ABSTRACT
Therapeutic donor lymphocyte infusions (tDLI) are used to reinforce the graft-versus-leukemia (GvL) effect in relapse after allogeneic stem cell transplantation (alloSCT). In contrast, the role of prophylactic DLI (proDLI) in preventing leukemia relapse has been less clearly established, although supported by retrospective, case-control, and registry analyses. We report a prospective, monocentric, ten year cohort of patients with high risk acute leukemias (AL) or myelodysplasia (MDS) in whom proDLI were applied beyond day +120 post alloSCT to compensate for lack of GvL.272 consecutive allotransplanted AL or MDS patients in complete remission and off immunosuppression at day +120 were stratified according to the prior appearance of relevant GvHD (acute GvHD °II-IV or extensive chronic GvHD) as a clinical indicator for GvL. Escalating doses of unmodified proDLI were applied to 72/272 patients without prior relevant GvHD. Conversely, 157/272 patients with prior spontaneous GvHD did not receive proDLI, nor did 43/272 patients with contraindications (uncontrolled infections, patient refusal, DLI unavailability).By day 160-landmark analysis (median day of first DLI application), proDLI recipients had significantly higher five-year overall (OS) and disease free survival (DFS) (77% and 67%) than patients with spontaneous GvHD (54% and 53%) or with contraindications (46% and 45%) (p=0.003). Relapse incidence for patients with proDLI (30%) or spontaneous GvHD (29%) was significantly lower than in patients with contraindications (39%; p=0.021). With similar GvHD incidence beyond day +160, non-relapse mortality (NRM) was less with proDLI (5%) than without proDLI (18%; p=0.036).In conclusion, proDLI may be able to compensate for lack of GvL in alloSCT recipients with high risk AL or MDS.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Secondary Prevention , Retrospective Studies , Prospective Studies , Lymphocyte Transfusion/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Leukemia, Myeloid, Acute/complications , Myelodysplastic Syndromes/therapy , Myelodysplastic Syndromes/complications , Chronic Disease , LymphocytesABSTRACT
Sickle cell disease is a rare, but complex multi-systemic disorder with high need of interdisciplinary and specialized care and new structural requirements. Besides care of those chronically sick patients, transition process is a vulnerable phase which highly influences further treatment. To make matters worse, patients often have migration background with subsequent communication problems. A national guidance for a standardized transition process is lacking in Germany. In context of a structured consensus process, the "transition initiative sickle cell disease" developed specific recommendations for a structured transition of sickle cell patients on the basis of the S3 transition guideline of the DGfTM. These recommendations should improve this vulnerable process in this complex disease to ensure adequate further treatment and to avoid acute and chronic complications but also mental, social or job-related issues. Besides improvement of quality of life, medical treatment and survival, health economic aspects arise. Documents were developed to support and facilitate the transition process and are available under www.sichelzellkrankheit.info/transition/.
Subject(s)
Anemia, Sickle Cell , Humans , Anemia, Sickle Cell/therapy , Germany , Transition to Adult Care , Practice Guidelines as TopicABSTRACT
Sickle cell disease (SCD) is considered a rare disease in Germany. Due to the increasing prevalence, the acute and chronic morbidities associated with the disease and the sharp increase in the mortality rate of young adults, a need-based transition structure for patients with SCD in Germany is explicitly required. This is the first multicenter German consensus statement addressing the importance of implementing a standardized transition guideline that allows adolescents and young adults to safely transition from pediatric to adult care. Early identification of medical needs and intervention remains important in the context of chronic diseases. Effective measures can improve health care in general, as they lead to a reduction in disease and the consequential economic burden. It is noteworthy that improving structural barriers remains a key challenge even in highly developed countries such as Germany. Inclusion of these transition services for patients with SCD into the regular care of chronically ill adolescents and young adults should be ensured, as well as the coverage of costs associated with a structured transition process.
Subject(s)
Graft vs Host Disease/drug therapy , Lung Diseases/complications , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Adult , Benzamides , Chronic Disease , Female , Graft vs Host Disease/pathology , Humans , Imatinib Mesylate , Lung Diseases/therapy , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation , Pilot Projects , Prospective Studies , Protein-Tyrosine Kinases/antagonists & inhibitors , Salvage Therapy , Treatment Outcome , Young AdultABSTRACT
Valganciclovir (VGC), an oral prodrug of ganciclovir (GCV), has been shown to clear cytomegalovirus (CMV) viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT), apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79%) than non-VGC therapies (69%). The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss) requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients), we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%), we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0-66)) compared to non-VGC (25 days (0-115)), without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity.
ABSTRACT
A phase 1 diagnostic study was performed to evaluate a novel technology for clinical proteomic research based on capillary electrophoresis and mass spectrometry. Urine from 40 patients after hematopoietic stem cell transplantation (HSCT; 35 allogeneic, 5 autologous) and 5 patients with sepsis was collected for a period of 100 days and analyzed. More than 1000 different polypeptides could be detected in individual samples. Polypeptide patterns excreted in the urine of patients were significantly different from those of healthy volunteers. No significant differences were detected comparing different conditioning regimens. The aim of this study was to identify polypeptide patterns functioning as early indicators of graft-versus-host disease (GVHD). Eighteen patients developed GVHD after allogeneic HSCT. Sixteen differentially excreted polypeptides formed a pattern of early GVHD markers, allowing discrimination of GVHD from patients without complications with 82% specificity and 100% sensitivity, cross-validated. Inclusion of 13 sepsis-specific polypeptides allowed us to distinguish sepsis from GVHD with a specificity of 97% and a sensitivity of 100%. Sequencing 2 prominent GVHD-indicative polypeptides led to the identification of a peptide from leukotriene A4 hydrolase and a peptide from serum albumin. The data reveal that capillary electrophoresis and mass spectrometry allow identification of biomarkers for a variety of diseases or related complications.