Subject(s)
Allografts/physiopathology , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/physiology , Reoperation/methods , Adult , Aged , Antigens, CD34/analysis , Antigens, CD34/metabolism , Cohort Studies , Delayed Graft Function/physiopathology , Delayed Graft Function/therapy , Female , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cells/metabolism , Humans , Male , Middle Aged , Transplantation Conditioning/methods , Young AdultABSTRACT
Antifungal prophylaxis (AP) has dramatically changed the epidemiology of invasive aspergillosis (IA). To better understand the differences in terms of clinical significance of IA between allogeneic stem cell transplantation (allo-SCT) recipients and patients treated for leukemia, we report a single-center study of 735 unselected consecutive patients treated between 2000 and 2004, before the era of systematic AP. Probable or confirmed IA were observed in 29 patients (2008 EORTC/MSG criteria), including 7/235 undergoing allo-SCT (5.2%), 19/380 treated for acute leukemia (5.0%), 1/116 for chronic lymphocytic leukemia (0.9%) and 2/104 for myelodysplastic syndrome (1.9%). In allo-SCT recipients, IA occurred later than in leukemia patients, after the neutropenic period. The median time between the last treatment and the diagnosis of IA was 231 days (range, 68-341) in allo-SCT recipients and 17 days (6-57) in leukemia patients (P<0.001). Importantly, the 7 cases of IA after allo- SCT occurred only in patients treated with corticosteroids for graft-versus-host disease (GVHD). Mortality directly related to IA was 24%. The 100-day, 2-year and 10-year overall survival were 42.9%, 0%, 0% in allo-SCT recipients compared to 68.1%, 18.2%, 13.6% in leukemia patients, respectively (P≥0.05). These poor outcomes were mainly attributable to non-relapse mortality (NRM). In conclusion, our data allows distinguishing 2 types of IA occurring at different time in the treatment course. In both cases, the NRM is very high and treatment remains challenging. Thus, systematic broad-spectrum AP against Aspergillus should be considered in acute leukemia patients during the neutropenic phase and in all patients undergoing allo-SCT who develop GVHD.
ABSTRACT
Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.
Subject(s)
Cyclophosphamide/therapeutic use , Hodgkin Disease/therapy , Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Transplantation, Haploidentical , Adult , Cord Blood Stem Cell Transplantation , Disease-Free Survival , Female , Follow-Up Studies , Graft vs Host Disease , HLA Antigens , Histocompatibility , Hodgkin Disease/mortality , Humans , Male , Retrospective Studies , Stem Cell Transplantation/standards , Transplantation, Homologous , Unrelated Donors/supply & distributionABSTRACT
The monitoring of the minimal residual disease by Wilms' tumor 1 expression (MRDWT1) is a standardized test, which can be used in over 80% of patients with AML. To investigate the prognostic value of MRDWT1 in patients undergoing allogeneic stem cell transplantation (allo-SCT) for AML, MRDWT1 was monitored 3 months after transplantation in 139 patients. MRDWT1 positivity did not lead to any therapeutic intervention. Median follow-up was 39.3 (6.4-99.8) months. Patients with positive MRDWT1 at 3 months experienced more often post-transplant relapse (27/30, 90%) than those with negative MRDWT1 (16/109, 14.7%) (P<0.0001). Similarly, a shorter 3-year event-free survival (EFS) was observed in MRDWT1-positive patients (10% vs 72.3% in MRDWT1-negative patients, P<0.0001). The correlation between relapse and MRDWT1 was stronger in blood than in bone marrow samples. Multivariate analysis confirmed the detrimental role of 3-month positive MRDWT1 for relapse (hazard ratio (HR): 15.42; 95% confidence interval (CI): 7.53-31.59; P<0.0001) and EFS (HR: 10.71; 95% CI: 5.41-21.21; P<0.0001). Interestingly, 3-month chimerism was less predictive of relapse than positive MRDWT1. In conclusion, our results demonstrate the usefulness of peripheral blood MRDWT1 monitoring in identifying very high-risk patients, who could benefit from an early preemptive treatment, and those who do not need such an intervention.
Subject(s)
Hematopoietic Stem Cell Transplantation/mortality , Leukemia, Myeloid, Acute/therapy , Neoplasm, Residual/diagnosis , WT1 Proteins/analysis , Bone Marrow/chemistry , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Male , Prognosis , Recurrence , Transplantation, Homologous , Treatment Outcome , WT1 Proteins/blood , Wilms Tumor/chemistryABSTRACT
In an attempt to reduce the incidence of chronic GVHD (cGVHD) after reduced-intensity conditioning (RIC), we used BM instead of PBSC and added melphalan 100 mg/m(2) to the classical association of fludarabine, 30 mg/m(2)/day for 3 days and TBI, 200 cGy (FLUIM regimen). Between 2000 and 2012, 51 patients received BM with the FLUIM regimen (group A), and 124 received BM (n=22) or PBSC (n=102) with another RIC regimen (group B). Donors were siblings (n=123) or HLA-matched 10/10 unrelated (n=52). Full donor-type chimerism at day 100 was more often recorded in group A (86%) than in group B (62%); P<0.001. There was no difference between the two groups in terms of OS and EFS, acute GVHD, relapse and non-relapse mortality incidence. cGVHD occurred more often in group B (41%) than in group A (23%); P=0.021. In multivariate analysis, the two risk factors associated with the development of cGVHD were conditioning in group B (hazard ratio (HR)=2.871, 95% confidence interval (CI) (1.372-6.006); P=0.005) and CD34(+) count (HR=1.009, 95% CI (1.006-1.011); P<0.001). In conclusion, the FLUIM regimen followed by BM leads to more frequent full-donor chimerism and a reduced incidence of cGVHD without compromising relapse and survival.
Subject(s)
Bone Marrow Transplantation , Bone Marrow/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Stem Cell Transplantation , Transplantation Conditioning , Transplantation, Homologous , Adolescent , Adult , Aged , Female , Graft vs Host Disease , Humans , Male , Melphalan/administration & dosage , Middle Aged , Recurrence , Retrospective Studies , Treatment Outcome , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Young AdultABSTRACT
Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.
Subject(s)
Autoimmune Diseases/surgery , Stem Cell Transplantation/methods , Transplantation, Autologous/methods , France , Humans , Immunosuppressive Agents , Postoperative Care , Stem Cell Transplantation/adverse effects , Stem Cell Transplantation/standards , Transplantation, Autologous/adverse effects , Transplantation, Autologous/standardsABSTRACT
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here, we report our recommendations regarding the use of donor lymphocyte injection (DLI) in the prophylactic, pre-emptive and curative settings. This work has been limited to allogeneic stem cell transplantations from an HLA-matched (10/10) or -one antigen-mismatched (9/10) donor.
Subject(s)
Lymphocyte Transfusion , Stem Cell Transplantation/standards , Transplantation, Homologous/standards , Haplotypes , Histocompatibility Testing , Humans , Recurrence , Stem Cell Transplantation/methods , Tissue and Organ Procurement , Transplantation, Homologous/methodsABSTRACT
Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part one of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.
Subject(s)
Haplotypes , Histocompatibility Testing , Stem Cell Transplantation/standards , Tissue Donors , Transplantation, Homologous/standards , Adult , Aged , Animals , Bone Marrow Transplantation , Cyclophosphamide , Donor Selection , France , Humans , Immunosuppressive Agents , Middle Aged , Stem Cell Transplantation/methods , Transplantation Conditioning , Transplantation, Homologous/methodsABSTRACT
Haploidentical allogeneic stem cell transplantation (CST) has globally taken off in the past decade. It appears to be a valid alternative to other sources of stem cells; however, further research is necessary to validate the use of this approach in standard patient care. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. This is part two of the recommendations regarding allogeneic stem cell transplantation from an HLA-haploidentical related donor.
Subject(s)
Haplotypes , Histocompatibility Testing , Stem Cell Transplantation/standards , Tissue Donors , Transplantation, Homologous/standards , Bone Marrow Transplantation , Donor Selection , France , Humans , Immunosuppressive Agents , Stem Cell Transplantation/methods , Transplantation Conditioning , Transplantation, Homologous/methodsABSTRACT
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of virus respiratory syncytial virus (RSV), human herpes virus 6 (HHV6) or adenovirus allogeneic Stem Cell Transplantation.
Subject(s)
Adenoviridae Infections/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Respiratory Syncytial Virus Infections/therapy , Roseolovirus Infections/therapy , Virus Activation/physiology , Adenoviridae/physiology , Adenoviridae Infections/epidemiology , Adenoviridae Infections/etiology , Consensus , Donor Selection/standards , Hematopoietic Stem Cell Transplantation/standards , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Herpesvirus 6, Human/physiology , Humans , Immunosuppression Therapy/standards , Immunosuppression Therapy/statistics & numerical data , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/etiology , Respiratory Syncytial Viruses/physiology , Roseolovirus Infections/epidemiology , Roseolovirus Infections/etiology , Transplantation, HomologousABSTRACT
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.
Subject(s)
Cytomegalovirus Infections/diagnosis , Donor Selection/standards , Epstein-Barr Virus Infections/diagnosis , Hematopoietic Stem Cell Transplantation/standards , Incidental Findings , Syphilis/diagnosis , Toxoplasmosis/diagnosis , Blood Donors , Consensus , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/blood , Epstein-Barr Virus Infections/blood , France , Health Knowledge, Attitudes, Practice , Herpesvirus 4, Human/isolation & purification , Humans , Immunoglobulin M/blood , Syphilis/blood , Syphilis/immunology , Toxoplasma/isolation & purification , Toxoplasmosis/blood , Transplantation, HomologousABSTRACT
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview on secondary adrenal insufficiency and osteoporosis post-transplant.
Subject(s)
Adrenal Insufficiency/therapy , Endocrine System Diseases/etiology , Endocrine System Diseases/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Osteoporosis/therapy , Adrenal Insufficiency/etiology , Adult , Bone Density , Child , Dietary Supplements , Diphosphonates/therapeutic use , Glucocorticoids/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Osteoporosis/etiology , Transplantation, Homologous , Vitamins/therapeutic useABSTRACT
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of common issues related to the donor: pre-transplant pregnancy and monoclonal gammopathy.
Subject(s)
Blood Donors , Donor Selection/standards , Health Knowledge, Attitudes, Practice , Hematopoietic Stem Cell Transplantation/standards , Incidental Findings , Paraproteinemias/diagnosis , Pregnancy Tests , Consensus , Female , Gestational Age , Humans , Paraproteinemias/blood , Pregnancy/blood , Pregnancy Complications/blood , Pregnancy Complications/prevention & controlABSTRACT
In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview on dyslipidemia and thyroid disorders post-transplant.
Subject(s)
Dyslipidemias/therapy , Endocrine System Diseases/etiology , Endocrine System Diseases/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Thyroid Diseases/therapy , Choice Behavior , Consensus , Diet , Dyslipidemias/etiology , Fibric Acids/therapeutic use , Hematopoietic Stem Cell Transplantation/standards , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Monitoring, Physiologic/methods , Monitoring, Physiologic/standards , Thyroid Diseases/etiology , Transplantation, HomologousABSTRACT
We report our experience on rituximab-cyclophosphamide-dexamethasone (RCD) combination therapy for the treatment of autoimmune disorders (AIDs) in 48 chronic lymphocytic leukemia (CLL) patients. Overall, 81% of patients were relapsing for AID after previous treatment with corticosteroids, splenectomy, rituximab or alemtuzumab. Diagnosis of AID was autoimmune hemolytic anemia (AIHA) in 26 (54%), autoimmune thrombocytopenia (AITP) in 9 (18.8%), Evan's syndrome in 8 (16.7%) and pure red cell aplasia (PRCA) in 5 patients (10.5%). Median time of autoimmune disorder (AID) onset from CLL diagnosis was 60 months (range: 0-240), and CLL was considered progressive in 40% of subjects upon AID diagnosis (complex AID). Median hemoglobin pre-treatment was 7.7 g/100 ml, and median platelet count 36.5 × 10(9)/l, returning to a median of 12.5 /100ml and 37.5 × 10(9)/l, respectively. Overall, an 89.5% response rate was obtained with this combination, irrespective of the AID type. Relapse occurred in 19 patients (39.6%). Median duration of response for autoimmunity (DR-AI) was 24 months, but DR-AI was higher for patients presenting: (1) AID early during CLL course (<3 years), or (2) both PRCA and AIHA. Median time to CLL progression in 48 patients was 16 months, but this time was statistically shorter for Evan's syndrome and AITP patients as compared with AIHA and PRCA patients. This study emphasizes the relevance of CLL-directed immune chemotherapy in the management of CLL-associated AID.
