Comparison of SF3B1/DNMT3A Comutations With DNMT3A or SF3B1 Mutation Alone in Myelodysplastic Syndrome and Clonal Cytopenia of Undetermined Significance.

OBJECTIVES: To compare the clinical significance of SF3B1/DNMT3A Comutations with SF3B1 or DNMT3A mutation alone in myelodysplastic syndrome (MDS) and clonal cytopenia of undetermined significance (CCUS). METHODS: We identified and compared 31 patients with only DNMT3A mutation, 48 patients with only SF3B1 mutation, and 16 patients with only SF3B1/DNMT3A comutations. RESULTS: SF3B1/DNMT3A comutations were found to be more common in MDS, whereas DNMT3A mutation alone was more common in CCUS. The patients with SF3B1/DNMT3A comutations were less likely to have poor cytogenetics than patients with DNMT3A mutation alone. Patients with SF3B1/DNMT3A comutations showed significantly longer median survival time and better overall survival than patients with DNMT3A mutation alone. CONCLUSIONS: Patients with SF3B1/DNMT3A comutations appear to have better clinical outcomes than patients with isolated DNMT3A mutation. These findings suggest that the favorable prognosis of SF3B1 mutation in is not abrogated by the concurrent presence of a DNMT3A mutation.

Long-term overall- and progression-free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non-Hodgkin lymphoma.

In a prospective phase II trial, pentostatin combined with cyclophosphamide and rituximab (PCR) induced strong responses and was well-tolerated in previously untreated patients with advanced-stage, indolent non-Hodgkin lymphoma (iNHL). After a median patient follow-up of more than 108 months, we performed an intent-to-treat analysis of our 83 participants. Progression-free survival (PFS) rates at 108 months for follicular lymphoma (FL), marginal zone lymphoma (MZL) and small lymphocytic lymphoma (SLL) were 71%, 67% and 15%, respectively, and were affected by clinicopathological characteristics. Ten-year PFS rates for those with beta-2-microglobulin levels <2·2 and ≥2·2 mg/l prior to treatment were 71% and 21%, respectively. Patients without bone marrow involvement had 10-year PFS rates of 72% vs. 29% for those with involvement. At time of analysis, the median overall survival (OS) had not been reached. The OS rate was 64% at 10 years and differed significantly based on histology: 94% for FL, 66% for MZL and 39% for SLL. Long-term toxicities included 18 (21·7%) patients with second malignancies and 2 (2·4%) who developed myelodysplastic syndrome after receiving additional lines of chemotherapy. Our 10-year follow-up analysis confirms that PCR is an effective, robust and tolerable treatment regimen for patients with iNHL.

The Hematopoietic Cell Transplant Comorbidity Index predicts survival after allogeneic transplant for nonmalignant diseases.

Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases.

Post-transplant lymphoproliferative disease may be an adverse risk factor for patient survival but not graft loss in kidney transplant recipients.

Better prognostication of graft and patient outcomes among kidney transplant recipients with post-transplant lymphoproliferative disease (PTLD) in the rituximab era is needed to inform treatment decisions. Therefore, we sought to estimate the excess risks of death and graft loss in kidney transplant recipients with PTLD, and to determine risk factors for death. Using the ANZDATA registry, the risks of mortality and graft loss among recipients with and without PTLD were estimated using survival analysis. A group of 367 patients with PTLD (69% male, 85% white, mean age 43 years) were matched 1 to 4 to 1468 controls (69% male, 88% white, mean age 43 years), and followed for a mean of 16 years. Recipients with PTLD experienced poorer 10-year patient survival (41%, 95% confidence intervals 36-47%) than controls (65%, 63-68%). Excess mortality occurred in the first 2 years post-transplant (hazard ratio 8.5, 6.7-11), but not thereafter (1.0, 0.76-1.3). Cerebral lymphoma (2.0, 1.3-3.1), bone marrow disease (2.0, 1.2-3.3) and year of diagnosis prior to 2000 (2.2, 1.4-3.5; after 2000 reference) were risk factors of death. PTLD did not confer an excess risk of graft loss (1.08, 0.69-1.70). Thus, PTLD is a risk factor for death, particularly in the first two years after diagnosis. Cerebral or bone marrow diseases were associated with increased mortality risk, but overall survival in the rituximab era (post 2000) has improved.

Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up.

The National Cancer Institute Inherited Bone Marrow Failure Syndromes Cohort enrolls patients with the four major syndromes: Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome, and follows them with a common comprehensive protocol. The current analysis includes more than double the numbers of patients and person-years since our first report, published in 2010. Patients with Fanconi anemia and dyskeratosis congenita developed head and neck and anogenital squamous cell carcinomas at rates that were hundreds-fold greater than those of the general population. In competing risk analyses the cumulative incidence of severe bone marrow failure, leading to stem cell transplantation or death, was more than 70% by age 60. Patients with Diamond-Blackfan anemia developed lung, colon, and cervical cancer at rates greater than those of the general population. The cumulative incidence of severe bone marrow failure in those with Diamond-Blackfan anemia was 50% by age 60. The smaller group, with Shwachman-Diamond syndrome, have not as yet developed a significant number of solid tumors, but 40% developed bone marrow failure by age 50. The risk of solid tumors following stem cell transplantation in Fanconi anemia and in dyskeratosis congenita was significantly higher than in non-transplanted patients. There was no clear association of genotype with cancer in any of the syndromes. Cancer was most common in Fanconi anemia, followed by dyskeratosis congenita; Diamond-Blackfan anemia and Shwachman-Diamond syndrome are less cancer-prone, but nonetheless all patients are at increased risks of bone marrow failure and specific cancers. clinicaltrials.gov Identifier: 00027274.

Clinical outcomes of unrelated cord blood transplantation in children with malignant and non-malignant diseases: Multicenter experience in China.

This multicenter retrospective study included 184 children with malignant and non-malignant diseases who underwent UCBT between January 1998 and August 2012. The malignant disease group included 101 children with ALL, AML, CML, JMML, and MDS, and the non-malignant disease group included 83 children with PID, ß-thalassemia, IMD BMF, and HLH. The median duration to neutrophil and platelet engraftment was 16 and 35 days in the malignant disease group vs 15 and 38 days in the non-malignant disease group. The cumulative incidence of grade II-IV aGVHD and cGVHD was 25.6% and 13.5% in the malignant disease group vs 19.7% and 11.1% in the non-malignant disease group, respectively. The median duration and cumulative incidence of neutrophil and platelet engraftment, and the cumulative incidence of grade II-IV aGVHD and cGVHD were similar between the two groups. Of the 184 pediatric patients, 114 patients survived during a median follow-up period of 14 months (range 4-138). The 5-year OS and DFS were not statistically different between the two groups (56.3% and 46.1% in malignant disease group vs 68.5% and 52.8% in non-malignant disease group). The above results indicate that UCB is a viable source for HSCT for children with malignant or non-malignant diseases, especially in urgent cases.

Rapamycin is highly effective in murine models of immune-mediated bone marrow failure.

Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually with anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In this study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure. Rapamycin ameliorated pancytopenia, improved bone marrow cellularity, and extended animal survival in a manner comparable to the standard dose of cyclosporine. Rapamycin effectively reduced Th1 inflammatory cytokines interferon-γ and tumor necrosis factor-α, increased the Th2 cytokine interleukin-10, stimulated expansion of functional regulatory T cells, eliminated effector CD8+ T cells (notably T cells specific to target cells bearing minor histocompatibility antigen H60), and preserved hematopoietic stem and progenitor cells. Rapamycin, but not cyclosporine, reduced the proportion of memory and effector T cells and maintained a pool of naïve T cells. Cyclosporine increased cytoplasmic nuclear factor of activated T-cells-1 following T-cell receptor stimulation, whereas rapamycin suppressed phosphorylation of two key signaling molecules in the mammalian target of rapamycin pathway, S6 kinase and protein kinase B. In summary, rapamycin was an effective therapy in mouse models of immune-mediated bone marrow failure, acting through different mechanisms to cyclosporine. Its specific expansion of regulatory T cells and elimination of clonogenic CD8+ effectors support its potential clinical utility in the treatment of aplastic anemia.

Prognostic significance of focal lesions and diffuse infiltration on MRI for multiple myeloma: a meta-analysis.

OBJECTIVES: MRI of bone marrow of the axial skeleton is recommended for evaluation of multiple myeloma. The impact of bone marrow involvement pattern on MRI for determining progression-free survival (PFS) and overall survival (OS) is not yet clear. METHODS: We performed a meta-analysis of research on the prognostic significance of MRI patterns for OS and PFS using a random effects model. Databases searched without language restriction were MEDLINE, EMBASE, and the Cochrane Library (January 1976 to April 2014). Manual searches were also conducted. RESULTS: Of 10,953 citations identified in the original search, 10 cohort studies for a total of 2015 patients met the inclusion criteria. Nine of the 10 included studies are from three research groups. Pooled hazard ratios were 1.80 (95 % confidence interval [CI] 1.32-2.46; P < 0.001) for OS and 2.30 (95 % CI 1.65-3.20; P < 0.001) for PFS for focal lesions on MRI; and 1.70 (95 % CI 1.30-2.21; P < 0.001) for OS and 1.74 (95 % CI 1.07-2.85; P = 0.03) for PFS for diffuse infiltration on MRI. No significant heterogeneity was observed among studies. CONCLUSIONS: This meta-analysis demonstrated an association between focal lesions and diffuse infiltration and poor prognosis in this population. KEY POINTS: • MRI findings of multiple myeloma include normal, focal, variegated and diffuse infiltration • Focal lesions and diffuse infiltration on MRI were poor prognostic factors • Bone marrow involvement pattern on MRI can help physicians assess prognosis.

Aplasia medular secundaria a la infección por el virus del dengue / Medullary aplastic anemia secondary to dengue virus infections

La aplasia medular es una enfermedad hematológica caracterizada por citopenia periférica y una marcada hipocelularidad medular. Esta es una rara complicación de infecciones como la fiebre hemorrágica del dengue. Se presentan 2 pacientes en edad pediátrica que fueron atendidas en el servicio de Pediatría del Instituto de Hematología e Inmunología con el diagnóstico de aplasia medular en el transcurso de una infección por dengue (IgM+). Ambos casos tuvieron diagnóstico histológico de aplasia medular muy grave con una evolución tórpida(AU)

Aplastic anemia is a blood disorder characterized by peripheral cytopenia and marked marrow hypocellularity. This is a rare complication of infections, such as dengue hemorrhagic fever. Two pediatric patients were referred to our center with the diagnosis of aplastic anemia in the course of infection by dengue (IgM +), both with severe pancytopenia(AU)

Reduced-intensity conditioning with fludarabine and busulfan for allogeneic hematopoietic cell transplantation in elderly or infirm patients with advanced myeloid malignancies.

We report a retrospective single-center analysis of 112 consecutive patients that underwent allogeneic hematopoietic cell transplantation (HCT) after reduced-intensity conditioning (RIC) with fludarabine (FLU) and busulfan (BU) for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and myeloproliferative syndrome (MPS) from 2005 to 2014. Three-year event-free survival (EFS) and overall survival (OS) were 46 and 58 %, respectively. Patients ≥60 years of age showed a similar outcome compared to younger patients (3-year OS 55 vs. 61 %, p = 0.96; 3-year EFS 46 vs. 46 %, p = 0.82). Cumulative incidence of non-relapse mortality (NRM) at 3 years adjusted for relapse as competing risk was 25 % for patients aged <60 years and 15 % for older patients (p = 0.15). Infusions of higher CD34(+) blood stem cell doses were associated with a significantly better outcome in the elderly subgroup (3-year OS 82 vs. 39 %, p = 0.007). Moreover, complete donor chimerism at day +100 was associated with a significantly improved survival (3-year OS 69 vs. 23 %, p = 0.003). In conclusion, our data suggest that RIC with FLU/BU enables long-term disease-free survival even in an elderly patient population. Age has no negative impact on the outcome of allogeneic HCT, and decision for transplant should be based on disease risk and performance status rather than age alone.

Loss of c-Kit and bone marrow failure upon conditional removal of the GATA-2 C-terminal zinc finger domain in adult mice.

Heterozygous mutations in the transcriptional regulator GATA-2 associate with multilineage immunodeficiency, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). The majority of these mutations localize in the zinc finger (ZnF) domains, which mediate GATA-2 DNA binding. Deregulated hematopoiesis with GATA-2 mutation frequently develops in adulthood, yet GATA-2 function in the bone marrow remains unresolved. To investigate this, we conditionally deleted the GATA-2 C-terminal ZnF (C-ZnF) coding sequences in adult mice. Upon Gata2 C-ZnF deletion, we observed rapid peripheral cytopenia, bone marrow failure, and decreased c-Kit expression on hematopoietic progenitors. Transplant studies indicated GATA-2 has a cell-autonomous role in bone marrow hematopoiesis. Moreover, myeloid lineage populations were particularly sensitive to Gata2 hemizygosity, while molecular assays indicated GATA-2 regulates c-Kit expression in multilineage progenitor cells. Enforced c-Kit expression in Gata2 C-ZnF-deficient hematopoietic progenitors enhanced myeloid colony activity, suggesting GATA-2 sustains myelopoiesis via a cell intrinsic role involving maintenance of c-Kit expression. Our results provide insight into mechanisms regulating hematopoiesis in bone marrow and may contribute to a better understanding of immunodeficiency and bone marrow failure associated with GATA-2 mutation.

Contribution of comorbidities and grade of bone marrow fibrosis to the prognosis of survival in patients with primary myelofibrosis.

The widely used current International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) is based on clinical parameters. The objective of this study was to identify additional prognostic factors at the time of diagnosis, which could have an impact on the future treatment of patients with PMF. We conducted a study of 131 consecutive PMF patients with median follow-up of 44 months. Data on baseline demographics, clinical and laboratory parameters, IPSS, grade of bone marrow fibrosis (MF), as well as influence of concomitant comorbidities were analyzed in terms of survival. Comorbidity was assessed using the Adult Comorbidity Evaluation-27 (ACE-27) score and the hematopoietic cell transplantation comorbidity index. An improved prognostic model of survival was obtained by deploying the MF and ACE-27 to the IPSS. A multivariable regression analyses confirmed the statistical significance of IPSS (P<0.001, HR 3.754, 95% CI 2.130-6.615), MF>1 (P=0.001, HR 2.694, 95% CI 1.466-4.951) and ACE-27 (P<0.001, HR 4.141, 95% CI 2.322-7.386) in predicting the survival of patients with PMF. When the IPSS was modified with MF and ACE-27, the final prognostic model for overall survival was stratified as low (score 0-1), intermediate (score 2-3) and high risk (score 4-6) with median survival of not reached, 115 and 22 months, respectively (P<0.001). Our findings indicate that the combination of histological changes, comorbidity assessment and clinical parameters at the time of diagnosis allows better discrimination of patients in survival prognostic groups and helps to identify high-risk patients for a poor outcome.

Mycobacterial bone marrow infections at a medical centre in Taiwan, 2001-2009.

Mycobacterial bone marrow (BM) infection is the most common diagnosis established by BM examinations for fever of unknown origin. In this study, clinical features and outcomes of patients who fulfilled the criteria for BM infection due to Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) at a medical centre in Taiwan from 2001 to 2009 were investigated. The BM histopathological findings were also analysed. A total of 24 patients (16 men, eight women) with mycobacterial BM infections were found. Of these, nine (38%) were positive for human immunodeficiency virus (HIV) and six (25%) had no pre-existing immunocompromised conditions. MTB isolates were obtained from 11 (46%) patients and NTM species were isolated from 10 (42%) patients, including M. avium complex (MAC, n = 7) and M. kansasii (n = 3). Patients with MTB infections were significantly older than those with NTM infections (60·5 vs. 47·7 years, P = 0·043) and were less likely to have a positive BM culture (45% vs. 100%, P = 0·012). The 90-day survival rates for MTB and NTM BM infections were 68% and 60%, respectively (P = 0·61). In addition, the presence of BM granulomas was significantly more common in patients with MTB BM infections than in those with NTM infections (82% vs. 30%, P = 0·030). In Taiwan, the importance of NTM was not inferior to MTB and besides MAC, M. kansasii might be an important pathogen in non-HIV-infected patients. The presence of BM granulomas and caseation provides valuable information regarding early treatment pending culture results.

Peripheral-blood stem cells versus bone marrow from unrelated donors.

BACKGROUND: Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS: We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS: The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS: We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome.

BACKGROUND: Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. DESIGN AND METHODS: One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20 × 10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. RESULTS: Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. CONCLUSIONS Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.

Predicting survival of patients with hypocellular myelodysplastic syndrome: development of a disease-specific prognostic score system.

BACKGROUND: Although most patients with myelodysplastic syndrome (MDS) exhibit bone marrow hypercellularity, a subset of them present with a hypocellular bone marrow. Specific factors associated with poor prognosis have not been investigated in patients with hypocellular MDS. METHODS: The authors studied a cohort of 253 patients with hypocellular MDS diagnosed at The University of Texas MD Anderson Cancer Center between 1993 and 2007 and a cohort of 1725 patients with hyper-/normocellular MDS diagnosed during the same time period. RESULTS: Patients with hypocellular MDS presented more frequently with thrombocytopenia (P < .019), neutropenia (P < .001), low serum ß-2 microglobulin (P < .001), increased transfusion dependency (P < .001), and intermediate-2/high-risk disease (57% vs 42%, P = .02) compared with patients with hyper-/normocellular MDS. However, no difference in overall survival was observed between the 2 groups (P = .28). Multivariate analysis identified poor performance status (Eastern Cooperative Oncology Group ≥2), low hemoglobin (<10 g/dL), unfavorable cytogenetics (-7/7q or complex), increased bone marrow blasts (≥5%), and high serum lactate dehydrogenase (>600 IU/L) as adverse independent factors for survival. CONCLUSIONS: A new prognostic model based on these factors was built that segregated patients into 3 distinct risk categories independent of International Prognostic Scoring System (IPSS) score. This model is independent from the IPSS, further refines IPSS-based prognostication, and may be used to develop of risk-adapted therapeutic approaches for patients with hypocellular MDS.

Reduced mortality after allogeneic hematopoietic-cell transplantation.

BACKGROUND: Over the past decade, advances have been made in the care of patients undergoing transplantation. We conducted a study to determine whether these advances have improved the outcomes of transplantation. METHODS: We analyzed overall mortality, mortality not preceded by relapse, recurrent malignant conditions, and the frequency and severity of major complications of transplantation, including graft-versus-host disease (GVHD) and hepatic, renal, pulmonary, and infectious complications, among 1418 patients who received their first allogeneic transplants at our center in Seattle in the period from 1993 through 1997 and among 1148 patients who received their first allogeneic transplants in the period from 2003 through 2007. Components of the Pretransplant Assessment of Mortality (PAM) score were used in regression models to adjust for the severity of illness at the time of transplantation. RESULTS: In the 2003-2007 period, as compared with the 1993-1997 period, we observed significant decreases in mortality not preceded by relapse, both at day 200 (by 60%) and overall (by 52%), the rate of relapse or progression of a malignant condition (by 21%), and overall mortality (by 41%), after adjustment for components of the PAM score. The results were similar when the analyses were limited to patients who received myeloablative conditioning therapy. We also found significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs. CONCLUSIONS: We found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).

Utility of the psychosocial assessment of candidates for transplantation (PACT) scale in allogeneic BMT.

The psychosocial assessment of candidates for transplantation (PACT) scale was completed before the transplant on 120 patients who underwent allogeneic transplant from November 2003 to June 2007. The PACT has eight subscales, each rated on a 5-point scale, and an initial and final rating independently based on the rater's overall impressions of the candidate's acceptability for transplant. This exploratory study assessed the clinical utility of the PACT scale for psychosocial screening in allogeneic BMT. Associations of the PACT subscales and the final rating with sixteen post transplant medical outcomes were examined using the Jonchkheere-Terpstra test, the Cochran-Armitage test or the Cox proportional hazards analysis. Significant relationships (P