IgD Subtype But Not IgM or Non-Secretory Is a Prognostic Marker for Poor Survival Following Autologous Hematopoietic Cell Transplantation in Multiple Myeloma. Results From the EBMT CALM (Collaboration to Collect Autologous Transplant Outcomes in Lymphomas and Myeloma) Study.

BACKGROUND: The Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study has provided an opportunity to evaluate the real-world outcomes of patients with myeloma. The aim of this study was to compare the outcome according to the different subtypes of myeloma using CALM data. PATIENTS: This study compared overall survival (OS), progression-free survival (PFS), and complete remission (CR) and the impact of novel versus non-novel drug containing induction regimens prior to autologous hematopoietic cell transplantation (HCT) of 2802 patients with "usual" and "rare" myelomas. RESULTS: Our data suggest that IgM and non-secretory myeloma have superior PFS and OS compared with IgD myeloma and outcomes comparable to those for usual myeloma. Patients who received novel agent induction had higher rates of CR prior to transplant. Non-novel induction regimens were associated with inferior PFS but no difference in OS. Although not the primary focus of this study, we show that poor mobilization status is associated with reduced PFS and OS, but these differences disappear in multivariate analysis suggesting that poor mobilization status is a surrogate for other indicators of poor prognosis. CONCLUSION: We confirm that IgD myeloma is associated with the worst prognosis and inferior outcomes compared with the other isotypes.

Trasplante autólogo de progenitores hematopoyéticos en el Linfoma de Hodgkin / Autologous hematopoietic stem cell transplantation in Hodgkin's Lymphoma

Introducción: El trasplante autólogo de progenitores hematopoyéticos es una terapéutica aplicable en determinadas situaciones a pacientes con Linfoma de Hodgkin. Objetivo: Evaluar la respuesta al trasplante autólogo de progenitores hematopoyéticos en los pacientes con Linfoma de Hodgkin. Métodos: Se realizó un estudio de 60 pacientes con Linfoma de Hodgkin trasplantados en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, entre 1991 y 2018. Se estimó el porcentaje de respuesta a los tres meses, la supervivencia global y la supervivencia libre de enfermedad a los cinco años. Resultados: La tasa de respuesta a los tres meses fue de 82,7 por ciento. La supervivencia global y libre de enfermedad a los cinco años fue de 94,7 por ciento y 51,7 por ciento, respectivamente. La mortalidad temprana relacionada con el trasplante fue de 5 por ciento. Conclusiones: La aplicación del trasplante autólogo de progenitores hematopoyéticos constituyó una alternativa terapéutica válida. La baja mortalidad temprana evidenció una realización del procedimiento con un perfil de seguridad satisfactorio(AU)

Introduction: Autologous hematopoietic stem cell transplantation is an applicable therapy in certain situations to patients with Hodgkin's Lymphoma. Objective: To evaluate the response to autologous hematopoietic stem cell transplantation in patients with Hodgkin's Lymphoma. Methods: A study of 60 patients with Hodgkin lymphoma transplanted at Hermanos Ameijeiras Clinical and Surgical Hospital was carried out from 1991 to 2018. The percentage of response at three months, overall survival and disease-free survival period were estimated at five years. Results: The response rate at three months was 82.7 percent. Overall and disease-free survival at five years was 94.7 percent and 51.7 percent, respectively. Early transplant-related mortality was 5 percent. Conclusions: The use of autologous hematopoietic stem cell transplantation was a valid therapeutic alternative. The low early mortality evidenced that the procedure was performed with a satisfactory safety profile(AU)

The Choice of Pulmonary Autograft in Aortic Valve Surgery: A State-of-the-Art Primer.

The Ross procedure has long been seen as an optimal operation for a select few. The detractors of it highlight the issue of an additional harvesting of the pulmonary artery, subjecting the native PA to systemic pressures and the need for reintervention as reasons to avoid it. However, the PA is a living tissue and capable of adapting and remodeling to growth. We therefore review the current evidence available to discuss the indications, contraindications, harvesting techniques, and modifications in a state-of-the-art narrative review of the PA as an aortic conduit. Due to the lack of substantial well-designed randomized controlled trials (RCTs), we also highlight the areas of need to reiterate the importance of the Ross procedure as part of the surgical armamentarium.

Nutritional status as a predictor of adverse events and survival in pediatric autologous stem cell transplant.

Nutritional status is recognized as an independent and modifiable risk factor of outcome in stem cell transplant. Our research aim was to evaluate the impact of body mass index (BMI) and serum albumin on the prevalence of adverse events and survival in autologous transplant in children. A retrospective study was conducted of autologous transplants performed between 2006 and 2017 in the Children's Hospital Zagreb, Croatia. Nutritional status was assessed at the times of diagnosis, procedure, and discharge using BMI (underweight, normal, obese) and serum albumin (grades 1-4). Adverse events (fever, gastrointestinal toxicity, electrolyte disturbances, dysglycemia) and outcome (3-year, relapse, mortality) were documented. Seventy-seven children (54.5% males, mean age 7.9 years) underwent autologous transplant, mostly for neuroblastoma. In terms of BMI and albumin, which showed significant positive correlation at diagnosis (p = 0.026) and transplant (p = 0.016), most participants were well nourished. Average post-transplant weight loss was 4%. Major toxicities were severe mucositis (72.7%) and hypophosphatemia (31.2%). Relapse and mortality rates were 35.1% and 42.9%, respectively. Hypokalemia (p = 0.041) and hypomagnesemia (p = 0.044) were more prevalent in the underweight group, while obese children experienced significantly less severe mucositis (p = 0.016) and hypophosphatemia (p = 0.038). There was no significant difference regarding outcome among children of different nutritional status, although undernourished children tended to have lower relapse and mortality rates. In conclusion, underweight children are significantly more prone to severe electrolyte disorders and mucositis, and although statistical significance was not reached, are more likely to survive.

Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study.

BACKGROUND: The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation. METHODS: In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m2 administered orally on days 1-4) and prednisone (60 mg/m2 administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m2), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m2 either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. FINDINGS: Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2-67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3-64·5] vs 41·9 months [37·5-46·9]; hazard ratio [HR] 0·73, 0·62-0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3-49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0-not estimable] vs 45·5 months [39·5-58·4]; HR 0·77, 0·63-0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). INTERPRETATION: This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. FUNDING: Janssen and Celgene.

Autologous hematopoietic cell transplantation for acute myeloid leukemia in adults: 25 years of experience in Japan.

Autologous hematopoietic cell transplantation (HCT) has not gained universal popularity in the treatment of acute myeloid leukemia (AML), and its status remains unclear. To determine the implementation status and outcomes of autologous HCT for adults with AML in Japan, we analyzed data from 1,174 patients (including 446 with acute promyelocytic leukemia [APL]) who underwent autologous HCT between 1992 and 2016 consecutively reported to the Japanese nationwide transplantation registry. The annual number of transplantations peaked at 82 cases in 1997, and has recently remained at around 40 cases. The percentage of APL has increased sharply since 2004, and currently exceeds 70%. While most non-APL patients underwent autologous HCT during first complete remission (CR), transplantation during second CR has become mainstream for APL patients since the early 2000s. The 5-year survival, relapse, and non-relapse mortality rates were 55.3%, 42.1%, and 8.6% for non-APL patients, and 87.6%, 12.9%, and 3.4% for APL patients, respectively. Patients transplanted in the later period showed better survival than those transplanted in the earlier period, both for non-APL (P < 0.001) and APL (P = 0.036). These results clearly show the various changes in transplantation practice and post-transplant outcomes in Japan over the past 25 years.

Tandem high-dose chemotherapy with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin regimens for pediatric high-risk brain tumors.

BACKGROUND: High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan-thiotepa-carboplatin and melphalan-etoposide-carboplatin (TTC/MEC) regimens in pediatric brain tumors. METHODS: We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens. RESULTS: Eleven patients aged < 3 years at diagnosis were eligible for HDC/auto-SCT to avoid or defer radiotherapy. In addition, nine patients with high-risk medulloblastoma (presence of metastasis and/or postoperative residual tumor ≥ 1.5 cm2), eight with other high-risk brain tumor (six CNS primitive neuroectodermal tumor, one CNS atypical teratoid/rhabdoid tumor, and one pineoblastoma), and five with relapsed brain tumors were enrolled. There were three toxic deaths, and two of which were due to pulmonary complications. The main reason for not performing tandem auto-SCT was due to toxicities and patient refusal. The event-free survival (EFS) and overall survival (OS) rates of all patients were 59.4% and 80.0% at a median follow-up with 49.1 months from the first HDC/auto-SCT, respectively. The EFS/OS rates of patients aged < 3 years at diagnosis, high-risk medulloblastoma, other high-risk brain tumor, and relapsed tumors were 50.0/81.8%, 87.5/85.7%, 66.7/88.9%, and 20.0/60.0%, respectively. CONCLUSIONS: Although tandem HDC/auto-SCT with TTC/MEC regimens showed promising survival rates, treatment modifications are warranted to reduce toxicities. The survival rates with relapsed brain tumors were unsatisfactory despite HDC/auto-SCT, and further study is needed.

Long-term performance of pulmonary homografts after the Ross procedure: experience up to 25 years.

OBJECTIVES: The aim of this study was to evaluate the long-term durability and function of pulmonary homografts used for right ventricular outflow tract reconstruction in the Ross procedure at a single centre with 25 years of experience. METHODS: The study included 274 patients (212 male patients and 62 female patients; age 3-59 years), who underwent the Ross procedure between 1991 and 2014. Homograft-related complications and reinterventions were assessed. Homograft haemodynamic function was determined using transthoracic echocardiography undertaken by a single cardiologist. RESULTS: The all-cause 30-day mortality was 1.1% (3 patients), and there were 17 late deaths. One death was associated with a homograft-related complication. During the observation period (median 13.3 years; 3327.5 cumulative patient-years), 21 patients (7.7%) underwent at least 1 right ventricular outflow tract reintervention. Freedom from homograft reintervention was 95.6%, 90.4% and 87.5% at 10, 15 and 20 years, respectively. Paediatric patients had a significant lower rate of freedom from reintervention (log-rank P < 0.001). Remarkably, all patients who underwent reintervention were male (log-rank P = 0.009). Female patients received homografts with a significantly higher (P < 0.001) indexed diameter than male patients, which might be causally related to absent reinterventions in women. The linearized rate of homograft endocarditis was 0.2% per patient-year. At the latest echocardiography (median follow-up time 14.7 years; 164 patients), the peak transhomograft pressure gradient was <40 mmHg in 150 patients (91.5%), and homograft incompetence was none or trivial in 111 patients (67.7%), mild in 49 patients (29.9%) and moderate in 3 patients (1.8%). In 1 patient (0.6%), it was not possible to determine the degree of incompetence. Younger patient age (P < 0.001), a smaller homograft diameter (P = 0.014) and an increase in the body surface area during the follow-up time (P = 0.006) were significantly correlated with a higher peak transhomograft pressure gradient. Men had a significantly higher peak transhomograft pressure gradient than women (P = 0.018). CONCLUSIONS: Pulmonary homografts provide very satisfying long-term results after the Ross procedure. Differences in long-term performance are related to undersizing and young age.

Long-term results after the Ross procedure with the decellularized AutoTissue Matrix P® bioprosthesis used for pulmonary valve replacement.

OBJECTIVES: Since 1967, the Ross procedure has been performed to treat aortic valve disease using homografts for pulmonary valve replacement. The decellularized Matrix P® prosthesis was developed to overcome (some) limitations of homografts. Until now, the long-term outcome data have been unavailable. METHODS: Between 2002 and 2010, the Ross procedures using the Matrix P prosthesis were performed in 492 adult patients (mean age 57.2 ± 10.6 years, range 21-73 years) at our institution. Patient data were prospectively collected and analysed (3617.3 patient-years, mean follow-up 7.7 ± 4.3 years). Completeness of follow-up at 1, 5 and 10 years was 98.4%, 94.5% and 91.0%, respectively. RESULTS: Hospital mortality was 3.9% (n = 19). During follow-up, 121 patients died resulting in a survival rate at 5, 10 and 12.5 years of 82.8 ± 1.7%, 70.4 ± 2.3% and 62.4 ± 2.9%, respectively. Echocardiography revealed a high incidence of relevant dysfunction of the Matrix P prosthesis and subsequent right ventricular failure. Primary reoperation/reintervention was necessary for 150 Matrix P and 48 autografts. Freedom from pulmonary valve reoperation at 5, 10 and 12.5 years was 76.2 ± 2.1%, 58.6 ± 2.9% and 53.4 ± 3.4%, respectively. The autograft function and the left ventricular function showed similar results as previously reported with a freedom from autograft reoperation at 5, 10 and 12.5 years of 91.8 ± 1.4%, 86.1 ± 2.0% and 86.1 ± 2.0%, respectively. CONCLUSIONS: The Matrix P prosthesis used for the right ventricular outflow tract reconstruction in the Ross procedure showed unfavourable long-term echocardiographic results with a high rate of reoperation/reintervention for structural pulmonary valve failure. As a consequence, long-term survival of this patient cohort was impaired. Based on these findings, the use of the Matrix P prosthesis for pulmonary valve replacement for Ross procedures in adults should not be recommended.

Safety and survival outcomes for bloodless transplantation in patients with myeloma.

High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are established components in the treatment of multiple myeloma; however, undergoing transplantation usually requires hematopoietic support, which poses a challenge among patients who are unwilling to receive blood products. Most transplant centers decline HDT/ASCT to these patients because of safety concerns. Here, the authors' institutional data on safety, engraftment parameters, and survival outcomes after bloodless ASCT (BL-ASCT) are examined among patients with myeloma. This retrospective case-control study included patients who underwent BL-ASCT and Transfusion-supported ASCT (TS-ASCT) at Emory University Hospital between August 2006 and August 2016. In total, 24 patients who underwent BL-ASCT and 70 who underwent TS-ASCT were included. The median time for neutrophil engraftment, platelet engraftment and the median length of hospital stay all were equivalent for both groups. There were no transplant-related cardiovascular complications or mortality in either the BL-ASCT group or the TS-ASCT group. The median progression-free survival was 36 months and 44 months in the BL-ASCT and TS-ASCT groups, respectively (P = .277), and the median OS was not reached in either group at a median follow-up of 59 months after ASCT (P = .627). There was no transplant-related mortality at the 100-day or 1-year mark in either group. BL-ASCT is safe and feasible; transplant-related mortality, cardiovascular and hematologic complications are similar to those associated with TS-ASCT. Furthermore, BL-ASCT can yield similar engraftment and survival parameters comparable to those observed with TS-ASCT.

Impact of renal impairment on outcomes after autologous stem cell transplantation in multiple myeloma: a multi-center, retrospective cohort study.

BACKGROUND: Renal impairment (RI) is a negative prognostic factor in Multiple Myeloma (MM) and affected patients are often excluded from autologous stem cell transplantation (ASCT). However, it remains unclear whether historically inferior outcome data still hold true. METHODS: From a total of 475 eligible MM patients who had undergone ASCT between 1998 and 2016, 374 were included in this multi-centric retrospective cohort study. Renal function was determined both at the time of MM diagnosis and ASCT by estimated glomerular filtration rate (eGFR according to the MDRD formula, RI defined as eGFR < 60 ml/min/1.73m2). Patients were categorized into 3 groups: A) no RI diagnosis and ASCT, B) RI at diagnosis with normalization before ASCT and C) RI both at the time of diagnosis and ASCT. Log-rank testing was used for overall and progression-free survival (OS, PFS) analysis. CONCLUSION: While severe RI at MM diagnosis confers a risk of shorter OS, MM progression after ASCT is not affected by any stage of renal failure. It can be concluded that ASCT can be safely carried out in MM patients with mild to moderate RI and should be pro-actively considered in those with severe RI. RESULTS: When comparing all groups, no difference in OS and PFS was found (p = 0.319 and p = 0.904). After further stratification according to the degree of RI at the time of diagnosis, an OS disadvantage was detected for patients with an eGFR < 45 ml/min/m2. PFS was not affected by any RI stage.

Impact of a Composite Valved RV-PA Graft After Stage 1 Palliation.

BACKGROUND: The use of a valved right ventricular to pulmonary artery shunt (RVPAS) has been reported by some to improve pulmonary artery growth after stage 1 palliation (S1P). METHODS: We retrospectively reviewed all patients undergoing an S1P with an RVPAS between January 2013 and May 2017, stratified by RVPAS type: a ring-reinforced polytetrafluoroethylene (PTFE) graft or a composite graft that included a distal valved femoral or saphenous vein homograft. We examined the association of RVPAS type on postoperative hemodynamics, time to reintervention, pulmonary artery growth, and survival. RESULTS: Among 94 infants, 56 (60%) underwent PTFE-only shunt, 24 (25%) underwent femoral vein homograft, and 14 (15%) underwent saphenous vein homograft, and no relevant risk factor differences were found between the groups. Arterial saturation was 2.3% higher (p = 0.014) and serum lactic acid was 1.24 mg/dL lower (p = 0.03) in the femoral vein homograft group than in the PTFE-only group, although venous saturation was similar. By 60 days, 50% of patients with saphenous vein homograft had a reintervention compared with 5% with PTFE graft (p < 0.0001) and 12% with femoral vein homograft (p = 0.2 versus PTFE). At the time of stage 2 palliation, no differences were found in pulmonary artery size or growth over time by either echocardiogram or angiography or in the density of aortopulmonary collaterals or degree of tricuspid regurgitation. The 12-month survival was similar between the groups. CONCLUSIONS: The use of an interposition femoral vein homograft into the RVPAS may enhance perioperative stability, but it does not substantially improve interstage growth of the pulmonary arteries. Use of saphenous vein homograft is associated with earlier time to reintervention after S1P.

Autologous Stem Cell Transplantation for Patients with Early Progression of Follicular Lymphoma: A Follow-Up Study of 2 Randomized Trials from the German Low Grade Lymphoma Study Group.

Patients with follicular lymphoma (FL) and progression of disease (POD) within 24 months after frontline treatment (POD24) have poor overall survival (OS). The optimal salvage treatment for these patients is unknown. We assessed the role of high-dose therapy and autologous stem cell transplantation (ASCT) in transplant-eligible patients. We analyzed 162 patients with advanced-stage FL who had received frontline treatment within the GLSG1996 or GLSG2000 trials. All patients had POD at age ≤ 65 years and had not received a prior transplant. Second-line treatment was not specified by study protocols. Survival was calculated from time of second-line treatment. Eighteen patients (11%) progressed (n = 16) or died (n = 2) during cytoreductive second-line treatment (considered "cytoreduction failure"); none received ASCT, and their median second-line OS was <1 year. A total of 113 patients had POD24 (70%), whereas 49 had POD after 24 months (30%). Sixty-three patients without cytoreduction failure received ASCT (39%), and 81 received no transplant (50%). In patients with POD24, a significant survival benefit was associated with ASCT with a 5-year second-line progression-free survival for ASCT versus no transplant of 51% versus 19% (hazard ratio, .38; 95% confidence interval, .24 to .62; P < .0001) and a 5-year second-line OS of 77% versus 59% (hazard ratio, .54, 95% confidence interval, .30 to .95; P= .031). Thus, ASCT is an effective treatment option for transplant-eligible patients with high-risk FL as identified by POD24 and should be evaluated in prospective clinical trials.

Late mortality after autologous blood or marrow transplantation in childhood: a Blood or Marrow Transplant Survivor Study-2 report.

Autologous blood or marrow transplantation (BMT) is a curative option for several types of childhood cancer. However, there is little information regarding the risk of late mortality. We examined all-cause mortality, relapse-related mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US transplant centers. Vital status information was collected using medical records, National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. Cumulative incidence of mortality used competing risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-, and calendar-specific mortality rates from Centers for Disease Control and Prevention. Cox regression analysis was used to determine predictors of all-cause late mortality. Among the 345 2-year survivors, 103 deaths were observed, yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of death included primary disease (50.0%), subsequent neoplasm (21.4%), and infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population. Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI, 9.9-37.2) but approached those of the general population ≥15 years post-BMT. The 10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10-year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999, 25.6%; 2000-2010, 21.8%; P = .05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared with the general population. The late mortality rates have declined over the past 3 decades.

Heart Rate Variability Markers as Correlates of Survival in Recipients of Hematopoietic Cell Transplantation

OBJECTIVES: To assess pre-/post-transplantation changes in autonomic tone, as measured by heart rate variability (HRV), among patients undergoing hematopoietic cell transplantation (HCT) and to look at those changes as they relate to post-transplantation survival rates. 
. SAMPLE & SETTING: Data were derived from a sample of 27 English-speaking patients undergoing allogeneic or autologous HCT at Stanford University. 
. METHODS & VARIABLES: A survival analysis using the Kaplan-Meier estimator was employed to explore whether increased HRV would enhance survival probabilities over time among patients undergoing HCT.
. RESULTS: An increased probability of survival was significantly related to increases in two HRV indexes. IMPLICATIONS FOR NURSING: HRV may be a useful predictor of mortality among patients undergoing HCT. Interventions deliverable by nurses could be used to enhance HRV for patients identified as being at risk for early mortality.

Long-Term Clinical Outcomes Survey of Bone Marrow-Derived Cell Therapy in Critical Limb Ischemia in Japan.

BACKGROUND: The Therapeutic Angiogenesis by Cell Transplantation (TACT) trial demonstrated the efficacy and safety of autologous bone marrow-derived mononuclear cells (BM-MNCs) in patients with critical limb ischemia (CLI). The present study aimed to assess the long-term clinical outcomes of therapeutic angiogenesis using autologous BM-MNC implantation under advanced medical treatment in Japan.Methods and Results:The study was retrospective, observational, and non-controlled. We assessed no-option CLI patients who had BM-MNC implantation performed in 10 institutes. Overall survival (OS), major amputation-free (MAF), and amputation-free survival (AFS) rates were primary endpoints of this study. The median follow-up duration was 31.7 months. The 10-year OS rate was 46.6% in patients with arteriosclerosis obliterans (ASO) (n=168), 90.5% in patients with thromboangiitis obliterans (TAO) (n=108), and 67.6% in patients with collagen disease-associated vasculitis (CDV) (n=69). The 10-year MAF rate was 70.1%, 87.9%, and 90.9%, respectively. The 10-year AFS rate was 37.8%, 80.9%, and 61.2%, respectively. Major adverse cardiovascular events occurred in 6.0% of patients with ASO, 1.9% of patients with TAO, and no patients with CDV. CONCLUSIONS: Therapeutic angiogenesis using autologous BM-MNC implantation may be feasible and safe in patients with no-option CLI, particularly those with CLI caused by TAO or CDV.

Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplantation in POEMS Syndrome: A Nationwide Survey in Japan.

POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, vascular endothelial growth factor elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not been systematically studied. To clarify the efficacy and long-term outcomes of ASCT-treated patients in Japan, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation Transplant Registry Unified Management Program (TRUMP) database. Between January 2000 and December 2011, 95 patients (58 men) were registered to the TRUMP database with a median age of 53 years (range, 28 to 72). The conditioning regimen was melphalan in 93 of 94 patients (99%), and 69 patients (74.2%) received a melphalan dose ≥ 200 mg/m2. The median CD34 cell dose was 2.47 × 106/kg (range, .31 to 20). After ASCT, patient performance status was dramatically improved (Eastern Cooperative Oncology Group performance status 0 to 1: 20.0% versus 71.6%, P < .0001). Over a median follow-up of 46.6 months 10 patients died, and 5-year overall survival was 88.8% (n = 95). Progression-free survival at 3 years was 78.3% (n = 70; median follow-up, 54.4 months). These data support the promising role of ASCT in patients with POEMS syndrome for both prolonging survival and improving quality of life. However, disease recurrence remains a major issue for long-term survivors.

Plerixafor Plus Granulocyte Colony-Stimulating Factor for Patients with Non-Hodgkin Lymphoma and Multiple Myeloma: Long-Term Follow-Up Report.

The purpose of this report is to analyze long-term clinical outcomes of patients exposed to plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin lymphoma (NHL; n = 167) and multiple myeloma (MM; n = 163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240 µg/kg plerixafor plus 10 µg/kg G-CSF, or placebo plus 10 µg/kg G-CSF to mobilize and collect CD34+ cells for autologous hematopoietic stem cell transplantation. Overall survival (OS) and progression-free survival (PFS) were evaluated over a 5-year period following the first dose of plerixafor or placebo. The probability of OS was not significantly different in patients with NHL or MM treated with plerixafor or placebo (NHL: 64%; 95% confidence interval [CI], 56% to 71% versus 56%; 95% CI, 44% to 67%, respectively; MM: 64%; 95% CI, 54% to 72% versus 64%; 95% CI, 53% to 73%, respectively). In addition, there was no statistically significant difference in the probability of PFS over 5 years between treatment groups in patients with NHL (50%; 95% CI, 44% to 67% for plerixafor versus 43%; 95% CI, 31% to 54% for placebo) or those with MM (17%; 95% CI, 10% to 24% for plerixafor versus 30%; 95% CI, 21% to 40% for placebo). In this long-term follow-up study, the addition of plerixafor to G-CSF for stem cell mobilization did not affect 5-year survival in patients with NHL or patients with MM.

Clinical benefits of autologous haematopoietic stem cell transplantation in type 1 diabetes patients.

Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet function through immunological attack; therefore, it is also called 'insulin-dependent diabetes'. The present study aimed to evaluate the safety and clinical efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel-assignment, non-randomized trial was conducted from March 2008 to December 2011 with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only with insulin injections. Of these patients, 14 (70%) in the AHSCT group became insulin-independent for 1.5 to 48 months compared with only one patient in the Insulin group. Of these 14 AHSCT patients, 11 relapsed within a median time of 19.5 (range 5.5-1) months and resumed insulin use. By the end of the 4-year follow-up, the difference in daily insulin dosages between the AHSCT and Insulin groups had become smaller (0.49±0.32IU/kg/day vs. 0.79±0.18IU/kg/day, respectively; P<0.01). C-peptide levels increased significantly at 3 months in both groups and later decreased, with the insulin group showing more rapid deterioration. Most of the adverse events in the AHSCT group were transplantation complications. Our data suggest that AHSCT treatment was well tolerated and slowed deterioration of islet ß-cell function while significantly decreasing daily insulin dosages. However, because of the high relapse rate, more information on longer-term outcomes is needed before AHSCT can be routinely considered for T1D patients. SIGNIFICANCE: although this was a non-randomized clinical study, this phase-II trial demonstrated the beneficial effects of AHSCT in patients with newly diagnosed T1D by increasing C-peptide levels and inducing insulin independence, while showing its safety and good tolerability compared with conventional intensive insulin therapy. Thus, these results are helpful for increasing our understanding of the use of haematopoietic stem cell therapy in the treatment of T1D and for evaluating whether it can become more widespread in future.

Mid-term Outcome of 100 Consecutive Ross Procedures: Excellent Survival, But Yet to Be a Cure.

The Ross procedure offers excellent short-term outcome but the long-term durability is under debate. Reinterventions and follow-up of 100 consecutive patients undergoing Ross Procedure at our centre (1993-2011) were analysed. Follow-up was available for 96 patients (97%) with a median duration of 5.3 (0.1-17.1) years. Median age of the patient cohort was 15.2 (0.04-58.4) years with 76 males. 93% had underlying congenital aortic stenosis. Root replacement technique was applied in all. The most common valved conduits used for reconstruction of the right ventricular outflow tract were homografts (66 patients) and bovine jugular vein (ContegraR) graft (31 patients). Additional procedures included Ross-Konno procedure (14%), resection of subaortic stenosis/myectomy (11%) and reduction plasty of the ascending aorta (25%). One patient died within the first 30 days (1%). Late deaths occurred in 4 patients (4%) 0.5-4.5 years postoperatively: causes included pulmonary hypertension due to endocardial fibroelastosis (2), subarachnoid haemorrhage (1) and sudden cardiac death (1). Five-year survival was 93.6 (95% CI 88.1-99.1)%. Moderate or severe aortic (autograft) regurgitation needing reoperation occurred in 8 patients with a 5-year freedom from autograft reoperation of 98.5 (95.6-100)%. Five-year freedom from reintervention (surgery or catheter based) on the right ventricular outflow tract conduit was 91.5 (85.5-96.5)%. Univariate predictors of this reinterventions were smaller graft size (p = 0.03) and use of a ContegraR graft (p = 0.04). Ross procedure can be performed with low mortality and good survival in the long term. Most of the reinterventions are related to the neo-right ventricular outflow tract and may be partly attributed to the lack of growth. While the Ross Procedure remains an invaluable option for aortic valve disease in children, new solutions for the neo-pulmonary valve as well as for the less often occurring problems on the autograft are needed.