Hematopoietic Stem Cell Transplantation Program Research Articles

Identification, categorization, and mapping of indicators used by JACIE-accredited stem cell transplantation programs to assess distribution and coverage of processes.

255 Background: More than 145 European hematopoietic stem cell transplantation (HSCT) programs received JACIE accreditation since 2000, demonstrating compliance with FACT-JACIE international standards. The association of JACIE with improved patient outcome was recently documented. Conditions in which quality management systems were introduced and actual benefits remain to be fully evaluated. Methods: The study explores one aspect of quality management: introduction and use of indicators. Through a questionnaire sent to JACIE accredited centers, we aimed at identifying indicators (name, domain of application, category, longevity, and general description), understanding how they were set in place, whether or not similar indicators were used by different programs, and whether all of the HSCT processes were monitored. The survey was first sent to 14 French accredited HSCT centers and next to 68 other programs in 11 European countries. Categorization was double-checked against published criteria. Results: The response rate was 40% (32 programs). 293 indicators were collected, including 224 (76%) that were introduced during the preparatory phase of JACIE accreditation. Indicators were associated with the following processes measurement, analysis and improvement (54/293 or 18%); donor collection (49/293 or 16%); processing and storage of cell therapy products (37 /293 or 12.5%), administration of HPC (67/293 or 23%). Mapping reveals an uneven distribution of indicators across the different sub-processes that contribute to this highly-specialized medical procedure. Moreover, we found that only 101/293 indicators (34%) comply with the rules for implementation of a quality indicator, as defined by the FDX 50-171 standard. Conclusions: This suggests that risks to donors/recipients are unevenly monitored, leaving critical medical steps with low levels of monitoring.

Surgical Mask Usage Reduces the Incidence of Parainfluenza Virus 3 in Recipients of Stem Cell Transplantation

Abstract 462Respiratory viral infections (RVI) are frequent complications of hematopoietic stem cell transplantation (HSCT). Parainfluenza virus 3 (PIV3) in particular affects patients after HSCT, spreads nosocomially, and is associated with increased morbidity and mortality. Given the absence of proven effective treatments, prevention is key. However, surveillance and isolation of infected patients have been insufficient, likely foiled by asymptomatic viral shedding. Requiring all individuals with direct patient contact to wear a surgical mask is a simple and inexpensive intervention that may reduce droplet exposure by asymptomatic shedders and limit nosocomial spread.Prompted by recurrent clusters of PIV3 affecting our adult HSCT program, we performed an institutional review board approved prospective observational study to assess the impact of surgical mask usage. Between January 10, 2010-January 9, 2012 (mask period), all individuals with direct patient contact, including caregivers, visitors, and medical staff, were required to wear a surgical mask when within 3 feet of a patient, regardless of suspicion of RVI. This continued until the patient returned to their primary residence following completion of HSCT. The primary endpoint was the incidence of RVI compared to the control period of December 1, 2003-November 30, 2009 (pre-mask period). A brief washout period (December 1, 2009-January 9, 2010) allowed for training and implementation. Standard infection prevention precautions including strict hand washing were in place during both the pre-mask and mask periods. RVI (influenza A and B, PIV 1, 2, and 3, adenovirus, and respiratory syncytial virus (RSV)) were documented by positive culture, polymerase chain reaction, or direct fluorescence antibody testing from respiratory specimens. Metapneumovirus was excluded as our lab only started testing for it February 2011. Secondary endpoints include clusters of RVI, defined as 3 or more infections in a 30-day period, and death from RVI. The study was designed to detect a 40% reduction in the incidence of RVI with 90% power.During the six-year pre-mask period, 920 patients received HSCTs. During the two-year mask period, 454 patients received HSCTs. In the pre-mask and mask groups, mean age was 50 and 54 (t-test p<0.0001) (ranges 19 to 79 and 19 to 81). With the exception of non-Hodgkin lymphoma (21% and 15%) and plasma cell dyscrasia (32% and 46%) (chi-square p=0.004), there were no differences in disease representation among the two cohorts. Allogeneic HSCT constituted 41% and 33% of transplants (two-sided Fisher’s Exact Test p=0.004), of which 52% and 59% were myeloablative (p=0.18); 19% and 21% used cord blood as a donor source (p=0.63); 16% and 8% used a haploidentical donor (p=0.02); and 43% and 35% used alemtuzumab (p=0.12).The incidence of any RVI was 10.3% in the pre-mask period and 3.3% in the mask period (one-sided Fisher’s Exact Test p<0.0001) (Table 1). Among patients who had an allogeneic HSCT, the incidence was 16.9% and 6.7% (p=0.002); among patients who had an autologous HSCT, the incidence was 5.7% and 1.6% (p=0.005). Surgical mask usage had the most pronounced affect on reducing the incidence of PIV3 (8.2% to 2.0%, p<0.0001), which was the most common virus (74% and 60% of infections), followed by RSV (16% and 13%). There were more clusters in the pre-mask period (1.7/year vs. 0.5/year). In a blinded audit by three physicians (ADS, JAMS, MEH), viral infection contributed to patient death in 1.2% of patients in the pre-mask period and 0.2% in the mask period (p=0.12). Patients with RVI required more peri-transplant care (median 76 days vs. 21 days, Wilcoxon Rank Sum p<0.0001). These data suggest that requiring all individuals with direct patient contact to wear a surgical mask can reduce the incidence of RVI, particularly PIV3, during the most vulnerable period following autologous or allogeneic stem cell transplantation.Table 1Incidence of Viral InfectionsVirus % (n)Pre-Mask (n = 920)Post-Mask (n = 454)p-valueAny10.3% (95)3.3% (15)<0.0001Influenza A0.5% (5)0.4% (2)1.0*Influenza B0.1% (1)0% (0)1.0*Parainfluenza 10.1% (1)0% (0)1.0*Parainfluenza 20.3% (3)0% (0)1.0*Parainfluenza 38.2% (75)2.0% (9)<0.0001*Adenovirus0% (0)0.4% (2)1.0*Respiratory Syncytial Virus1.7% (16)0.4% (2)0.24**One-sided Fisher's Exact Test adjusted for multiple comparisons using the Bonferroni approach. Disclosures:No relevant conflicts of interest to declare.

The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program.

123-P

Aim A hematopoietic stem cell transplantation program in Santiago, Chile affiliated with St. Jude Children’s Research Hospital referred 190 patients and their family members for HLA typing between 2000 and 2011. Methods These individuals were studied for HLA specificities by the use of sequence-specific oligonucleotide primers (SSP), sequence-specific oligonucleotide probes (SSO) and DNA sequencing. Haplotype assignment could be made unambiguously in all cases from family studies. Results The expectation of the referring center was that this group consisted largely of those of western European origin. HLA typing of the large proportion of this referred group indicated that although 70 - 80 % was similar to populations found in western Europe, a substantial number demonstrated alleles not found in western Europeans and which were initially described in native South American populations. For example, of 35 patient samples positive for HLA-A ∗ 68, 34 (97%) were found to be HLA-A ∗ 68:01:02 by DNA sequencing, a variation described in native South American populations. HLA-A ∗ 68:23 was identified in 8 unrelated individuals in this group of 719 patients and family members. This would indicate that this unusual allele would meet the criteria for a common and well-documented allele in this population. Alleles of HLA-A ∗ 02, A ∗ 24, as well as other A ∗ 68 alleles not commonly seen in those of western European heritage were also found. Eleven HLA-B ∗ 35, six HLA-B ∗ 39 and five HLA-B ∗ 51 alleles first described in native South American populations were also found in HLA typing of this group from Chile. HLA-DRB1 ∗ 04:07 was shown in 87 and HLA-DRB1 ∗ 08:02 in 55 of these 719 individuals. Conclusions Unrelated donor registries in Argentina and Brazil have recently formed cooperative agreements with the National Marrow Donor Program and can be expected to be beneficial for those patients from South America requiring unrelated hematopoietic stem cell donors.

Heterogeneity of HLA‐DRB1*04 alleles and haplotypes in the Croatian population

Analysis of allele distribution at the HLA-DRB1*04 gene, as one of the frequent ones among Croatians, and their HLA-A-B-DRB1 haplotypes in the Croatian population was performed in this study. Using LABType® SSO and PCR-SSP method, 11 DRB1*04 subtypes were observed, of which DRB1*04:01 was the most frequent (28.0%) followed by DRB1*04:02 (26.3%), DRB1*04:03 (22.3%), and DRB1*04:04 (14.2%). The significant haplotypes (with highest P value) for given DRB1*04 allele were the following combinations: HLA-B*15:01-DRB1*04:01, HLA-B*38:01-DRB1*04:02, HLA-B*35:03-DRB1*04:03, HLA-B*35:03-DRB1*04:08, HLA-B*14:01-DRB1*04:04, and HLA-B*49-DRB1*04:05. Marked differences in the distribution of our most frequent haplotypes of HLA-B-DRB1*04 (HLA-B*38:01-DRB1*04:02 and HLA-B*15:01-DRB1*04:01) were found in comparison to other European populations investigated so far. Additionally, comparison of HLA-A-B-DRB1*04 haplotypes showed that although there are similarities in the haplotype structure between our and other populations, there are also noteworthy differences. In summary, the identification of conserved and unusual DRB1*04 haplotypes in the present study of Croats should have important clinical implications for donor-recipient matching in the hematopoietic stem cell transplantation program, help in the understanding of HLA polymorphisms in different European populations, and also prove to be very useful in the determination of possible susceptibility genes involved in HLA-DRB1*04-associated diseases.

City of hope cancer center hematology–oncology fellowship and hematopoietic stem cell transplantation fellowship

The City of Hope (COH) ACGME-accredited Hematology-Oncology fellowship began in 1978 with two fellows and has grown up to seven fellows per year. It remained as the last fellowship independent of an Internal Medicine Training Program until its affiliation with Harbor-UCLA Internal Medicine Program as the Research Track of the fellowship in 1995. City of Hope Cancer Center is an NCI-designated comprehensive cancer center, a founding member of National Comprehensive Cancer Network, and one of the top medical centers as named by the US News and World Report. This provides an ideal environment for learning patient care and research within both a county hospital and a tertiary teaching hospital setting. In addition, it provides ample opportunities for both basic science and clinical research in the latter years of the fellowship. The fellowship is a fully-funded 3-year program which provides experience through a multidisciplinary approach to prepare trainees for a successful career in academic medicine or private practice.

JACIE fête son dixième anniversaire

JACIE (Joint accreditation committee for ISCT Europe and EBMT) is a comprehensive quality management system built in under the auspices of two European professional societies. The singularity of JACIE is its coverage of all the main actors - clinical wards as well as collection and processing facilities - that contribute to a hematopoietic stem cell transplantation program. Deployment of JACIE started ten years ago. A recent retrospective analysis of the large-size european registry of autologous and allogenic hematopoietic stem cell transplantations demonstrates that one of the factors affecting the overall survival of recipients of allogenic transplantation is the status of the transplant program regarding JACIE accreditation. This provides one of the first demonstrations that introduction of a quality management system can contribute to the overall survival of patients treated with a highly specific and complex medical procedure.

Trasplante de Progenitores Hematopoyéticos en Pediatría: 10 Años de Experiencia

ABSTRACT Hematopoietic Stem Cell Transplantation in Pediatrics: 10 years experience Background: In Uruguay the survival estimates for pediatric patients with cancer are comparable to those in developed countries. With the aim of improving outcomes in patients with worse prognosis and provide therapeutic options for treating some non malignant diseases, we started a hematopoietic stem cell transplan-tation (HSCT) program in 1997, with the fi nancial support of the National Resources Fund (Fondo Nacional de Recursos-FNR). Patients and Methods: The unit was created at the Asociacion Espanola Hospital and counts with three rooms with a sophisticated isolation system. Isolation measures and guidelines for preven-ting opportunistic infections were strictly enforced. HSCT indications followed the national FNR guidelines according to recommendations of international groups. International standards were used for the patients ma-nagement. Results: In 10 years 131 transplants were performed in 129 patients. The 10 year overall survival estimate was 43.9 ± 4.6%. Transplant related mortality was 9.3% and the main cause of death was infections. In allogenic HSCT acute graft

Preparing for Growth: Current Capacity and Challenges in Hematopoietic Stem Cell Transplantation Programs

During the past decade, the demand for hematopoietic stem cell transplantation has grown dramatically, and there are expectations that this will continue or even accelerate over the next decade. This prompts a variety of questions about the ability of the health care system to accommodate the increased demands on transplantation centers; for example, what is the current patient capacity of transplantation programs, and how much elasticity do they have to accept a larger volume of patients? An informal survey of a sample of medical directors of transplantation programs found that existing facilities might be able to increase their patient volume by about 7%. Expanding much beyond that limit will require an infusion of resources to enlarge current programs and/or establish new programs.

Status of hematopoietic stem cell transplantation in the WHO Eastern Mediterranean Region (EMRO)

Several centers are now performing allogeneic hematopoietic stem cell transplantation (HSCT) in the World Health Organization Eastern Mediterranean Region (EMRO) but the availability is still limited due to high cost and the need for multi-disciplinary team and an advanced laboratory support. Special issues including compatible donor availability, potential for alternate donor programs, differences in pattern of disease, pre-HSCT general status particularly for patients with BM failure, high sero-positivity for CMV, Hepatitis B and C infection and specific observations about GVHD with its relation to genetically homogeneous community are discussed. A total of 17 HSCT programs (performing five or more HSCTs annually) exist in nine countries of the EM region. Only six programs are currently reporting to EBMT or IBMTR. A total of 7617 HSCTs including 5701 allogeneic HSCTs have been performed. Due to low HSCT team density (1.5583 teams/10 million inhabitants versus 14.4333 in Europe) and very low HSCT team distribution (0.2729 teams/10,000 sq km area versus <1 to 6 teams in Europe) only 70.8% of total population has access to such a program in EM region. GNI/capita had no clear association with low HSCT activity; however improvement in infrastructure and establishment of EM regional HSCT registry need prioritization.

The Experience of Hematopoietic Stem Cell Transplantation From An Emerging Centre in North India.

Abstract 4317 IntroductionWith a huge burden of hematological and oncological disorders for which hematopoietic stem cell transplant (HSCT) is a curative option, India saw the development of HSCT program from 1986 onwards. Since then, some 10 centres have performed over 1600 transplants until the year 2005, including one-third in thalassemic patients. However, current HSCT facilities are still limited and cannot address the treatment needs of the immense patient load. There is a need for new transplant centres in India. We are describing our experience of HSCT programme at Sir Ganga Ram Hospital, a tertiary hospital in North India, over a period of 3 years. Patients and methodsA retrospective study of all patients who underwent HSCT over a period of 3 years, from January 2006 to August 2009 was done and follow-up data was analyzed. ResultsThirty-nine transplants (16 allogenic and 23 autologous) were done during this period in 34 patients (26 males and 8 females). The median age of transplant patients was 34 years (11 months-68 years). Children comprised 41.2% of the patients. The indications for 16 allogenic transplants were thalassemia major-6, acute myeloid leukemia (AML)/myelodysplastic syndrome-6, severe aplastic anemia-3 and high-risk acute lymphoblastic leukemia-1. Donors were HLA-matched sibling in 13 cases, HLA-matched relative in 1 and unrelated umbilical cord blood in 2. The source of HSCT was peripheral blood in 8 patients, bone marrow in 6 and umbilical cord blood in 2. Fourteen patients underwent myeloablative transplants and two were given reduced intensity conditioning. Three Donor Lymphocyte infusions were given to two patients. Seven patients (44.8%) are alive and disease free at a median follow-up of 453 days (65-591 days). Thirteen patients showed neutrophil engraftment at a median duration of 14 days (range 11 to 44). Engraftment syndrome was seen after unrelated cord blood transplant in one child. Acute Graft versus host disease (GVHD) was seen in 6 patients, grade I-II was seen in 5 patients, which responded to steroids. Steroid-refractory grade IV GVHD was seen in one child; it did not respond to mycophenolate and infliximab. Massive bleeding (gastro-intestinal-2 and pulmonary-1) occurred in three children. Three patients developed sinusoidal obstruction syndrome. All were given Defibrotide and two responded. A total of 7 allogenic HSCT recipients have died, out of which 2 AML patients died of relapse at 56 and 90 days post-transplant. The main causes of death in 5 other patients were sepsis (3 bacterial and 2 fungal), sinusoidal obstruction syndrome (1 case), acute GVHD (1 case) and chronic GVHD (1 case). Two thalassemic children rejected graft but are alive and transfusion dependent. The main indications for 19 autologous HSCT were multiple myeloma-9, Non-Hodgkin's lymphoma-4, metastatic neuroblastoma-2, relapsed Hodgkin's lymphoma-1, relapsed rhabdomyosarcoma-1, relapsed primitive neuroectodermal tumor (PNET) of the kidney-1 and rejection post cord blood transplant in thalassemia-1. The source of HSCT was peripheral blood in 16 patients and bone marrow in 3. Ten patients (55.6%) are alive and disease-free at a median follow up of 114 days (range 21 - 617 days). Seventeen patients engrafted neutrophils at a median duration of 12 days (range 9 to 30). A child with metastatic neuroblastoma relapsed 8 months post transplant and is on palliative radiotherapy. An adult with indolent lymphoma relapsed 1-year post transplant and is in partial remission two years after relapse. Six autologous HSCT recipients have died. One adult with NHL died of progressive disease one-month post transplant and one with multiple myeloma died of relapse 3-years post transplant. One child with PNET received 4 autologous staged transplants and local radiotherapy with very good partial response but died of candida sepsis 92 days after his last transplant. Three other patients died of bacterial sepsis. At a median follow up of 200 days (range 21 to 1200 days), the estimated overall survival and event free survival for all the transplant population are 67.3% ± 8.6% and 63.5± 8.9% respectively. Overall transplant related mortality is 23.5%, with a decrease from 28.6% to 22.2% after a dedicated HSCT unit with HEPA filtered rooms became functional by mid 2007. ConclusionWith our encouraging results we can conclude that it is possible to setup a HSCT unit in developing world and results get better with each passing year. Disclosures:No relevant conflicts of interest to declare.

Innovative Supportive Care Practices for Stem Cell Transplantation in India

Hematopoietic stem cell transplantation (HSCT) may be considered as an inappropriate technology in a developing country because of the high cost of the procedure for an individual patient [1]. To make this modality available to a larger population as a life-saving treatment, innovations and modifications are required to reduce the cost without compromising the outcomes. This article describes our attempts to develop a cost-effective HSCT program in India [2].

Results of Alternative Donor Search in Adult Patients with Severe Sickle Cell Disease (SCD) Eligible for Hematopoietic Stem Cell Transplantation (HSCT).

Supportive care has improved the outlook for patients with SCD, but life expectancy remains considerably shorter than those without SCD. The major causes of mortality are end-organ failure, stroke, pulmonary disease, and acute vaso-occlusive crises (VOC). Myeloablative allogeneic HSCT in children under age 16 is curative in the majority. However organ damage that meets severity criteria for HSCT may not become evident until adulthood, at which time conventional myeloablative transplant is no longer an option. Additionally, the great majority of SCD patients do not have a 6/6 HLA-matched sibling donor available. Reduced-intensity conditioning may extend this potentially curative treatment to adults with SCD. Since non-myeloablative transplants may result in mixed donor chimerism, major ABO-mismatch may lead to red cell aplasia, and therefore should be avoided. Finally, cell dose is likely an important parameter in non-myeloablative transplant regimens, potentially further limiting donor availability. We initiated an IRB approved non-myeloablative allogeneic HSCT program for adults with severe SCD for whom a matched sibling donor is available. For those without related donors, we devised a search strategy for alternative donors to establish the feasibility of matched unrelated donor (MUD) or umbilical cord blood (UCB) HSCT. HLA typing was performed for potential donors and patients who on initial screen met at least one the following criteria: stroke, pulmonary hypertension, sickle related nephropathy, or frequent VOC/ACS not improved by HU. Typing at the serologic level was performed for HLA-A,-B, and at the allele level for HLA-DR B1. For patients without matched sibling donors, searches in the National Marrow Donor Program for marrow and cord blood donors were initiated. Since 2003, we performed initial screening in >100 patients, typed 58 potential recipients and 85 donors, and identified 13 potential recipients (age ≥ 16 years) with matched sibling donors. Two were excluded because of major ABO incompatibility. Among the remaining 43, 10 patients who met all study criteria on full screening were selected for alternative donor searching. MUD search results identified a median of 2.5 (range 0–18) 6/6 HLA-matched donor available. Five individuals had 0, four had 4–6, and one had >15 potential donors. UCB search revealed no patient had a 6/6 HLA-matched, two had 15–16 5/6 HLA-matched, and five had 11–190 4/6 potential donor UCB units. The median UCB units containing ≥ 2 × 10e7 nucleated cells per kg were 0 for 6/6 HLA-matched (range 0–1), 0 for 5/6 HLA-matched (range 0–19), and 8.5 for 4/6 HLA-matched (range 0–190). When ethnic haplotype and allelic frequency, the available ABO status, the likelihood of requiring two UCB units for each adult recipient were considered, 5 had neither MUD nor UCB units available, 2 only had potential UCB units available, and 3 had both MUD and UCB units available. The majority of adults with severe SCD who are eligible for non-ablative allo-HSCT do not have matched sibling donors. Our search shows that the minority of African-American adults have potential alternative donors, 10% and 50% MUD and UCB, respectively. These numbers will likely be reduced when major ABO mismatches are excluded. Further, unlike pediatric patients, one cord blood unit may not provide sufficient cells to overcome the barrier of graft rejection in most adults. Given these limitations, the feasibility of haplo-identical family donor allo-HSCT should be investigated.

Stem cell transplantation in Multiple Sclerosis: Safety and Ethics

Stem cell therapy is considered a promising strategy aiming at neuronal and glial cell replacement or neuroprotection in neurological diseases affecting the brain and spinal cord. Multiple Sclerosis (MS), characterized by inflammation-induced destruction of the myelin sheath surrounding axons leading to conduction deficits and variability of clinical signs, is not an exception. MS is considered an autoimmune disease and, in the last few years, an intense immunodepletion followed by autologous hematopoietic-stem-cell transplant (HSCT) is being assessed as potential therapeutical strategy for severe patients unresponsive to the immunomodulatory and immunosuppressive treatment. Partially supported by evidence in animal models and by anecdotal reports on the beneficial effects on MS patients with concomitant malignant diseases, HSCT programs for MS have been initiated worldwide and follow-up data are accumulating. A Consensus Meeting has been held in Milano (1998) providing a document that defined criteria for patient selection, transplantation procedures, and outcome evaluations. Nowadays the high number of patients already treated allows us to draw initial conclusions related to clinical efficacy. After careful monitoring of the available data and improvement of the procedure, safety seems not to be anymore an issue. Ethics of HSCT deserve, on the contrary, a profound evaluation: the procedure is a multistep process with manifold options, each step with different ethical implications. Even more difficult appears the definition of the MS patient selection criteria for HSCT. The informed consensus needs to be exhaustive for the full comprehension of a complex procedure. In conclusion, although HCST is today an established therapeutical option for MS patients, safety and ethical issues need to be further clarified.

Patterns of use of vascular access devices in patients undergoing hematopoietic stem cell transplantation: results of an international survey

There is limited information regarding of use of vascular access devices (VAD) in patients undergoing hematopoietic stem cell transplantation (HSCT). The frequent use of VAD in HSCT and its potential to cause morbidity requires understanding of the general use of VAD in HSCT. A World Wide Web-based 19-item questionnaire was designed to determine the patterns of use of VAD in patients undergoing HSCT. The questionnaire was sent via electronic mail to the directors of HSCT programs throughout the world. Of the 445 centers surveyed, 163 centers replied for a response rate of 37%. The most commonly used catheter for autologous peripheral blood stem cell (PBSC) harvest is the dual-lumen plasmapheresis/hemodialysis (62%). Of the institutions, 58% utilize the same catheter used for PBSC harvest to provide vascular access support during the transplant. Catheter-related blood stream infection (36%) and withdrawal occlusion (31%) were the most frequently encountered complications of VAD. Of the centers, 65% have established criteria for VAD removal when infection is suspected and 48% when occlusion is suspected. Our study demonstrated that there are similarities in the utilization of VAD but also wide differences in the standard procedures for the insertion and care of VAD in the transplant setting. More comprehensive studies are needed to assess the use of central venous catheters in transplant recipients. Important areas for future research include the impact of VAD utilization on the quality of life of transplant recipients and the final consequences of VAD complications.

Adult Mismatched Umbilical Cord Blood Transplant Is Feasible in a Community Setting for an Unselected Group of High Risk Patients.

Conflicting results has been found on how the size of a transplant program affected the clinical outcome of hematopoietic stem cell transplant (HSCT). Some insurance carriers demand their clients to only receive HSCT in large centers, even if the service is available locally and the patients have to travel a long distance away from their home to receive the service at the approved program. Amarillo, Texas is 350 miles from Dallas and 600 miles from Houston. The HSCT program was established in Dec 2001. 18–25 transplants (autologous, allogeneic and umbilical cord blood (UCB) transplants) are performed a year. To determine whether a justification could be made to offer HSCT in a program that is small, new and community-based, we have analyzed the outcome of the adult mismatched umbilical cord blood transplants (UBCT) carried out on an unselected group of patients needing HSCT but without a matched sibling donor in our center in the last five years.Thirteen patients (8 males and 5 females) have undergone unrelated mismatched UBCT. The median age was high at 54 years (range 17 to 78). Four patients received reduced intensity conditioning regimen with Flu/Mel and 9 patients received the myelo-ablative regimen with Bu/Cy. Four patients received two units and nine single unit of umbilical cord blood. The diagnosis were: CML in CP1 (1), CML in blast crisis (2), HD relapsed within three months after autologous transplant (1), SAA (2), refractory CLL (1), ALL with multiple relapses (1), AML in CR3 (1), untreated secondary AML (2), primary refractory AML (1) and secondary AML in CR1 (1). Five patients received UCB units that were 1 antigen mismatch, 4 patients 2 antigen mismatches and 4 patients 3 antigen mismatches. GVHD prophylaxis in all cases consisted of cyclosporine A and methylprednisone.This is a group of mainly very high risk older patients. Not unexpectedly, early mortality rate was high. Death within 28 days of transplant occurred in 2 patients due to toxicity. Death within 100 days of transplant occurred in 8/13 (61.5%) patients. All the deaths occurred due to either infection or toxicity, except in one patient (age 67 years) who died due to a thrombotic stroke. Death due to disease relapse occurred in another patient 5 months after transplant for CML in blast crisis. Engraftment was documented in 9 patients. Despite the high antigen mismatches and the age of the patients, Grade I – II GVHD occurred in 7 patients and Grade III – IV in only 2 patients.With a maximum follow-up of 49 months, 4/13 (30%) patients are alive disease-free: 49+ months (age 45 years, one DRB1 mismatch), 22+ months (25 years, two antigen mismatches), 15+ months (48 years, three antigen mismatches) and 4+ months (54 years, three antigen mismatches). These results, in a group of very high risk unselected older patients in a community setting, are extremely encouraging and are comparable to those reported on younger groups of patients.Conclusions:Adult mismatched UBCT is feasible in a small program in a community setting;Patients >45 years may benefit from UBCT, even in the setting of multiple antigen mismatches;Patient selection should reduce early death and improve survival;Insurance companies should not deny patients to have transplant in their local program based on the size of the program.

The John Ultmann lecture – the role of radiation therapy in the treatment of Hodgkin's disease: past, present, and future

Radiation therapy has been used in the treatment of Hodgkin's disease for more than a century. At first it was demonstrated to provide significant palliation. As advances in technology permitted a more controlled delivery of radiation to defined regions, long lasting responses of disease were demonstrated. Beginning in the mid-1960s, Vera Peters and Henry Kaplan demonstrated the curative potential of high dose extended field irradiation in the treatment of stage I-II Hodgkin's disease. As effective programs of chemotherapy evolved, combined modality therapy with intensive chemotherapy and extensive radiation was applied for patients with early stage disease, resulting in significant morbidity and some mortality. More recently, combined modality programs of brief chemotherapy and limited radiation have been extremely successful in managing patients with stage I-II disease. In addition to its utility in early disease, radiation therapy is an integral component of treatment programs for patients with large mediastinal adenopathy. It has also proved useful in patients with stage III-IV who achieve only a partial response to chemotherapy and may also have a role to play as a component of high-dose therapy hematopoietic stem cell transplant programs. Radiation therapy remains the most effective single agent for the treatment of Hodgkin's disease.

Maintaining high autopsy rates in a Canadian blood and marrow transplant program: preserving a diagnostic and research tool

Autopsy series have revealed patterns of injury in graft-versus-host disease and provided insight into infectious and toxic complications following hematopoietic stem cell transplantation (HSCT). Overall autopsy rates have declined significantly in recent decades including specialized services such as neonatal medicine and cardiac care. However, rates of post-mortem exams at HSCT centers have not been specifically documented. We reviewed hospital records between 1992 and 2002 to determine overall autopsy rates at our hospital and within the HSCT program. Although the overall autopsy rate declined steadily from 24% in 1992 to 9% in 2002, rates of post-mortem exams in the HSCT program remained relatively stable at 32% (24-46%). Autopsy rates were not significantly different for recipients of allogeneic vs autologous transplants and no clear difference was observed for the proportion of autopsies requested on weekdays compared with weekends. Autopsies confirmed major clinical diagnoses and/or suspected causes of death in 45 of 61 autopsies (74%) and yielded major or minor disagreements in clinical diagnosis in 10 cases (16%) and seven cases (11%), respectively. The preservation of high rates of autopsy within our HSCT program demonstrates that specialized programs are able to maintain elevated rates of post-mortem examinations despite overall declining rates.

HLA made simple: Chromosomes, genes, and alleles, oh my

Patients who are candidates for allogeneic hematopoietic stem cell transplantation (HSCT) must be HLA typed to find the best donor. It is important for the nursing staff of a HSCT unit to understand HLA and how the recipient is matched to the donor. St. Jude has incorporated haploidentical donor transplantations into their HSCT program. Knowledge of the recipient and donor HLA match can be beneficial for the nursing regarding potential complications during tranpslant and issues revolving around engraftment.

Patterns of Use of Vascular Access Devices (VAD) in Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT): Results of an International Survey.

Background: There is limited information regarding the patterns of use of VAD in patients undergoing HSCT. With its frequent use in HSCT and its potential to cause morbidity, studying the patterns of VAD use have clinical and preventive implications.Methods: A World Wide Web based 19-item questionnaire was designed to determine the patterns of use of VAD in patients undergoing HSCT. The questionnaire was sent via electronic mail to the directors of HSCT programs throughout the world.Results: Of the 445 centers surveyed, 163 centers replied for a response rate of 37%. Fifty-seven percent of the respondents were from North America, 21% from Europe, 7% from Asia and 15% from other geographic areas. Sixty-two percent of the institutions were university-based or teaching institutions and 18% were primarily cancer center-based. In 26% of the institutions VAD are inserted by interventional radiologists and in 18% by general surgeons. The remaining institutions utilize several healthcare professionals for VAD insertion including physicians, physician assistants, and nurses. Sixty-two percent of centers use the subclavian vein as the preferred site of insertion while 31% prefer to use the internal jugular vein. VAD insertions are done in the operating room in 36% of centers, while 26% of the institutions prefer to use the radiology suite. The majority of the institutions (82%) did not give prophylactic antibiotics to patients before VAD insertion. The most commonly used method to determine catheter position was chest X-ray (62%) followed by fluoroscopy (36%). The most frequently utilized VAD for autologous peripheral blood stem cell (PBSC) harvest when peripheral vein access was not possible was the two-lumen silicone pheresis type catheter (62%). Fifty-eight percent of the institutions utilize the same catheter used for PBSC harvest to provide vascular access support during the transplant. The most frequently utilized VAD for allogeneic stem cell transplantation was the multilumen silicone pheresis type catheter (68%). Only 18% utilize low-dose warfarin routinely for prophylaxis of VAD-related thrombosis. When thrombosis of the catheter is suspected, 82% of the transplant centers routinely perform radiologic studies. The most common radiologic study performed to evaluate VAD thrombosis was sonography (63%) followed by venography (25%). Medications utilized by the institutions for initial therapy of VAD occlusion included recombinant tissue plasminogen activator (48%), urokinase (23%) and heparin (18%). Of interest, 64% of the institutions had established criteria for removal of VAD when infection was suspected or documented and only 48% had established criteria for removal of VAD when occlusion was suspected or established. Sixty-nine percent of the institutions had established criteria for removal of VAD after transplantation.Conclusions: The patterns of use of VAD during HSCT vary widely across institutions. Many centers do not have established criteria for VAD removal after HSCT or in response to VAD complications. Studies should be performed to determine the optimal use of VAD during HSCT.