Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 42
Filter
1.
Transplant Cell Ther ; 29(3): 151-163, 2023 03.
Article in English | MEDLINE | ID: mdl-36442770

ABSTRACT

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplantation (HCT) associated with significant morbidity and mortality. However, TA-TMA is a clinical diagnosis, and multiple criteria have been proposed without universal application. Although some patients have a self-resolving disease, others progress to multiorgan failure and/or death. Poor prognostic features also are not uniformly accepted. The lack of harmonization of diagnostic and prognostic markers has precluded multi-institutional studies to better understand incidence and outcomes. Even current interventional trials use different criteria, making it challenging to interpret the data. To address this urgent need, the American Society for Transplantation and Cellular Therapy, Center for International Bone Marrow Transplant Research, Asia-Pacific Blood and Marrow Transplantation, and European Society for Blood and Marrow Transplantation nominated representatives for an expert panel tasked with reaching consensus on diagnostic and prognostic criteria. The panel reviewed literature, generated consensus statements regarding diagnostic and prognostic features of TA-TMA using the Delphi method, and identified future directions of investigation. Consensus was reached on 4 key concepts: (1) TA-TMA can be diagnosed using clinical and laboratory criteria or tissue biopsy of kidney or gastrointestinal tissue; however, biopsy is not required; (2) consensus diagnostic criteria are proposed using the modified Jodele criteria with additional definitions of anemia and thrombocytopenia. TA-TMA is diagnosed when ≥4 of the following 7 features occur twice within 14 days: anemia, defined as failure to achieve transfusion independence despite neutrophil engraftment; hemoglobin decline by ≥1 g/dL or new-onset transfusion dependence; thrombocytopenia, defined as failure to achieve platelet engraftment, higher-than-expected transfusion needs, refractory to platelet transfusions, or ≥50% reduction in baseline platelet count after full platelet engraftment; lactate dehydrogenase (LDH) exceeding the upper limit of normal (ULN); schistocytes; hypertension; soluble C5b-9 (sC5b-9) exceeding the ULN; and proteinuria (≥1 mg/mg random urine protein-to-creatinine ratio [rUPCR]); (3) patients with any of the following features are at increased risk of nonrelapse mortality and should be stratified as high-risk TA-TMA: elevated sC5b-9, LDH ≥2 times the ULN, rUPCR ≥1 mg/mg, multiorgan dysfunction, concurrent grade II-IV acute graft-versus-host disease (GVHD), or infection (bacterial or viral); and (4) all allogeneic and pediatric autologous HCT recipients with neuroblastoma should be screened weekly for TA-TMA during the first 100 days post-HCT. Patients diagnosed with TA-TMA should be risk-stratified, and those with high-risk disease should be offered participation in a clinical trial for TA-TMA-directed therapy if available. We propose that these criteria and risk stratification features be used in data registries, prospective studies, and clinical practice across international settings. This harmonization will facilitate the investigation of TA-TMA across populations diverse in race, ethnicity, age, disease indications, and transplantation characteristics. As these criteria are widely used, we expect continued refinement as necessary. Efforts to identify more specific diagnostic and prognostic biomarkers are a top priority of the field. Finally, an investigation of the impact of TA-TMA-directed treatment, particularly in the setting of concurrent highly morbid complications, such as steroid-refractory GVHD and infection, is critically needed.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Thrombotic Microangiopathies , Humans , Child , Prognosis , Bone Marrow , Prospective Studies , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/pathology , Hematopoietic Stem Cell Transplantation/adverse effects
5.
Bone Marrow Transplant ; 52(4): 580-587, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27991894

ABSTRACT

We hypothesized that IV busulfan (Bu) dosing could be safely intensified through pharmacokinetic (PK-) dose guidance to minimize the inter-patient variability in systemic exposure (SE) associated with body-sized dosing, and that this should improve outcome of AML/MDS patients undergoing allogeneic stem cell transplantation. To test this hypothesis, we treated 218 patients (median age 50.7 years, male/female 50/50%) with fludarabine 40 mg/m2 once daily x4, each dose followed by IV Bu, randomized to 130 mg/m2 (N=107) or PK-guided to average daily SE, AUC of 6000 µM min (N=111), stratified for remission status and allo-grafting from HLA-matched donors. Toxicity and GvHD rates in the groups were similar; the risk of relapse or treatment-related mortality remained higher in the fixed-dose group throughout the 80-month observation period. Further, PK-guidance yielded safer disease control, leading to improved overall and PFS, most prominently in MDS patients and in AML patients not in remission at allogeneic stem cell transplantation. We conclude that AML/MDS patients receiving pretransplant conditioning treatment with our 4-day regimen may benefit significantly from PK-guided Bu dosing. This could be considered an alternative to fixed-dose delivery since it provides the benefit of precise dose delivery to a predetermined SE without increasing risk(s) of serious toxicity and/or GvHD.


Subject(s)
Busulfan/administration & dosage , Drug Monitoring/methods , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Vidarabine/analogs & derivatives , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/toxicity , Busulfan/pharmacokinetics , Busulfan/toxicity , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/mortality , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Recurrence , Survival Analysis , Transplantation Conditioning/mortality , Transplantation, Homologous/mortality , Treatment Outcome , Vidarabine/administration & dosage
6.
Bone Marrow Transplant ; 52(1): 28-33, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27595282

ABSTRACT

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.


Subject(s)
Bendamustine Hydrochloride/administration & dosage , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Transplantation Conditioning/methods , Adult , Aged , Cyclophosphamide/administration & dosage , Disease-Free Survival , Female , Humans , Male , Middle Aged , Rituximab/administration & dosage , Survival Rate , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives
8.
Am J Transplant ; 16(5): 1492-502, 2016 05.
Article in English | MEDLINE | ID: mdl-26608093

ABSTRACT

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine-Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.


Subject(s)
BK Virus/pathogenicity , Graft vs Host Disease/mortality , Hematologic Diseases/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Kidney Diseases/mortality , Polyomavirus Infections/mortality , Tumor Virus Infections/mortality , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft vs Host Disease/etiology , Hematologic Diseases/complications , Hematologic Diseases/therapy , Humans , Infant , Infant, Newborn , Kidney Diseases/virology , Kidney Function Tests , Male , Middle Aged , Polyomavirus Infections/virology , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Transplantation, Homologous , Tumor Virus Infections/virology , Young Adult
10.
Ann Oncol ; 26(12): 2490-5, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26416896

ABSTRACT

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) and its common variants mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are rare extranodal non-Hodgkin's lymphomas. Patients who present with advanced disease and large-cell transformation (LCT) are incurable with standard treatments. In this article, we report the largest single-center experience with allogeneic stem-cell transplantation (SCT) for advanced CTCL. PATIENTS AND METHODS: This is a prospective case series of 47 CTCL patients who underwent allogeneic SCT after failure of standard therapy between July 2001 and September 2013. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) curves. The method of Fine and Gray was used to fit regression models to the same covariates for these cumulative incidence data. RESULTS: The Kaplan-Meier estimates of OS and PFS at 4 years were 51% and 26%, respectively. There was no statistical difference in the OS in patients who had MF alone, SS, MF with LCT, or SS with LCT. PFS at 4 years was superior in patients who had SS versus those who did not (52.4% versus 9.9%; P = 0.02). The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 40% and 28%, respectively. The cumulative nonrelapse mortality rate was 16.7% at 2 years. CONCLUSION: Allogeneic SCT may result in long-term remissions in a subset of patients with advanced CTCL. Although post-SCT relapse rates are high, many patients respond to immunomodulation and achieve durable remissions. CLINICALTRIALSGOV: NCT00506129.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/therapy , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Adult , Aged , Disease-Free Survival , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/trends , Humans , Male , Middle Aged , Prospective Studies , Transplantation, Homologous/methods , Transplantation, Homologous/trends , Young Adult
11.
Leukemia ; 29(11): 2126-33, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26293647

ABSTRACT

The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age <70 years should be considered as candidates for allo-SCT. Patients with intermediate-1-risk disease and age <65 years should be considered as candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood (PB) >2%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2- or high-risk disease lacking an human leukocyte antigen (HLA)-matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted.


Subject(s)
Hematopoietic Stem Cell Transplantation , Primary Myelofibrosis/therapy , Donor Selection , Histocompatibility Testing , Humans , Primary Myelofibrosis/mortality , Transplantation Conditioning , Transplantation, Homologous
12.
Bone Marrow Transplant ; 50 Suppl 2: S55-62, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26039209

ABSTRACT

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specific T-cells or chimeric-antigen receptor T-cells which are reviewed in this study.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft Enhancement, Immunologic/methods , Graft Survival , Graft vs Host Disease/prevention & control , Tissue Engineering/methods , Humans
14.
Bone Marrow Transplant ; 50(3): 420-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25531284

ABSTRACT

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.


Subject(s)
Aminocaproic Acid/administration & dosage , Hematopoietic Stem Cell Transplantation/adverse effects , Hemorrhage/drug therapy , Lung Diseases/drug therapy , Pulmonary Alveoli/blood supply , Steroids/administration & dosage , Female , Hematopoietic Stem Cell Transplantation/methods , Hemorrhage/diagnosis , Hemorrhage/etiology , Humans , Lung Diseases/etiology , Male , Middle Aged , Pulmonary Alveoli/drug effects , Retrospective Studies , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods
15.
Bone Marrow Transplant ; 49(11): 1352-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25089599

ABSTRACT

Myeloproliferative neoplasms are a category of diseases that have been traditionally amenable to allogeneic hematopoietic progenitor cell transplantation. Current developments in drug therapy have delayed transplantation for more advanced phases of the disease, especially for patients with CML, whereas transplantation remains a mainstream treatment modality for patients with advanced myelofibrosis and chronic myelomonocytic leukemia. Reduced-intensity conditioning has decreased the treatment-related mortality, and advances in the use of alternative donors for transplantation could extend the use of this procedure to an increasing number of patients with improved safety and efficacy. Here we review the current knowledge about allogeneic transplantation for myeloproliferative neoplasms and discuss the most important aspects to be considered when contemplating transplantation for patients with these diseases. Janus kinase 2 inhibitors offer the promise to improve spleen size and performance of patients with myelofibrosis and extend transplantation for patients with more advanced disease.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Primary Myelofibrosis/therapy , Protein Kinase Inhibitors/therapeutic use , Transplantation Conditioning/methods , Allografts , Hematologic Neoplasms/enzymology , Humans , Janus Kinase 2/antagonists & inhibitors , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Primary Myelofibrosis/enzymology
16.
Bone Marrow Transplant ; 49(8): 1036-41, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24887378

ABSTRACT

Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age <60 years, induction therapy with novel agents, kidney only involvement and Auto-SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.


Subject(s)
Amyloidosis/mortality , Amyloidosis/therapy , Stem Cell Transplantation , Adult , Aged , Aged, 80 and over , Autografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Immunoglobulin Light Chains , Male , Middle Aged , Time Factors
19.
Bone Marrow Transplant ; 48(9): 1218-23, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23503529

ABSTRACT

Disseminated adenoviral infection (AI) is associated with profound immunosuppression and poor outcome after allogeneic hematopoietic SCT (allo-HSCT). A better understanding of AI in allo-HSCT recipients can serve as a basis to develop more effective management strategies. We evaluated all adult patients who received allo-HSCT at MD Anderson Cancer Center between 1999 and 2008. Among the 2879 allo-HSCT patients, 73 (2.5%) were diagnosed with AI. Enteritis (26%) and pneumonia (24%) were the most common clinical manifestations; pneumonia was the most common cause of adenovirus-associated death. A multivariable Bayesian logistic regression showed that when the joint effects of all covariates were accounted for, cord blood transplant, absolute lymphocyte count (ALC) ≤ 200/mm(3) and male gender were associated with a higher probability of disseminated AI. The OS was significantly worse for patients with AI that was disseminated rather than localized (median of 5 months vs median of 28 months, P<0.001) and for patients with ALC ≤ 200/mm(3) (P<0.001). Disseminated AI, in patients who received allo-HSCT, is a significant cause of morbidity and mortality. Strategies for early diagnosis and intervention are essential, especially for high-risk patients.


Subject(s)
Adenoviridae Infections/etiology , Adenoviridae/isolation & purification , Hematopoietic Stem Cell Transplantation/adverse effects , Transplantation Conditioning/adverse effects , Adenoviridae Infections/immunology , Adenoviridae Infections/pathology , Adult , Aged , Aged, 80 and over , Female , HLA Antigens/immunology , Humans , Male , Middle Aged , Retrospective Studies , Transplantation, Homologous , Treatment Outcome , Young Adult
20.
Bone Marrow Transplant ; 48(1): 26-31, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22732703

ABSTRACT

We investigated the administration of i.v. BU combined with melphalan (Mel) in patients with ALL undergoing allogeneic hematopoietic SCT. Forty-seven patients with a median age of 33 years (range 20-61) received a matched sibling (n=27) or matched unrelated donor transplant (n=20) for ALL in first CR (n=26), second CR (n=13), or with more advanced disease (n=8). BU was infused daily for 4 days, either at a fixed dose of 130 mg/m² (5 patients) or using pharmacokinetic (PK) dose adjustment (42 patients), to target an average daily area-under-the-curve (AUC) of 5000 µmol/min, determined by a test dose of i.v. BU at 32 mg/m². This was followed by a rest day, then two daily doses of Mel at 70 mg/m². Stem cells were infused on the following day. The 2-year OS, PFS and non-relapse mortality (NRM) rates were 35% (95% confidence interval (CI), 23-51%), 31% (95% CI, 21-48%) and 37% (95% CI, 23-50%), respectively. Acute NRM at 100 days was favorable at 12% (95% CI, 5-24%); however, the 2-year NRM was significantly higher for patients older than 40 years, 58% vs 20%, mainly due to GVHD.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Busulfan/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Melphalan/therapeutic use , Myeloablative Agonists/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation Conditioning , Adult , Age Factors , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Busulfan/administration & dosage , Busulfan/adverse effects , Drug Therapy, Combination/adverse effects , Female , Follow-Up Studies , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Humans , Incidence , Infusions, Intravenous , Male , Melphalan/adverse effects , Middle Aged , Myeloablative Agonists/administration & dosage , Myeloablative Agonists/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/prevention & control , Secondary Prevention , Survival Analysis , Texas , Transplantation Conditioning/adverse effects , Transplantation, Homologous , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...