Showing papers in "Bone Marrow Transplantation in 2009"
TL;DR: Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective are presented.
Abstract: Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective
339 citations
TL;DR: These guidelines on the management of HSV, VZV and EBV infection in patients with hematological malignancies and after SCT were prepared by the European Conference on Infections in Leukemia following a predefined methodology.
Abstract: These guidelines on the management of HSV, VZV and EBV infection in patients with hematological malignancies and after SCT were prepared by the European Conference on Infections in Leukemia following a predefined methodology. A PubMed search was conducted using the appropriate key words to identify studies pertinent to management of HSV, VZV and EBV infections. References of relevant articles and abstracts from recent hematology and SCT scientific meetings were also reviewed. Prospective and retrospective studies identified from the data sources were evaluated, and all data deemed relevant were included in this analysis. The clinical and scientific background was described and discussed, and the quality of evidence and level of recommendation were graded according to the Centers for Disease Control criteria.
334 citations
TL;DR: In this patient cohort, response to MSC transfusion was lower than in the series reported earlier, however, the experience supports the potential efficacy of MSC in the treatment of steroid-refractory aGVHD.
Abstract: Mesenchymal stem cells have been shown to mediate immunomodulatory effects. They have been used in patients with steroid-refractory acute GVHD (aGVHD), but their relevance as a therapeutic agent targeting aGVHD has still to be defined. In this case series, we report 13 patients with steroid-refractory aGVHD who received BM-derived MSC expanded in platelet lysate-containing medium from unrelated HLA disparate donors. MSC were characterized by their morphological, phenotypical and functional properties. All tested preparations suppressed the proliferation of in vitro activated CD4+ T cells. MSC were transfused at a median dosage of 0.9 x 10(6)/kg (range 0.6-1.1). The median number of MSC applications was 2 (range 1-5). Only two patients (15%) responded and did not require any further escalation of immunosuppressive therapy. Eleven patients received additional salvage immunosuppressive therapy concomitant to further MSC transfusions, and after 28 days, five of them (45%) showed a response. Four patients (31%) are alive after a median follow-up of 257 days, including one patient who initially responded to MSC treatment. In our patient cohort, response to MSC transfusion was lower than in the series reported earlier. However, our experience supports the potential efficacy of MSC in the treatment of steroid-refractory aGVHD.
299 citations
TL;DR: This poster presents a probabilistic procedure called “spot-spot aspiration aspiration aspiration” (SMAS) which is a simple and straightforward procedure to remove the tumour from the lung using a X-ray machine.
Abstract: Karolinska University Hospital, Stockholm, Sweden; Hopital Henri Mondor, Creteil, France; Universitatsklinik Wurzburg Medizinische Klinik und Poliklinik II, Wurzburg, Germany; University of Washington/Seattle Children’s Hospital and Regional Medical Center, Seattle, WA, USA; Institue of Tropical Medicine, Universidade de Sao Paulo, Sao Paulo, Brazil; Department of Medicine, Oncology, Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada and Memorial Sloan Kettering Cancer Center, New York, NY, USA
265 citations
TL;DR: The results of this pilot study show that infusion of ex-vivo culture-expanded haploidentical MSCs into unrelated pediatric UCBT recipients can be performed safely, and supports the investigation of unrelated ‘off the shelf’ allogeneic HLA-mismatched MSC products.
Abstract: Suboptimal neutrophil and platelet recovery after unrelated donor umbilical cord blood transplantation (UCBT) may be due in part to an impaired microenvironment after intensive chemoradiotherapy. In an attempt to speed hematopoietic recovery, 15 pediatric patients with high-risk acute leukemia were enrolled on a single-institution phase I-II clinical trial in which ex-vivo culture-expanded MSCs from haploidentical parental donors were infused at the time of UCBT. Eight patients received MSCs on day 0, with three patients having a second dose infused on day 21. No serious adverse events were observed with any MSC infusion. All eight evaluable patients achieved neutrophil engraftment at a median of 19 days. Probability of platelet engraftment was 75%, at a median of 53 days. With a median follow-up of 6.8 years, five patients remain alive and disease free. The results of this pilot study show that infusion of ex-vivo culture-expanded haploidentical MSCs into unrelated pediatric UCBT recipients can be performed safely. This encouraging safety profile with haploidentical MSCs supports the investigation of unrelated 'off the shelf' allogeneic HLA-mismatched MSC products.
251 citations
TL;DR: Improved strategies to mobilize stem cells would increase the availability of auto-HSCT and optimize engraftment and outcomes in patients with multiple myeloma or chemosensitive relapsed high- or intermediate-grade non-Hodgkin's lymphoma.
Abstract: Autologous hematopoietic SCT (auto-HSCT) provides hematopoietic support after high-dose chemotherapy and is the standard of care for patients with multiple myeloma (MM) or chemosensitive relapsed high- or intermediate-grade non-Hodgkin's lymphoma (NHL). However, yields of hematopoietic stem cells vary greatly between patients, and the optimal strategy to mobilize hematopoietic stem cells into peripheral blood for collection has not been defined. Current mobilization strategies consist of cytokines alone or in combination with chemotherapeutic agents. Cytokine-only mobilization regimens are well tolerated, but their utility is limited by suboptimal PBSC yields. When a myelosuppressive chemotherapeutic agent is added to a cytokine mobilization regimen, PBSC collections improve two- to five-fold. This benefit is tempered by increased toxicity, morbidity and resource utilization. All current regimens fail to mobilize sufficient hematopoietic stem cells to proceed to transplantation in 5-30% of patients, necessitating additional mobilization attempts or precluding transplantation, which may negatively affect patient outcomes and survival. Improved strategies to mobilize stem cells would increase the availability of auto-HSCT and optimize engraftment and outcomes in patients with MM or NHL. Novel agents used in conjunction with cytokines have the potential to increase PBSC collections without introducing additional morbidity, thereby improving patient outcomes.
212 citations
TL;DR: Assignment of a multimodal intervention during allo-HSCT did not cause untoward events, sustained aerobic capacity and muscle strength and reduced loss of functional performance during hospitalization and longitudinal changes in QOL, fatigue and psychological well-being favored the intervention group, but did not reach statistical significance.
Abstract: The aim of this randomized controlled trial was to investigate the effect of a 4- to 6-week multimodal program of exercise, relaxation and psychoeducation on physical capacity, functional performance and quality of life (QOL) in allogeneic hematopoietic cell transplantation (allo-HSCT) adult recipients. In all, 42 patients were randomized to a supervised multimodal intervention or to a control group receiving usual care. The primary end point was on aerobic capacity measured in VO(2) max. Secondary end points were muscle strength, functional performance, physical activity level, QOL, fatigue, psychological well-being and clinical outcomes. The multimodal intervention had a significant effect on physical capacity: VO(2) max (P<0.0001) and muscle strength: chest press (P<0.0001), leg extension (P=0.0003), right elbow flexor (P=0.0009), right knee extensor (P<0.0001) and functional performance (stair test) (0.0008). Moreover, the intervention group showed significantly better results for the severity of diarrhea (P=0.014) and fewer days of total parenteral nutrition (P=0.019). Longitudinal changes in QOL, fatigue and psychological well-being favored the intervention group, but did not reach statistical significance. Assignment of a multimodal intervention during allo-HSCT did not cause untoward events, sustained aerobic capacity and muscle strength and reduced loss of functional performance during hospitalization.
196 citations
TL;DR: Results of unrelated allogeneic cord blood transplants in malignant and nonmalignant diseases, in adults and children, show that, compared with HLA-matched unrelated BM transplant, cord blood has several advantages, including prompt availability of the transplant, decrease of GVHD and better long-term immune recovery resulting in a similar long- term survival.
Abstract: Since the first human cord blood transplant, performed 20 years ago, cord blood banks have been established worldwide for the collection and cryopreservation of cord blood for allogeneic hematopoietic stem cell transplant. A global network of cord blood banks and transplant centers has been established for a common inventory and study of clinical outcomes. Results of unrelated allogeneic cord blood transplants in malignant and nonmalignant diseases, in adults and children, show that, compared with HLA-matched unrelated BM transplant, cord blood has several advantages, including prompt availability of the transplant, decrease of GVHD and better long-term immune recovery resulting in a similar long-term survival. Several studies have shown that the number of cells is the most important factor for engraftment, although some degree of HLA mismatches is acceptable. Developments are expected to facilitate engraftment, including ex vivo expansion of stem cells, intrabone injection of cord blood cells and double cord blood transplants. In addition to hematopoietic stem cells, cord blood and placenta contain a large number of nonhematopoietic stem cells. In the absence of ethical concern, the unlimited supply of cells explains the increasing interest of using cord blood for developing regenerative medicine.
154 citations
TL;DR: Invasive aspergillosis (IA) is a serious complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT), particularly from donors other than HLA-identical sibling as mentioned in this paper.
Abstract: Invasive aspergillosis (IA) is a serious complication in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT), particularly from donors other than HLA-identical sibling. All 306 patients who underwent alternative donor HSCT between 01 January 1999 and 31 December 2006 were studied. Late IA was defined as occurring >or=40 days after HSCT. The median follow-up was 284 days (range, 1-2709). Donors were matched unrelated (n=185), mismatched related (n=69), mismatched unrelated (n=35) and unrelated cord blood (n=17). According to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, 2 patients already had IA at HSCT, 23 had early IA and 20 had late IA (IA incidence 15%). Eight patients had proven and 37 probable IA. Multivariate analyses showed that significant predictors of IA were delayed neutrophil engraftment, extensive chronic GVHD (cGVHD), secondary neutropenia and relapse after transplant. Early IA was associated with active malignancy at HSCT, CMV reactivation and delayed lymphocyte engraftment. Late IA was predicted by cGVHD, steroid therapy, secondary neutropenia and relapse after HSCT. IA-related mortality among IA patients was 67% and was influenced by use of anti-thymocyte globulin, steroids, higher levels of creatinine, and lower levels of IgA and platelets. The outcome of IA depends on the severity of immunodeficiency and the status of the underlying disease.
142 citations
TL;DR: This poster presents a poster presented at the European Society for Medical Oncology Congress (ES congress) in Basel, Switzerland, entitled “Advances in Hematology and Hepatology: Advances in Translation and Translation of Hematological Carcinoma Research.”
Abstract: City of Hope, Duarte, CA, USA; Brigham and Women’s Hospital, Boston, MA, USA; Department of Medicine, University of Washington Fred Hutchinson Cancer Research Center, Seattle, WA, USA; St George’s Hospital, London, UK; Universitatsklinik Wurzburg Medizinische Klinik und Poliklinik II, Wurzburg, Germany; Department of Hematology, Karolinska University Hospital, Stockholm, Sweden; Department of Gastroenterology/Hepatology, University of Washington, Seattle, WA, USA and Department of Biomedicine, University Hospital, Basel, Switzerland
136 citations
TL;DR: It is hoped that by ex vivo expansion of UCB, a resulting decrease in the morbidity and mortality ofUCB transplantation will be observed, and that the availability of additional cells may allow adoptive immunotherapy or gene transfer therapies in the UCB setting.
Abstract: A marked increase in the utilization of umbilical cord blood (UCB) transplantation has been observed in recent years; however, the use of UCB as a hematopoietic stem cell (HSC) source is limited primarily by the number of progenitor cells contained in the graft. Graft failure, delayed engraftment and profound delay in immune reconstitution lead to significant morbidity and mortality in adults. The lack of cells available for post transplant therapies, such as donor lymphocyte infusions, has also been considered to be a disadvantage of UCB. To improve outcomes and extend applicability of UCB transplantation, one potential solution is ex vivo expansion of UCB. Investigators have used several methods, including liquid suspension culture with various cytokines and expansion factors, co-culture with stromal elements and continuous perfusion systems. Techniques combining ex vivo expanded and unmanipulated UCB are being explored to optimize the initial engraftment kinetics as well as the long-term durability. The optimal expansion conditions are still not known; however, recent studies suggest that expanded UCB is safe. It is hoped that by ex vivo expansion of UCB, a resulting decrease in the morbidity and mortality of UCB transplantation will be observed, and that the availability of additional cells may allow adoptive immunotherapy or gene transfer therapies in the UCB setting.
TL;DR: It is concluded that metabolic syndrome occurs frequently among allogeneic HCT survivors who are seen by transplant physicians, and approaches to screening, prevention and management of metabolic syndrome should be developed for HCT recipients.
Abstract: We conducted a cross-sectional study to estimate the prevalence of metabolic syndrome, a clustering of risk factors associated with cardiovascular disease, among 86 adults who had allogeneic hematopoietic-cell transplant (HCT) as compared with 258 age- and gender-matched US population controls selected from the 2005-2006 National Health and Nutrition Examination Survey database. The median age at study enrollment was 50 years (range, 21-71), and patients were at a median of 3 years (range, 1-21) from HCT. The prevalence of metabolic syndrome was 49% (95% confidence intervals (CI), 38-60%) among HCT recipients, a 2.2-fold (95% CI, 1.3-3.6, P=0.002) increase compared with controls. The prevalence rates of elevated blood pressure and hypertriglyceridemia were significantly higher among HCT recipients than among controls, but the prevalence rates of abdominal obesity, elevated blood glucose and low high-density lipoprotein cholesterol were not. HCT survivors with metabolic syndrome were more likely to have microalbuminuria (43 vs 10%) and elevated creatinine (31 vs 11%). No patient, donor or transplant characteristics were associated with the diagnosis of metabolic syndrome. We conclude that metabolic syndrome occurs frequently among allogeneic HCT survivors who are seen by transplant physicians. Approaches to screening, prevention and management of metabolic syndrome should be developed for HCT recipients.
TL;DR: Background to hematopoietic cell transplantation, including post transplantimmune recovery, and post transplant immune recovery are studied.
Abstract: Background to hematopoietic cell transplantation, including post transplant immune recovery
TL;DR: Clinical trials are underway in Crohn's disease and multiple sclerosis and are being planned for systemic lupus erythematosus (SLE), systemic sclerosis, systemic vasculitis and other AD.
Abstract: MSCs, otherwise known as multipotent mesenchymal stromal cells, are being examined for the treatment of autoimmune disease (AD) on the basis of their in vitro antiproliferative properties, efficacy in animal models, apparent low acute toxicity and the early positive anecdotal outcomes in human acute GVHD. Phase I/II clinical trials are underway in Crohn's disease and multiple sclerosis (MS) and are being planned for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), systemic vasculitis and other AD. Open issues include patient selection, disease stage and activity, MSC source and expansion and long-term safety. Multidisciplinary groups are collaborating to ensure maximal use of available resources to establish the place, if any, of MSC in the treatment of AD.
TL;DR: Comparing the efficacy and safety of empirical plus PCR-based vs empirical liposomal amphotericin B treatment after Allo-SCT and no difference was observed in the incidence of IFI and survival between the two arms is observed.
Abstract: We compared the efficacy and safety of empirical plus PCR-based vs empirical liposomal amphotericin B treatment after Allo-SCT. Allo-SCT recipients were randomized to receive either PCR-based preemptive therapy (group A; n=198) or empirical antifungal therapy (group B; n=211) with liposomal amphotericin B. In group A, therapy was started after one positive PCR result or after 120 h of febrile neutropenia refractory to broad-spectrum antibacterial therapy. In group B, liposomal amphotericin B was started after 120 h of refractory febrile neutropenia. Demographic and clinical characteristics were well balanced. A total of 112 (57.1%) patients in group A and 76 (36.7%) patients in group B received antifungal therapy (P<0.0001). Twelve patients in group A and 16 patients in group B developed proven invasive fungal infection (IFI). Survival curves showed better survival until day 30 when close PCR monitoring was performed (mortality 1.5 vs 6.3%; P=0.015), but there was no difference at day 100. At day 100, no difference was observed in the incidence of IFI (primary end point) and survival between the two arms. Further studies are required to assess the benefit of using PCR in patients after SCT.
TL;DR: Outcomes of 716 patients with multiple myeloma who were mobilized using CY and growth factor or growth factor alone before SCT suggested that CY damaged the microenvironment and slowed engraftment, and by lengthening the period between the completion of apheresis and stem cell reinfusion, the micro environment may recover and result in faster engraftments.
Abstract: We retrospectively analyzed outcomes of 716 patients with multiple myeloma who were mobilized using CY and growth factor (n=370) or growth factor alone (n=346) before SCT. Patients receiving CY had higher stem cell yields than the growth factor only group (median number of apheresis sessions needed to achieve stem cell collection goals, two vs four sessions, respectively (P=0.001)). However, patients treated with CY required more time for engraftment of platelets and neutrophils (P<0.001 for both). For patients receiving CY, 75% achieved engraftment (defined as a platelet count of 50 x 10(9)/l) by day 39, whereas 75% of patients not receiving CY achieved engraftment by day 18. Similar results were observed for neutrophil engraftment. These differences did not affect the duration of hospitalization, but patients treated with CY had a higher incidence of post transplant nonstaphylococcal bacteremia. For CY-mobilized patients, considerably faster platelet engraftment (5 fewer days) resulted if stem cell reinfusion occurred more than 30 days after the first apheresis session. Our data suggested that CY damaged the microenvironment and slowed engraftment. By lengthening the period between the completion of apheresis and stem cell reinfusion, the microenvironment may recover and result in faster engraftment.
TL;DR: In conclusion, CBT with single units of relatively low cell content and 0–3 HLA mismatches is feasible as a first choice option for adult patients who lack a readily available adequate adult donor.
Abstract: This open label clinical study provides updated evaluation of the strategy of single unit cord blood transplants (CBTs) with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC). Fifty-five adults with high-risk hematological malignancies, median age 34 years (16–60 years) and weight 70 kg (43–95 kg), received CBTs (median 2.39 × 107 total nucleated cell (TNC) per kg and 0.11 × 106 CD34+ per kg) and TPD-MHSC (median 2.4 × 106 CD34+ per kg and 3.2 × 103 CD3+ per kg). Median time to ANC and to CB-ANC >0.5 × 109/l as well as to full CB-chimerism was 10, 21 and 44 days, with maximum cumulative incidences (MCI) of 0.96, 0.95 and 0.91. Median time to unsupported platelets >20 × 109/l was 32 days (MCI 0.78). MCI for grades I–IV and III–IV acute GVHD (aGVHD) were 0.62 and 0.11; 12 of 41 patients (29%) who are at risk developed chronic GVHD, becoming severely extensive in three patients. Relapses occurred in seven patients (MCI=0.17). The main causes of morbi-mortality were post-engraftment infections. CMV reactivations were the most frequent, their incidence declining after the fourth month. Five-year overall survival and disease-free survival (Kaplan–Meier) were 56 % and 47% (63% and 54% for patients ⩽40 years). In conclusion, CBT with single units of relatively low cell content and 0–3 HLA mismatches is feasible as a first choice option for adult patients who lack a readily available adequate adult donor.
TL;DR: Despite safety of administration, IBMI of one of two UCB units did not shorten the time to neutrophil engraftment and offers no advantage over conventional double unit transplantation.
Abstract: The time to neutrophil engraftment for adult patients after myeloablative double unit umbilical cord blood (UCB) transplantation is 23 days when the two units are given i.v. We hypothesized that the intra-BM injection (IBMI) of one of the two UCB units would reduce systemic loss of hematopoietic progenitors and shorten time to neutrophil recovery after myeloablation. Ten patients with a median age of 35 years were transplanted. The unit to be given by IBMI was randomly assigned; the other unit was given i.v. The median infused graft total nucleated cell dose was 3.7 × 107/kg with no difference between i.v. and IBMI units. All patients tolerated the procedure well, and there was no severe adverse event related to IBMI. The median time to neutrophil engraftment and plt recovery >50 000/μl was 21 and 69 days, respectively. In all, 9 of 10 patients engrafted, 5 with the i.v. unit and 4 with the IBMI unit; 7 of 8 evaluable patients developed acute GVHD and 5 of 10 patients died from treatment-related causes. Survival was 47% at 1 year. Despite safety of administration, IBMI of one of two UCB units did not shorten the time to neutrophil engraftment and offers no advantage over conventional double unit transplantation.
Journal Article•
TL;DR: Allografting conferred a long-term survival and disease-free advantage over standard autografts in this comparative study.
Abstract: Before the introduction of new drugs, we designed a trial where treatment of newly diagnosed myeloma patients was based on the presence or absence of HLA-identical siblings. First-line treatments included a cytoreductive autograft followed by a nonmyeloablative allograft or a second melphalan-based autograft. Here, we report long-term clinical outcomes and discuss them in the light of the recent remarkable advancements in the treatment of myeloma. After a median follow-up of 7 years, median overall survival (OS) was not reached (P = .001) and event-free survival (EFS) was 2.8 years (P = .005) for 80 patients with HLA-identical siblings and 4.25 and 2.4 years for 82 without, respectively. Median OS was not reached (P = .02) and EFS was 39 months (P = .02) in the 58 patients who received a nonmyeloablative allograft whereas OS was 5.3 years and EFS 33 months in the 46 who received 2 high-dose melphalan autografts. Among patients who reached complete remission in these 2 cohorts, 53% and 19% are in continuous complete remission. Among relapsed patients rescued with \"new drugs,\" median OS from the start of salvage therapy was not reached and was 1.7 (P = .01) years, respectively. Allografting conferred a long-term survival and disease-free advantage over standard autografting in this comparative study.
TL;DR: Reversible dasatinib-induced pulmonary arterial hypertension and right ventricle failure in a previously allografted CML patient is described.
Abstract: Reversible dasatinib-induced pulmonary arterial hypertension and right ventricle failure in a previously allografted CML patient
TL;DR: It is concluded that in well-selected patients, salvage auto-SCT is safe and effective for relapsed multiple myeloma.
Abstract: Therapeutic options for patients with multiple myeloma whose disease has relapsed after a prior auto-SCT include novel biologic therapies, traditional chemotherapy or a second transplant, with no clear standard of care. Few published studies address the safety and efficacy of a second auto-SCT for relapsed disease. We reviewed the Abramson Cancer Center experience with salvage auto-SCT for relapsed multiple myeloma. Forty-one patients had received a salvage auto-SCT at our institution; the median time between transplants was 37 months (range 3-91). The overall response rate in assessable patients was 55%, and treatment-related mortality was 7%. With a median follow-up time of 15 months, the median PFS was 8.5 months and the median overall survival (OS) was 20.7 months. In a multivariate analysis of OS, independent prognostic factors were >or=5 prior lines of therapy and time to progression after initial auto-SCT of
TL;DR: The 2007 report describes the current status of HSCT activity in Europe, highlights the increasing role of allogeneic HSCT in treatment of AML and gives the first quantitative information on novel cellular therapies.
Abstract: The 2007 report describes the current status of HSCT activity in Europe, highlights the increasing role of allogeneic HSCT in treatment of AML and gives the first quantitative information on novel cellular therapies. In 2007, there were 25 563 first HSCTs, 10 072 allogeneic (39%), 15 491 autologous (61%) and 3606 additional transplants reported from 613 centers in 42 countries. The main indications were leukemias (8061 (32%; 89% allogeneic)); lymphomas (14 627 (57%; 89% autologous)), solid tumors (1488 (6%; 96% autologous)) and nonmalignant disorders (1302 (5%; 91% allogeneic)). Peripheral blood was the main source of stem cells for autologous HSCT (98%) and the predominant source for allogeneic HSCT (71%). Among allogeneic HSCTs, the number of unrelated donor grafts equaled the number of HLA-identical sibling donor grafts for the first time (47% each). AML was the most frequent indication for allogeneic HSCT (32% of all allogeneic HSCTs), with an increase of 247 (8%). Information on novel cellular therapies was collected for the first time; there were 212 mesenchymal SCTs and 212 HSCTs for nonhematopoietic use. The indications for the latter were cardiovascular disorders (97; 46%), neurological disorders (94; 44%) and tissue repair (21; 10%). These data illustrate the expanding role of cellular therapies.
TL;DR: This analysis, undertaken in a contemporary cohort of related donor recipients, indicates that the consensus guidelines are applicable to this population of CGVHD patients.
Abstract: The Diagnosis and Staging Working Group of the NIH Consensus Development Project on Criteria for Clinical Trials in chronic GVHD (CGVHD) recently proposed criteria for diagnosis and assessment of overall CGVHD severity. We retrospectively reviewed 54 consecutive patients diagnosed with CGVHD between January 2002 and December 2005 after sibling donor transplant to assess the applicability of the new criteria in prognosticating survival and transplant-related mortality (TRM). A total of 8 patients (15%) were reclassified as late onset/persistent or recurrent acute GVHD (late aGVHD), 15 (28%) had overlap syndrome and 31 (57%) had classic CGVHD. Three-year overall survival was worse in patients with late aGVHD (3-year probability 25% (95% CI 4-56%)) followed by overlap syndrome (3-year probability 87% (95% CI 56-96%)) and CGVHD (3-year probability 75% (95% CI 54-87%)); P=0.001. Among patients with overlap syndrome and CGVHD, a trend towards worse survival was seen in patients with severe disease (3-year probability 57.3% (95% CI 21-82%)) as compared to mild+moderate disease (3-year probability 85.1% (95% CI 68-94)); P=0.1. This analysis, undertaken in a contemporary cohort of related donor recipients, indicates that the consensus guidelines are applicable to this population of CGVHD patients.
TL;DR: It is concluded that allografting after low-dose DAC and subsequent conditioning with FBM is feasible, with no unexpected toxicities and appears as a valid alternative to standard chemotherapy (‘InDACtion instead of induction’) in elderly patients with MDS/AML.
Abstract: Novel, non-intensive treatment options in older MDS/AML patients planned for allografting, with the goal of down-staging the underlying disease and bridging time to transplantation, are presently being developed. 5-azacytidine and decitabine (DAC) are of particular interest, as they can be given repetitively, with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses. We describe 15 consecutive patients (median age 69 years, range 60-75 years) with MDS (n=10) or AML (n=5) who all received first-line treatment with DAC and subsequent allografting (from sibling donor in four patients, unrelated donor in 11) after reduced-intensity conditioning with the FBM regimen. Successful engraftment was attained in 14/15 patients, all of whom achieved a CR, with a median duration of 5 months (range 1+ to 51+). Six of these 14 patients are alive (4 with complete donor chimerism), 8 have died either from relapse (n=4) or treatment-related complications while in CR (n=4). We conclude that allografting after low-dose DAC and subsequent conditioning with FBM is feasible, with no unexpected toxicities and appears as a valid alternative to standard chemotherapy ('InDACtion instead of induction') in elderly patients with MDS/AML.
TL;DR: Allogeneic HSCT can induce remission in patients suffering from refractory AD and provide the basis for carefully conducted prospective trials, according to the retrospective nature of this study and the heterogeneous, partly incomplete data.
Abstract: Allogeneic hematopoietic SCT (HSCT) has been used as treatment for single patients with autoimmune diseases (AD). To summarise currently available information, we analyzed all patients who underwent allogeneic HSCT for AD and who reported to the European Group for Blood and Marrow Transplantation (EBMT) database. Thirty-five patients receiving 38 allogeneic transplantations for various hematological and non-hematological AD were identified. Four patients had had an allogeneic HSCT for a conventional hematological indication in the past. Fifty-five per cent of the transplantation procedures led to a complete clinical response of the refractory AD and 23% to at least a partial response. The median duration of response at the last follow-up was 70.7 (15.2-130) months. Three patients relapsed at a median of 12.3 months after HSCT. Treatment-related mortality at 2 years was 22.1% (95% CI: 7.3-36.9%). Two deaths were caused by progression of AD. The probability of survival at 2 years was 70%. No single factor predicting the outcome could be identified. The retrospective nature of this study and the heterogeneous, partly incomplete data are its limitations. However, allogeneic HSCT can induce remission in patients suffering from refractory AD. These data provide the basis for carefully conducted prospective trials.
TL;DR: It is concluded that Wolman disease can be successfully treated with HCT, and that hepatic and cognitive function can be preserved with early diagnosis and timely referral to a transplant center.
Abstract: Wolman disease is the infantile form of autosomal recessive acid lipase deficiency, typically presenting in early infancy with diarrhea, massive hepatosplenomegaly, failure to thrive, and calcification of adrenal glands. Hematopoietic cell transplantation (HCT) is the only therapy reported to prevent hepatic failure and death, which without treatment occurs within the first year of life. We report a single institution's experience with HCT treatment of four Wolman patients, two of whom are long-term survivors (the longest survival reported to date, (4 and 11 years). Survivors showed resolution of diarrhea within weeks after engraftment, normalized hepatic function, improved hepatosplenomegaly, and in one patient normal adrenal function. The older patient has normal adaptive functions but mild to moderate neurocognitive deficiencies thought to be secondary to treatment and other medical problems. The younger patient has age-appropriate neurodevelopmental and adaptive abilities. We conclude that Wolman disease can be successfully treated with HCT, and that hepatic and cognitive function can be preserved with early diagnosis and timely referral to a transplant center.
TL;DR: It is concluded thatMTX–CsA and MTX–tacrolimus are both acceptable alternatives for GVHD prophylaxis, although MTX-tacralimus may be superior in terms of aGVHD reduction.
Abstract: Opinions are divided regarding the best prophylactic regimen for GVHD. The aim of this study was to evaluate potential survival benefit of different prophylactic regimens for acute GVHD (aGVHD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) including patients undergoing Allo-SCT. We included trials that assessed the addition of MTX, compared CsA and tacrolimus and evaluated the addition of steroids. Outcomes assessed were all-cause mortality (ACM) at the longest follow-up, aGVHD, chronic GVHD, TRM, relapse rate and regimen-specific adverse events. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled. The regimen of MTX-CsA vs CsA alone (four trials) yielded no statistically significant difference in ACM (RR=0.84 (0.61-1.14)), but a significant decrease in aGVHD (RR=0.52 (0.39-0.7)). There was no difference in ACM for the comparison of MTX-CsA and MTX-tacrolimus (three trials); however, MTX-tacrolimus was superior to MTX-CsA in the reduction of aGVHD (RR=0.62 (0.52-0.75)) and severe aGVHD (RR=0.67 (0.47-0.95)). The addition of steroids did not affect the outcomes (four trials). We conclude that MTX-CsA and MTX-tacrolimus are both acceptable alternatives for GVHD prophylaxis, although MTX-tacrolimus may be superior in terms of aGVHD reduction.
TL;DR: The area under the curve plasma concentrations of mycophenolic acid seemed to be suboptimal among patients with acute GVhd but not among those with chronic GVHD, and MMF can be used effectively for treatment of GV HD.
Abstract: We evaluated the pharmacokinetics and efficacy of oral mycophenolate mofetil (MMF) for treatment of refractory GVHD. In a prospective study of acute GVHD, 9 of 19 patients (47%) had a response and 10 (53%) had no improvement. Survival at 6 and 12 months after the start of MMF was 37 and 16%, respectively. In a retrospective study of acute GVHD, 14 of 29 patients (48%) had a response and 15 (52%) had no improvement. Survival at 6 and 12 months was 55 and 52%, respectively. In a prospective study of chronic GVHD, the cumulative incidence of disease resolution and withdrawal of all systemic immunosuppressive treatment was 9, 17 and 26% at 12, 24 and 36 months, respectively, after starting MMF. Thirteen patients (59%) required additional systemic immunosuppressive treatment for chronic GVHD. Nine of the 42 patients (21%) in the prospective studies discontinued MMF treatment because of toxicity. The area under the curve plasma concentrations of mycophenolic acid seemed to be suboptimal among patients with acute GVHD but not among those with chronic GVHD. MMF can be used effectively for treatment of GVHD.
TL;DR: Both CD4 and CD8 CMV-specific immune reconstitution is required for protection from recurrent activation, and measurement of the magnitude of the CMv-specific CD4+ immune response is useful in managing viral reactivation following HSCT.
Abstract: Reactivation of CMV is a common complication following allogeneic haematopoietic SCT and is associated with significant morbidity and mortality. The relative importance of the CD4+ and CD8+ components of the CMV-specific immune response in protection from reactivation is unclear. The CMV-specific CD4+ and CD8+ immune response was measured at serial time points in 32 patients following allogeneic HSCT. Intracellular cytokine staining following CMV lysate stimulation and HLA-peptide tetramers were used to determine CMV-specific CD4+ and CD8+ responses, respectively. A deficient CMV-specific CD4+ T-cell immune response within the first 30-50 days post transplant was associated with high risk of viral reactivation. Patients with combined impairment of the CD4+ and CD8+ immune response within the first 100 days were susceptible to late viral reactivation. The frequency of CMV-specific CD4+ T cells correlated with CMV-specific CD8+ T cells, comprising 10% of the whole T-cell repertoire. Early CMV-specific CD4+ T-cell reconstitution was dominated by effector memory cells with normal levels of IL-2 resuming 6 months following transplantation. In summary, both CD4 and CD8 CMV-specific immune reconstitution is required for protection from recurrent activation. Measurement of the magnitude of the CMV-specific CD4+ immune response is useful in managing viral reactivation following HSCT.
TL;DR: This study aims to demonstrate the efforts towards in-situ applicability of EMMARM, which aims to provide real-time information about the immune response of the immune system to disease.
Abstract: School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Haematology Program, University of Manitoba, Winnipeg, Manitoba, Canada; Centers for Disease Control and Prevention, Atlanta, GA, USA; Center for Hematology, Oncology and Radiotherapy, Klinikum Ernst von Bergmann, Potsdam, Germany; Hopital Saint-Louis, Paris, France; Division of Infectious Disease, Roswell Park Cancer Institute, Buffalo, NY, USA; Pediatric Infectious Disease, Duke University Medical Center, Durham, NC, USA; Department of Hematology and Oncology, University of Florida, Gainesville, FL, USA and Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil