 0.18) were observed between conditioning protocols. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and ≥20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Humans , Middle Aged , Aged , Retrospective Studies , Transplantation, Homologous/methods , Neoplasm Recurrence, Local , Myelodysplastic Syndromes/therapy , Chronic Disease , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Graft vs Host Disease/etiologyABSTRACT
Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09-6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.
Subject(s)
Cardiovascular Diseases , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Metabolic Syndrome , Adult , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Cross-Sectional Studies , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Metabolic Syndrome/etiology , Transplantation, Homologous/adverse effectsABSTRACT
Systemic anaplastic large cell lymphoma (sALCL) is a rare histological entity expressing the CD30 antigen that comprises around 11% of peripheral T-cell lymphoma. We analysed the outcome of patients with relapsed/refractory sALCL treated with autologous stem cell transplantation (auto-HCT). We included 65 adult patients (42 males; median age, 44 years); 24 patients had an ALK-ve sALCL. Fifty-one patients had chemosensitive disease at the time of transplant. Ten patients (15%) were treated with brentuximab vedotin (BV) before auto-HCT (median number of doses: 5). The median follow-up for surviving patients was 35 months (3-71). Three-year cumulative incidence of nonrelapse mortality and of relapse were 1.7% and 34%, respectively. Three-year progression-free survival and overall survival were 64% and 73%, respectively. No prognostic factors for any of the outcomes analysed were found in univariate analysis. There were no significant differences in any of the outcomes between patients who had received BV and the remainder. This is the largest analysis presented so far analysing the role of auto-HCT in patients with relapsed/refractory sALCL, showing a promising PFS and OS in this high-risk population. The potential impact of the administration of BV as salvage strategy before the procedure needs to be further elucidated.
Subject(s)
Hematopoietic Stem Cell Transplantation , Immunoconjugates , Lymphoma, Large-Cell, Anaplastic , Adult , Humans , Lymphoma, Large-Cell, Anaplastic/therapy , Male , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation, AutologousABSTRACT
BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Hodgkin Disease/drug therapy , Adolescent , Adult , Aged , Antineoplastic Agents/therapeutic use , Brentuximab Vedotin , Disease-Free Survival , Female , Hodgkin Disease/therapy , Humans , Immunoconjugates/therapeutic use , Male , Middle Aged , Nivolumab , Retrospective Studies , Stem Cell Transplantation , Young AdultABSTRACT
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
Subject(s)
Cardiovascular Diseases , Hematopoietic Stem Cell Transplantation/adverse effects , Metabolic Syndrome , Allografts , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Humans , Metabolic Syndrome/etiology , Metabolic Syndrome/prevention & control , Practice Guidelines as TopicABSTRACT
Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Hepatic Veno-Occlusive Disease/diagnosis , Adult , Biomarkers , Early Diagnosis , Hepatic Veno-Occlusive Disease/etiology , Hepatic Veno-Occlusive Disease/therapy , Humans , Risk Factors , Sensitivity and Specificity , Severity of Illness IndexABSTRACT
Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.
Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Postoperative Complications , Vascular Diseases , Adult , Biomarkers/blood , Humans , Postoperative Complications/blood , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Postoperative Complications/therapy , Risk Factors , Vascular Diseases/blood , Vascular Diseases/diagnosis , Vascular Diseases/etiology , Vascular Diseases/physiopathology , Vascular Diseases/therapyABSTRACT
The aim of this analysis was to explore the diversity of reduced intensity conditioning (RIC) in paediatric allo-SCT in daily practice across Europe. Data from the European Group for Blood and Marrow Transplantation (EBMT) Promise database from 1994 to 2008 were supplemented by a survey of EBMT centres performing paediatric allo-SCT on the current policy asking for the underlying diseases and for the drug combinations. Records from 161 centres from 30 countries were analysed and 139 various RIC regimens were reported. More centres applied RIC for malignant rather than for non-malignant diseases. In general, fludarabine (FLU)-based regimens predominated except for BU-based regimens in myeloid malignancies and haemoglobinopathies. Treosulfan (TREO) was mainly applied for unspecified malignant diseases and for haemophagocytic diseases. FLU-based regimens revealed the greatest number of different combinations. Correlating the number of regimens with the number of treating centres revealed the lowest variety in FLU and the highest variety in TBI and TREO. FLU/melphalane and FLU/CY were the most frequent combinations. This extreme heterogeneity in RIC may influence both the efficacy and the safety of the procedures, which requires further investigation. Optimization and standardization of RIC is the final goal to provide a platform for future prospective studies.
Subject(s)
Databases, Factual , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation , Quality of Life , Transplantation Conditioning/methods , Adolescent , Allografts , Antineoplastic Agents, Alkylating/administration & dosage , Busulfan/administration & dosage , Busulfan/analogs & derivatives , Child , Child, Preschool , Female , Humans , Infant , Male , Myeloablative Agonists/administration & dosage , Quality of Health Care , Retrospective Studies , Vidarabine/administration & dosage , Vidarabine/analogs & derivativesABSTRACT
OBJECTIVES: Evaluation of the periodontal status is necessary prior to management with high-dose chemotherapy before hematopoietic stem cell therapy (HSCT). During medical therapy, pre-existing periodontal conditions may exacerbate and cause local and systemic complications. When possible, maximal oral health should be achieved prior to engraftment. In this study, we aimed to determine the alterations occurred in the periodontal status of the patients after periodontal treatment and allogenic HSCT and evaluate the effect of intensive periodontal approach on the short-term complications of HSCT. METHODS: The alterations occurred in the periodontal tissues 3-4 weeks after periodontal treatment and after HSCT periods of 3 months for 29 patients treated with full-mouth periodontal treatment completed in 24 h in addition to eradication of dental foci, and oral hygiene status were evaluated using pocket depth measurements, presence of bleeding on probing and plaque and gingival indices. The incidence and severity of acute graft-versus-host disease (GVHD) and oral mucositis (OM) were recorded. Duration of engraftment period and the episode of febrile neutropenia were also evaluated. RESULTS: There were significant improvements in periodontal status after periodontal treatment (P<0.001). There were 14 (48.3%) patients without acute GVHD and 17 (58.6%) patients with no sign of OM. The majority of OM was at grade II level. There was a negative relation that exists between the percentage of BOP (+) sites and presence of OM (r=-0.518, P<0.05). CONCLUSIONS: Together with a significant reduction in gingival inflammation and maintenance of the improvement in periodontal health, remarkable decrease in the incidence and severity of OM were observed.
Subject(s)
Hematopoietic Stem Cell Transplantation , Myeloablative Agonists/therapeutic use , Periodontal Diseases/therapy , Periodontal Index , Postoperative Complications , Transplantation Conditioning/methods , Adult , Dental Plaque Index , Dental Prophylaxis , Female , Follow-Up Studies , Gingival Hemorrhage/classification , Graft vs Host Disease/etiology , Humans , Leukemia, Myeloid, Acute/surgery , Male , Middle Aged , Neutropenia/etiology , Oral Hygiene Index , Periodontal Debridement , Periodontal Pocket/classification , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Stomatitis/etiology , Tooth Extraction , Transplantation, Homologous , Young AdultABSTRACT
BACKGROUND: Well-recognized videocapillaroscopic patterns have been described in systemic sclerosis (SS). However, no studies have described the capillary abnormalities of sclerodermoid chronic graft-versus-host disease (Scl GVHD) developed after allogeneic haematopoietic stem cell transplantation (allo-HSCT). OBJECTIVES: The aims of this study were to find the characteristics of nailfold capillary changes in Scl GVHD after allo-HSCT. PATIENTS AND METHODS: Eighteen patients affected by Scl GVHD and a control group of 15 patients with lichenoid GVHD were evaluated. Duration and type of sclerodermoid GVHD, Raynaud phenomenon (RP), dysphagia, joint contractures, antinuclear antibodies (ANA), anti-Scl-70 and anticentromere (ACA) antibodies were investigated parameters. A nailfold capillary examination using a standard dermatoscope was performed on all fingers of each subject. RESULTS: Twelve patients were male and six were female with a mean age of 37 +/- 11.6 years. Joint retractions and dysphagia developed in 27.8% and 38.9% of the patients, respectively. Three (16.7%) patients had RP. Autoimmune markers like anti-Scl-70 and ACA were negative in all. Capillaroscopy was abnormal in 15 patients with Scl GVHD. A regular disposition of the capillary loops along with avascular whitish linear areas at the level of the last row, neovascularization with reticular pattern, capillary disorganization, haemorrhages, enlarged capillaries and avascular areas were the main features. No capillary abnormalities were observed in patients with lichenoid GVHD. There was no statistically significant correlation between ANA positivity, RP, joint retractions, dysphagia, extensiveness of Scl GVHD, duration of sclerodermoid lesions and nailfold capillaroscopy analysis. CONCLUSIONS: This study shows the identification of distinct nailfold capillaroscopy patterns in patients with Scl GVHD but it does not confer special risk for any other specific clinical symptoms of the disease.
Subject(s)
Graft vs Host Disease/pathology , Nails/blood supply , Scleroderma, Systemic/pathology , Adult , Capillaries/pathology , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Microscopic Angioscopy/methods , Middle Aged , Neovascularization, Pathologic/etiology , Neovascularization, Pathologic/pathology , Scleroderma, Systemic/etiology , Young AdultABSTRACT
The optimal timing for recombinant human (rh)G-CSF administration after chemotherapy for PBSC mobilization has not yet been determined. In this study, we compared two different time schedules of rhG-CSF; 4th (early) vs 7th day (late), in 48 consecutive patients with multiple myeloma and lymphoma undergoing PBSC mobilization with CE (CY 4 g/m(2) on day 1 and etoposide 200 mg/m(2) on days 1-3). The rhG-CSF dose was 10 microg/kg/day for all patients. Both groups were comparable in terms of sex, age and number of previously given different chemotherapy regimens. Duration of neutropenia, CD34(+) cell count on the first day of apheresis and numbers of aphereses were not statistically different between the two arms. However, the number of doses of rhG-CSF up to the first cycle of apheresis procedures was significantly lower in the late group than in the early group (P=0.005). The median number of total CD34(+) cells collected was 10.54 x 10(6)/kg (range 0.11-37.27) in the early group and 10.81 x 10(6)/kg (range 0.17-49.83) in the late group of rhG-CSF (P=0.781). We conclude that PBSC mobilization after late use of rhG-CSF is an effective approach and therefore, in routine clinical practice, late rhG-CSF may be used for PBSC collections after chemotherapy-based mobilization regimens in this cost-conscious era.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Mobilization/methods , Adult , Antigens, CD34 , Female , Humans , Leukapheresis/methods , Lymphoma, Non-Hodgkin/blood , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/therapy , Neutropenia/blood , Neutropenia/chemically induced , Peripheral Blood Stem Cell Transplantation , Recombinant Proteins , Time Factors , Transplantation, AutologousABSTRACT
SCT is a curative approach using chemo-, radio- and immunotherapy for malignant and non-malignant hematological disorders. The European Group for Blood and Marrow Transplantation (EBMT) has been collecting yearly data on a survey basis since 1990. The variables within the survey are limited to detailed indications, number of patients, transplant type, stem cell source, type of conditioning regimen and donor type. The transplant rates in certain indications, patterns of stem cell source selection and donor availability and alternative donor use were analyzed in detail. The Turkish transplant registry data within EBMT-European Activity Survey (EBMT-EAS) were delivered by the EBMT Activity Survey Office. We compared the national data with the international EBMT-EAS data pool.
Subject(s)
Hematopoietic Stem Cell Transplantation/statistics & numerical data , Registries , Humans , Transplantation, Homologous , TurkeySubject(s)
Graft Survival/genetics , Graft vs Host Disease/genetics , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation , Immunosuppressive Agents/administration & dosage , Methotrexate/administration & dosage , Methylenetetrahydrofolate Dehydrogenase (NAD+)/genetics , Polymorphism, Single Nucleotide , Acute Disease , Adolescent , Adult , Chronic Disease , Female , Graft vs Host Disease/enzymology , Humans , Leukemia/enzymology , Leukemia/genetics , Leukemia/therapy , Male , Middle Aged , Time Factors , Transplantation, Homologous , Young AdultABSTRACT
The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.
Subject(s)
Gastrointestinal Tract/pathology , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation , Hepatocytes/pathology , Transplantation Chimera , Adolescent , Adult , Chromosomes, Human, Y , Epithelium/injuries , Epithelium/pathology , Female , Gastrointestinal Tract/injuries , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Severity of Illness IndexABSTRACT
The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/therapy , Lymphoma/therapy , Stem Cell Transplantation/methods , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Combined Modality Therapy , Female , Humans , Lymphoma/mortality , Lymphoma, Non-Hodgkin/mortality , Male , Melphalan/administration & dosage , Middle Aged , Retrospective Studies , Stem Cell Transplantation/adverse effects , Survival Analysis , Thiotepa/administration & dosage , Transplantation, Autologous , Treatment OutcomeABSTRACT
The aim of this study was to study the usefulness of erythrocyte antigen (EA) measurement to study engraftment after allogeneic HSCT. In all, 31 consecutive patients receiving HLA-identical bone marrow (BM) (n=13) or peripheral blood stem cells (n=18) were investigated. Apart from the ABO group, 15 EAs representing six minor blood groups were followed by the simple tube agglutination technique. A total of 20 (64.5%) patients received ABO-identical, eight (25.8%) received ABO minor and three (9.7%) received ABO major mismatched grafts. In all, 29 patients were followed for a median of 12 (6-16) months; 65% of the patients expressed donor type EA 1 month and almost all did so 6 months after transplant. Reticulocyte engraftment was significantly shorter than EA engraftment (median 18 vs 35 days) (P=0.001). Patients who received PB stem cells showed significantly faster EA and reticulocyte engraftment than patients who received BM stem cells (P=0.038 and 0.025). ABO compatibility did not have an impact on reticulocyte and EA engraftment (P=0.4 and 0.55). The earliest donor type EA detected was from the Rh and Kidd system. These data suggest that EA and reticulocyte assays are useful in monitoring engraftment.
Subject(s)
Antigens/blood , Reticulocytes/transplantation , Stem Cell Transplantation/methods , Adolescent , Adult , Anemia, Aplastic/therapy , Antigens/therapeutic use , Blood Grouping and Crossmatching , Carcinoma, Renal Cell/therapy , Erythrocytes/immunology , Female , Humans , Kidney Neoplasms/therapy , Leukemia/therapy , Male , Middle Aged , Reticulocyte Count , Treatment OutcomeABSTRACT
Although hepatitis B virus (HBV) reactivation in HBV carriers undergoing immunosuppressive therapy is clearly documented, the role of antiviral prophylaxis in such individuals is still controversial. The aim of this study was to determine the efficacy of lamivudine prophylaxis in HBV carriers with haemato/oncological malignancies, who receive chemotherapy. Eighteen HBV carriers with malignancy, who were candidates for chemotherapy, were enrolled. Eight subjects (three with leukaemia, four with lymphoma and one with multiple myeloma) were enrolled for prophylactic lamivudine therapy. The remaining 10 patients (six with leukaemia, three with lymphoma and one with breast cancer) were not treated with lamivudine and were used as a control. Lamivudine was administered beginning on the same day as the chemotherapy and was maintained for a year after chemotherapy was discontinued. No HBV-related mortality was observed in either group. In the lamivudine-treated group, none of the subjects had clinical, biochemical or serological evidence of HBV reactivation during the time they were receiving chemotherapy and after their chemotherapy was discontinued. In contrast, five of the 10 HBV carriers not receiving lamivudine therapy experienced a reactivation of HBV infection. This reactivation of HBV was observed during the chemotherapy in four with one individual experiencing a HBV activation 12 months after chemotherapy was discontinued. No lamivudine-related major adverse effects were observed. Hence prophylactic lamivudine treatment in HBV carriers with haemato/oncological malignancy receiving chemotherapy prevents chemotherapy-induced HBV reactivation.
Subject(s)
Carrier State/virology , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Hepatitis B/prevention & control , Lamivudine/therapeutic use , Adult , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antiviral Agents/therapeutic use , DNA, Viral/blood , Female , Hepatitis B Antibodies/blood , Hepatitis B Antigens/blood , Hepatitis B virus/isolation & purification , Humans , Lamivudine/administration & dosage , Male , Middle AgedABSTRACT
The hypercoagulable state caused by the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been cited in anecdotal reports. Since tissue factor (TF) is the main initiator of the coagulation cascade, we examined if rhG-CSF had an inductive effect on the TF-dependent pathway in 18 healthy donors receiving rhG-CSF (10 microg/kg/day x 5 days) for peripheral blood progenitor cell mobilization. After rhG-CSF, there were increases both in TF antigen (TF:Ag) (P=0.01) and TF procoagulant activity (TF:PCA) (P=0.06) plasma levels and in TF:Ag cytofluorimetric expression on CD33 (+) cells (P=0.04). Mean activities of FVIII and vWF also increased significantly. Thrombin time was slightly prolonged (P=0.06) due to significant increases in plasma D-dimer levels. In addition, while FIX activity remained stable, there were marked reductions in mean plasma FX and FII activities and a slight decrease in FVII activity that resulted in a significant prolongation of prothrombin time within normal ranges. In conclusion, the administration of rhG-CSF led to a "prothrombotic state" via stimulation of TF and increased endothelial markers, such as F VIII and vWF. In the light of these findings, the use of rhG-CSF for stem cell mobilization should be undertaken cautiously in healthy donors with underlying thrombotic risk factors.
Subject(s)
Blood Coagulation Disorders/chemically induced , Blood Coagulation/drug effects , Granulocyte Colony-Stimulating Factor/adverse effects , Hematopoietic Stem Cell Transplantation , Thromboplastin/metabolism , Adult , Factor IX/metabolism , Factor VII/metabolism , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Male , Middle Aged , Prothrombin/metabolism , Recombinant Proteins , Thrombin Time , Tissue DonorsABSTRACT
This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.