Hematopoeitic Stem Cell Transplantation Research Articles

Tear inflammatory mediators and protein in eyes of post allogenic hematopoeitic stem cell transplant patients

AimTo analyze tear cytokines levels and their correlation to ocular surface parameters in allogenic hematopoietic stem cell transplants (allo-HSCT) patients. MethodsProspective longitudinal study of allo-HSCT patients and controls for ocular surface evaluation (OSDI, TBUT, Schirmer's test, staining scores), tear biochemical analysis for protein, cytokines [IL-10, IL-12, IL-2, IL-4, IL-6, IL-17, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, VEGF], MMPs [MMP 2, 9, 7, 13, 10 and chemokine (IL-8)], & VEGF on three consecutive follow up visits (at three monthly interval) was done. ResultsOf 24 post allo-HSCT patients (19 males, 5 females) & 12 controls (mean age 34.3 + 5.8 years) enrolled, 20 patients [mean age 33.4 + 7.77 years; mean time of recruitment of 5.2 + 2.12 months following alloHSCT] who completed three consecutive follow up visits were included for analysis. Ocular GVHD (oGVHD) was seen in 8 patients (33.3%). Tears biochemical analysis showed elevated levels of interferon γ, IL 6, IL 8, IL 10, IL 12AP70, IL 17A, MMP 9 and VEGF in oGVHD eyes as compared to non-oGVHD & control eyes. Non-oGVHD eyes showed elevated tear MMP 7 and MMP 9 as compared to healthy controls. Tear protein levels were significantly decreased in oGVHD eyes and were equivocal in nonGVHD and control eyes. TBUT and ocular staining scores to correlate best with tear interleukins and MMPs. ConclusionEvaluation of levels of tear VEGF, total protein & MMP 9 can be of significance in identifying oGVHD in post alloHSCT patients.

P227 Determination of HLA -A, -B and - DRB1 alleles and HLA-A -B haplotype frequencies in Egyptians based on family study

Knowledge of allele and haplotype frequencies in human populations guides the search for an HLA- matched unrelated hematopoietic stem cell donor. A new algorithm developed by the National Marrow Donor program uses this information to predict the likelihood that a volunteer of a particular ethnicity will carry specific HLA alleles when typed at high resolution. In the present study, we determined the HLA-A,-B and -DRB1 alleles and HLA-A-B haplotype frequencies in Egyptians and compared them to various populations. Specificities of HLA-A, -B and -DRB1 loci were determined in 286 matched related donors of allogeneic hematopoeitic stem cell transplantation (AHSCT). Typing was performed using serologic and low resolution PCR- reverse sequence-specific oligonucleotide (rSSO) techniques. HLA-A-B haplotypes were defined by segregation analysis. The most frequent alleles for HLA class I HLA-A were: HLA-A2 (19.2%), A1 (15.8%), A30 (9.2%) and A24 (8.8%), for HLA-B, B41 (10.9%), B35 (10.2%), B44 (6%) and B50 (5.4%) and for DRB1∗13 (18.7%), ∗04 (15%) ,∗11(14.7%) and ∗03 (13.2%). The most frequent HLA-A-B haplotypes were: A24-B35 (3.8%), A2-B41 (3.4%), A1- B35 (3.4%) and A33-B14 (3.4%). This study report HLA allele and HLA-A-B haplotype patterns in Egyptians. These patterns were close to Jordanians and Lebanese and different from Saudi Arabians, Europeans, Americans and Asians. These data explain the difficulty of finding donors in world registries for Egyptian patients in need of a stem-cell transplant and highlight the need to for planning an Egyptian national unrelated donor registry to meet the demands of these patients.

High‐dose chemotherapy with autologus hematopoeitic stem cell transplantation in relapsing Vitreoretinal Lymphoma, a LOC network study

PurposeThe management of isolated vitreoretinal lymphoma (VRL) remains controversial due to his rarity. The aim of this study was to evaluate the efficiency and safety of high‐dose chemotherapy with autologous hematopoietic stem cell transplantation (HCT‐ASCT) as a treatment of recurrent relapsing VRL.MethodsWe retrospectively studied medical records of patients included in the French LOC network database between 2011 and 2016 with isolated vitreoretinal relapse of either primary vitreoretinal lymphoma or oculocerebral lymphoma treated with HCT‐ASCT. Hematologic, neurologic and ophtalmologic datas were screened.Results32 patients (16 F/16 M), all immunocompetent, were included in the study. Median age at HCT‐ASCT was 62 (range 44–73 years). Median Karnofsky Performance status before HCT‐ASCT was 90. At diagnosis, 17/32 had primary vitreoretinous lymphoma (PVRL), 7/32 Primary Central Nervous Cells Lymphoma (PCNCL), 8/32 PVRL and PCNL. Patients had previously received a median number of 1 line of treatment including high‐dose methotrexate before HCT‐ASCT. All patients received a thiotepa‐based HCT. 81% of the patients experienced a complete response. 2 “toxic deaths” occurred. Mean follow‐up was 41.6 months (range: 5–96). 9/32 patients had recurrences. The 5‐years OS was 81%. The 5‐years OS was respectively 91% in the PRVRL groups, 85% in ocular and cerebral group and 64% in PCNCL group. The 5‐years PFS rate was 58%. The 5‐years PFS was respectively 66% in the PRVRL groups, 75% in ocular and cerebral group and 43% in PCNCL group. 4 deaths occurred overall.ConclusionsIntensive chemotherapy followed by autologous stem cell transplant is an aggressive therapeutic approach but appears to give interesting results especially in young and fit patients with recurrent refractory vitreoretinal lymphoma.

Cytomegalovirus reactivation posthematopoietic stem cell transplantation (HSCT) and type of graft: A step toward rationalizing CMV testing and positively impacting the economics of HSCT in developing countries.

We aimed to determine a correlation between cytomegalovirus reactivation post hematopoeitic stem cell transplantation (post-HSCT) with the type of graft source, defining children at risk. We analyzed data on children less than 18 years of age undergoing HSCT from 2002 to May 2016 (n = 464). Correlation between reactivation and graft source was analyzed statistically. Reactivation occurred in 3% of children with matched-related donor (MRD) transplants, 33.3% with unrelated peripheral blood stem cells, 17.4% with unrelated cords, and 36.5% (15/41) with mismatched or haploidentical grafts (P = <0.0001). MRD does not warrant weekly PCR, unlike unrelated or haploidentical donors, thus defining protocols for developing countries with limited resources.

Hematopoeitic Stem Cell Transplant in Aplastic Anemia: Is It Time to Revise the Treatment Alogirthm

Background: Aplastic anemia (AA) is a rare bone marrow failure (BMF) syndrome of unknown etiology characterized by hypocellular bone marrow and severe persistent pancytopenia. Pediatric AA is more common in adolescent age group with better outcomes as compared to adults. Current treatment modalities include immunosuppressive therapy (IST) or matched related bone marrow transplant, when possible. There is a high risk of disease relapse with IST and clonal evolution into myelodysplastic syndrome. There is limited pediatric data on outcomes with different treatment options.Methods: Retrospective database analysis of Pediatric Health Information Systems (PHIS) database was performed to evaluate healthcare outcomes of pediatric patients (age less than 21 years) with AA from January 1, 2006 to December 31, 2015. PHIS is an administrative quality-controlled database from 43 not-for-profit children's hospitals. ICD-9 code 284.9 was used to identify patients with acquired AA. Appropriate procedure and pharmacy billing codes were used to obtain information regarding transplants and various drugs used. SAS based statistical software was used to perform analysis.Results: A total of 5127 inpatient admissions were noted for AA during the study period. An overall increasing trend of transplant was observed from 2006-2015 (Figure 1). Almost equal inpatient admission rate was noted in males and females, with a slightly higher rate amongst males who underwent transplant (55% vs 45%). Inpatient admission was more common amongst whites in both transplant (n=407, 8%) and non-transplant groups (n=4717, 92%; Table 1). Overall inpatient mortality was about 2% with a similar mortality in those who underwent transplant (5%). Cyclosporine (n= 1785, 38%) and steroids were most common immunosuppressive drugs used in non-transplant group. In the transplant group (Table 2), graft failure (20%) was the most common complication, while Cyclophosphamide (77%), Fludarabine (53%) and anti-thymocyte globulin (31%) based conditioning was most commonly used. Transplant itself was an independent risk factor for mortality (p=0.04) along with graft failure (p=0.02). Steroids (92%) and Cyclosporine (73%) were the most common immunosuppression used.Conclusion: Hematopoietic stem cell transplants have good outcomes in pediatric AA patients. With an increasing trend of HSCT in these patients, successful outcomes with other transplant options such as match unrelated donor transplants should be considered. Treatment algorithm for Pediatric AA needs to be revised to include other transplant sources. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Chronic Granulomatous Disease: A Rare Hereditary Immuno-deficiency Disorder in a Young Boy with Its Adverse Consequences

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease which results from absence of the NADPH oxidase in the professional phagocytic cells neutrophils, monocytes, macrophages and eosinophils. Deficiency of this oxidase renders the patient liable to infection by bacteria and fungi, and, as the name of the disease suggests, to chronic granulomatous inflammation. Here, a young boy presented with increasing breathlessness and productive cough had recurrent episode of pulmonary infection since his childhood. Repeated Chest X-ray and CT scan showed homogenous opacities at different places of lung in different occasions with bilateral reticulo-nodular opacities. Mulipleoraganisms were isolated from sputum at different times. A nitroblu-tetrazolium test (NBT) was done abroad which was positive and confirmed his diagnosis. Since then, He had prophylactic fluconazol and sulphamethoxazoltrimethoprime daily and pneumocaccal and influenza vaccination regularly and proper treatment of acute infective episodes accordingly. In spite all these measures, repeated infection caused grievous harm to his lung leading to irreversible pulmonary fibrosis and bronchiectasis. As a consequence, he became home bound, oxygen dependant and dependant on regular use of long acting bronchodilators in different form. Hematopoeitic stem cell transplantation was advised which was not affordable for his parents. Now, this young boy is waiting for further assaults to his lungs and further deterioration and ultimate hopeless outcomes.J Bangladesh Coll Phys Surg 2015; 33(3): 156-160

Mycobacterium Mucogenicum in Hematopoeitic Stem Cell Transplant Recipients and in High-Risk Patients Wit H Hematologic Malignancies, 2008-2013

Mycobacterium Mucogenicum in Hematopoeitic Stem Cell Transplant Recipients and in High-Risk Patients Wit H Hematologic Malignancies, 2008-2013

Mucopolysaccharridosis type 1 and the challenges in managing this rare genetic disorder in the resource poor setting

This case report is about a six-year-old Nigerian boy with a rare genetic disorder of attenuated mucopolysaccharidosis type 1 and the challenges that the clinicians face in managing these patients in resource poor settings. This patient presented with short stature with skeletal deformities, poor speech and intellectual impairment. He also had features such as coarse facial features with macroglossia, lichenified, dry thick skin and hepatosplenomegaly. Delay in the diagnosis is a common problem with this rare genetic disorder. Confirmation of the diagnosis and providing the recommended disease-specific therapeutic options such as of enzyme replacement therapy and haematopoeitic stem cell transplantation are the challenges that we face in managing these patients in the resource poor settings.

Hematopoeitic Stem Cell Transplantation in the Developing World: A Case Study of Dhaka Medical College, Bangladesh

INTRODUCTIONWhile hematopoietic stem cell transplantation has become the standard of care for many patients in developed countries, the significant economic investment, infrastructure, and healthcare provider training that are required has prohibited it from being widely adapted. We describe our experience in developing a transplant program at Dhaka Medical College and Hospital (DMCH) in Bangladesh via a partnership with health care providers at the Massachusetts General Hospital (MGH). In 2011, the Minister of Health in Bangladesh became interested in establishing a transplant program at Dhaka Medical College and Hospital (DMCH). DMCH was established in 1946 and has 2300 beds located in two buildings (DMCH-1 with 1800 beds and DMCH-2 with 500 beds). The Bangladesh government and AK Khan Healthcare trust, an interested non-governmental organization (NGO), provided funding for the endeavor. Despite available funding, we faced significant challenges due to limitations in experienced healthcare personnel.METHODSThe DMCH transplantation unit was built on the top floor of DMCH-2 and includes 5 patient rooms, an apheresis area, the hematopathology and general hematology labs, and also includes rooms for leukemia patients who are not currently undergoing transplantation. Three hematologists, two apheresis technicians, one lab technician, and 1 pharmacist from DMCH participated in an exchange program during which they each spent 2-3 months at MGH observing transplantation practices. Additionally, several physicians from MGH traveled to Bangladesh and spent several weeks training DMCH physicians in diagnostics, peripheral blood stem cell collection, transfusion medicine, and management of potential complications.The training of Bangladeshi nurses was an extensive undertaking. In brief, 25 nurses from DMCH were selected to take part in a novel enhanced specialized nurses training program (ESPNTP) run by nurses from MGH, which is described in detail in a separate report. This intensive 12-month program included 3 months of training in English language, 3 months of fundamental nursing training, and 6 months of specialized training in HSCT. Nurses continue to train on an ongoing basis via an advanced curriculum taught by MGH nursing staff.RESULTSThe first transplant was performed on March 10, 2014. Since that time, DMCH has performed 14 autologous stem cell transplants (9 multiple myeloma, 2 diffuse large B-cell lymphoma, acute myelogenous leukemia, Hodgkin's lymphoma, and peripheral T-cell lymphoma). Baseline characteristics, transplant protocol, and summary of results are shown in (Table 1). All patients engrafted successfully (range 9-16 days). Remission was achieved in all cases, and so far there has only been one case of relapsed disease in a patient with multiple myeloma. Significant complications include mucositis (grade II-IV: 12), febrile neutropenia (8), bacteremia (S. epi: 2; P. aeurginosa: 2, MRSA/K. pneumonia: 1), one case of acinetobacter pneumonia, and one case of cytomegalovirus reactivation.DISCUSSIONWe attribute a large part of the program's ability to successfully perform its first transplants within 3 years of conception due not only to available financial support but also logistical and personnel support from collaboration with an established transplant center. A major goal of the current program is to ultimately establish a transplant center capable of performing allogeneic stem cell transplantation, as this would enable treatment of patients with thalassemia, the most common genetic disorder in the country that carries a high burden on the economy. We hope that our experience will encourage more partnership and collaboration between transplant programs in developed countries and those countries who currently lack expertise but could benefit from having this therapeutic modality available. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Immunizations in solid organ and hematopoeitic stem cell transplant patients: A comprehensive review

The Solid Organ Transplantation (SOT) and Haematopoietic Stem Cell Transplantation (HSCT) population is continuously increasing as a result of broader indications for transplant and improved survival. Infectious diseases, including vaccine-preventable diseases, are a significant threat for this population, primarily after but also prior to transplantation. As a consequence, clinicians must ensure that patients are optimally immunized before transplantation, to provide the best protection during the early post-transplantation period, when immunosuppression is the strongest and vaccine responses are poor. After 3–6 months, inactivated vaccines immunization can be resumed. By contrast, live-attenuated vaccines are lifelong contraindicated in SOT patients, but can be considered in HSCT patients at least 2 years after transplantation, if there is no immunosuppression or graft-versus-host-disease. However, because of the advantages of live-attenuated over inactivated vaccines - and also sometimes the absence of an inactivated alternative - an increasing number of prospective studies on live vaccine immunization after transplantation are performed and give new insights about safety and immunogenicity in this population.

A Telephone Support Group for Parents of Children Discharged after Hematopoeitic STEM CELL Transplant

A Telephone Support Group for Parents of Children Discharged after Hematopoeitic STEM CELL Transplant

Travel risk assessment, advice and vaccinations in immunocompromised travellers (HIV, solid organ transplant and haematopoeitic stem cell transplant recipients): A review.

International travellers with immunocompromising conditions such as human immunodeficiency virus (HIV) infection, solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) are at a significant risk of travel-related illnesses from both communicable and non-communicable diseases, depending on the intensity of underlying immune dysfunction, travel destinations and activities. In addition, the choice of travel vaccinations, timing and protective antibody responses are also highly dependent on the underlying conditions and thus pose significant challenges to the health-care providers who are involved in pre-travel risk assessment. This review article provides a framework of understanding and approach to aforementioned groups of immunocompromised travellers regarding pre-travel risk assessment and management; in particular travel vaccinations, infectious and non-infectious disease risks and provision of condition-specific advice; to reduce travel-related mortality and morbidity.

Sclerodermatous Chronic Gvhd in Patients Receiving Tyrosine Kinase Inhibitors after Allogeneic Hematopoeitic Stem Cell Transplant

Sclerodermatous Chronic Gvhd in Patients Receiving Tyrosine Kinase Inhibitors after Allogeneic Hematopoeitic Stem Cell Transplant

Cytomegalovirus reactivation following hematopoietic stem cell transplantation

There is a high prevalence of cytomegalovirus (CMV) seropositivity in developing countries. An apparent risk of CMV reactivation increases following hematopoeitic stem cell transplantation. With effective surveillance and timely treatment using anti-viral therapy, morbidity and mortality associated with CMV reactivation can be reduced. To evaluate the incidence and morbidity associated with CMV reactivation following hematopoeitic stem cell transplantation. We retrospectively analysed 136 hematopoeitic stem cell transplant recipients at our centre for CMV reactivation and their complications. Quantification of CMV-DNA was done by PCR. CMV disease was confirmed histologically via CMV inclusion bodies or immunostaining of biopsy of the affected organ, mainly the gastrointestinal tract. A total of 13 out of 136 patients (9.56%) had CMV reactivation. 6 out of 13 patients had CMV disease, 3 of which died (23.1% of patients with CMV reactivation). CMV reactivation occurred at a median duration of 52.5 days post transplantation (range 35-178 days). The gastrointestinal tract was the organ most commonly affected by CMV. The median follow-up was 14 months (range 6 - 64 months). Through a higher rate of sero-prevalance in developing countries, the incidence of CMV infection following hematopoeitic stem cell transplantation is comparable to that reported in Western literature. Oral valganciclovir was an effective pre-emptive therapy for CMV disease.

Bortezomib Is Highly Effective For Pure Red Cell Aplasia After ABO-Incompatible Hematopoietic Stem Cell Transplantation

Introduction Pure red cell aplasia (PRCA) is an uncommon complication of ABO-incompatible hematopoietic stem cell transplantation. It is characterized by anemia, reticulocytopenia and absence of erythroid precursors in a morphologically normal-appearing bone marrow. Most cases of PRCA resolve spontaneously within weeks to months. A small subset of patients has a protracted disease course requiring continued red blood cell (RBC) transfusions. There is no approved standard of care for PRCA. Tapering of immunosuppressives such as steroids and calcineurin inhibitors, plasma exchange, rituximab, and anti-thymocyte globulin have all been employed with varying success rates. We report a case of PRCA after ABO-incompatible transplant that responded remarkably to treatment with bortezomib. Case Presentation A 60 year old female received a non-myeloablative HLA-matched ABO-mismatched sibling donor transplant for lenalidomide-refractory myelodysplastic syndrome (5q-). She received fludarabine/busulfan conditioning and tacrolimus/methotrexate for GVHD prophylaxis. The donor was blood type A Rh-positive and the recipient was O Rh-positive. The patient's post-transplant course was complicated by delayed engraftment, thrombocytopenia and autoimmune hemolytic anemia. When seen at our institution 22 months post-transplant, she had transfusion-dependent anemia requiring RBC transfusions every 2-3 weeks and reticulocytopenia. Bone marrow biopsy showed erythroid aplasia and preserved hematopoiesis in other cell lines, dysplasia was absent and parvovirus testing was negative. The patient had evidence of complete engraftment based on short tandem repeat analysis. Blood typing reflected transfused type O Rh-negative RBCs. Neither A cells from the donor nor Rh-positive cells from the patient were detected. High titers of anti-A and anti-B isohemagglutinins were detected despite transfusion with washed RBCs to reduce passive transfer. She was treated with prednisone 60mg/day, rituximab 375 mg/m2 weekly x4 and methylprednisolone 1g weekly x6 without response. Eventually, all immunosuppressive medications were discontinued to induce a graft versus recipient response. Two subsequent bone marrow biopsies continued to show nearly absent erythropoiesis, and the rare erythroid cells present lacked the blood group A antigen. Since PRCA was thought to be due to the recipient's plasma cells making anti-A antibodies, bortezomib, a potent inducer of apoptosis in plasma cells, was initiated. Subcutaneous bortezomib 1.3 mg/m2 was administered weekly x4. The patient responded well to therapy. A month after completion of bortezomib, the patient's hemoglobin measured 12.1 g/dL, reticulocyte count was 174 x109/L and IgM and IgG anti-A titers were both &lt; 1. Bone marrow biopsy showed relative erythroid hyperplasia, and the majority of the erythroid precursors expressed blood group A. The patient continues to do well and at the time of her most recent evaluation, her hemoglobin was 13.9 g/dL. She has also remained transfusion-independent. Discussion PRCA after major ABO-incompatible transplant is thought to be caused by persistence of recipient plasma cells that continue to secrete anti-donor isohemagglutinins. Antibody titers may remain elevated for a longer duration in patients receiving non-myeloablative preparatory regimens. Bortezomib is a proteasome inhibitor that selectively induces apoptosis in plasma cells. Bortezomib has been used successfully to treat anti-body mediated rejection in both renal and liver transplant patients. A case of PRCA following ABO-mismatched hematopoietic transplant that was successfully treated with IV bortezomib has also been reported. To our knowledge, this is the first reported case of isohemagglutinin-mediated PRCA after ABO-mismatched transplant that responded favorably to subcutaneous bortezomib. Limitation The lack of long-term follow-up data precludes any assessment about the durability and persistence of response to bortezomib. Conclusion Bortezomib is an effective treatment for patients with PRCA mediated by residual host isohemeagglutinins after ABO-incompatible hematopoietic transplantation. Disclosures: Off Label Use: Our presentation describes the use of bortezomib for treatment of pure red cell aplasia after ABO-incompatible hematopoeitic stem cell transplantation. Vercellotti:Sangart Inc.: Research Funding; Seattle Genetics, Inc.: Research Funding.

Tocilizumab In The Treatment Of Steroid Refractory Graft Versus Host Disease: A Single Institutional Experience

IntroductionAcute graft-versus-host-disease (aGVHD) is a frequent and often lethal complication of allogeneic hematopoeitic stem cell transplant (allo HSCT) despite current prophylactic regimen. It is fueled by the release of pro-inflammatory cytokines such as interleukin-6 (IL-6), leading to damage of host tissues. Front-line treatment with glucocorticoids provide 30-40% complete response. Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) monoclonal antibody that binds to both soluble and membrane-expressed IL-6R, inhibiting IL-6–mediated proinflammatory activity. A case report and a recent small series (8 patients) with steroid refractory GVHD(SR GVHD) showed encouraging single agent activity of tocilizumab(Gergis et al, 2010; Drobyski et al, 2011). We report our experience on 9 patients who had SR aGVHD and received tocilizumab therapy. MethodTocilizumabwas administered intravenously at a dose of 8 mg/kg every 2 to 3 weeks. aGVHD grading and responses were based on consensus criteria (Przepiorka et al, 1995). Patients were monitored for toxicities and infections. ResultsThe median age at transplant was 48 years (range 25-61). Four patients had double cord allo HSCT, 2 had matched related, 2 unrelated (with one 9/10 matched) and 1 haploidentical after a failed cord HSCT. Six patients had received myeloablative and 3 reduced intensity allo HSCT. All but one patient received tacrolimus and methotrexate for aGVHD prophylaxis, and all were in complete remission of their underlying disease at time of aGVHD. Table 1 includes responses and outcomes to tocilizumab therapy. All patients had GI involvement and 6 patients had two organs involved. Median aGVHD grade was 3 (range 3-4). The median time from first aGVHD onset to tocilizumab administration was 44 days (range 14-176). The median number of infusions was 2(1-6). There were no allergic or infusion-related events. Two patients (22%) had a complete response (CR), and two had mixed responses with CR in one organ, but no response in another. Only one of nine patients survived. Six patients (67%) died from aGVHD and its complications, one from CMV and one from septic shock. The median survival from start of tocilizumab was 26 days (range 13-759).Table 1Response and Outcome to TocilizumabPatientDay of aGVHD OnsetOverall Grade of GVHD PriorOrgan Involvement (stage)GVHD Treatments PriorDay to Tocilizumab Administration from Transplant# of DosesOverall Response to TocilizumabCurrent StatusDays Surviving since Tocilizumab InitiationPrimary Cause of Death1+ 263GI (2) Liver ( 2)Steroids Basiliximab+ 706CRDead308Infection- CMV2+304GI (3) Liver (4)Steroids Budesonide+ 1762NRDead25aGVHD3+183GI (4) Liver (1)MMF Budesonide Steroids+ 391GI : NR Liver: CRDead20aGVHD4+603GI (2)Steroids Tacrolimus MMF+ 746CRAlive and disease free759NA5+ 253Skin (2) GI (4)Steroids Sirolimus Budesonide+861NRDead13Alveolar hemorrhage aGVHD6+ 903GI (1) Liver(2)Budesonide Steroids Tacrolimus+2662GI: CR Liver: NRDead26Klebsiella pneumonia, septic shock7+283GI (4)Sirolimus Budesonide Steroids+972NRDead33aGVHD8+433Liver (3) GI(3)MMF Budesonide Steroids+852NRDead16aGVHD9+294GI (4) Liver (4)Steroids MMF budesonide+432NRDead107aGVHD ConclusionsWhile the few tocilizumab treated patients with SR aGVHD reported in the literature have experienced a high response rate of 67%(CR and PR), our limited experience showed a less impressive 22% CR. Although tocilizumab has some activity in the treatment of SR aGVHD, it may not be significantly better than other available agents. Disclosures:Off Label Use: There is currently no standard of practice of steroid-refractory GVHD, every treatment option besides steroids are considered off-label. However, there is evidence to support its use. Tocilizumab Tocilizumab is a humanized anti–IL-6 receptor (anti–IL-6R) monoclonal antibody that binds both soluble and membrane-expressed IL-6R, inhibiting IL-6–mediated proinflammatory activity. In this study, we report our experience with the administration of tocilizumab, an anti-interleukin 6 receptor antibody, in the treatment of steroid refractory GVHD.

Major discrepancies between clinical and postmortem diagnoses in critically ill cancer patients: Is autopsy still useful?

OBJECTIVE:Describe the major discrepancies between the clinical and postmortem findings in critically ill cancer patients admitted to the medical intensive care unit (MICU).MATERIALS AND METHODS:Retrospectively review of the medical records of all cancer patients who were admitted to the MICU and underwent postmortem examination over 6 year period. The records were reviewed for demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, clinical cause of death, and postmortem findings.RESULTS:There were 70 patients who had complete medical records. Mean age was 54.7 years (standard deviation (SD) ±14.8 years). Twenty-six patients had hematopoeitic stem cell transplantation (group I), 21 patients had hematological malignancies (group II), and 23 patients had solid malignancies (group III). The APACHE II score on admission to the MICU was 24.2 ± 8.0. Sixty-seven patients were mechanically ventilated, and the MICU stay was (mean ± SD) 9.0 ± 11.6 days. Major discrepancies between the clinical and postmortem diagnoses (Goldman classes I and II) were detected in 15 patients (21%). The most common missed diagnoses were aspergillosis, pulmonary embolism, and cancer recurrence. There were no differences between groups regarding the rate of major discrepancies.CONCLUSION:Despite the advances in the diagnosis and treatment of critically ill cancer patients, autopsies continue to show major discrepancies between the clinical and postmortem diagnoses. Autopsy is still useful in this patient population.

Transplant‐related mortality following allogeneic hematopoeitic stem cell transplantation for pediatric acute lymphoblastic leukemia: 25‐year retrospective review

BackgroundOver the last 25 years, donor source, conditioning, graft-versus-host disease prevention and supportive care for children undergoing hematopoeitic stem cell transplantation (HSCT) have changed dramatically. HSCT indications for acute lymphoblastic leukemia (ALL) now include high-risk patients in first and subsequent remission. There is a large burden of infectious and pre-HSCT morbidities, due to myelosuppressive therapy required for remission induction. We hypothesized that, despite these trends, overall survival (OS) had increased.ProcedureA retrospective audit of allogeneic pediatric HSCT for ALL was performed in our institution over 25 years. Outcomes for 136 HSCTs were analyzed in three consecutive 8-year periods (Period 1: 1/1/1984–31/8/1992, Period 2: 1/9/1992–30/4/2001, Period 3: 1/5/2001–31/12/2009).ResultsDespite a significant increase in unrelated donor HSCT, event-free and OS over 25 years improved significantly. (EFS 31.6–64.8%, P = 0.0027; OS 41.8–78.9%, P < 0.0001) Concurrently, TRM dropped from 33% to 5% (P = 0.0004) whilst relapse rate was static (P = 0.07). TRM reduced significantly for matched sibling and unrelated cord blood transplantation (UCT) in Period 3 compared with earlier periods (P = 0.036, P = 0.0098, respectively). Factors leading to improved survival in patients undergoing UCT include better matching, higher total nucleated cell doses, and significantly faster neutrophil engraftment. Length of initial HSCT admission was similar over time.ConclusionEFS and OS have increased significantly despite heightened HSCT complexity. This survival gain was due to TRM reduction. Contemporary patients have benefited from refined donor selection and improved supportive care. Overall rates of leukemic relapse post-HSCT are unchanged, and remain the focus for improvement.

The current role of T cell depletion in paediatric stem cell transplantation

Haematopoeitic stem cell transplantation (HSCT) is a curative procedure for children with malignant and non-malignant haematological disease as well as an expanding number of inherited disorders. Most patients lack a human leucocyte antigen-matched related donor, making alternative donors, such as closely matched unrelated donors, unrelated umbilical cord blood donations and haploidentical donors, necessary choices. T cell depletion (TCD) has been employed for over 30 years to reduce the risk of graft-versus-host disease (GvHD) associated with non-genoidentical HSCT. However, until recently overall survival had not improved with TCD due to increased rates of graft failure, disease relapse and delayed immune reconstitution. Recent advances in graft manipulation and reduced toxicity conditioning regimens have offered renewed hope, particularly for children undergoing haploidentical HSCT, where encouraging results have been achieved using negative depletion techniques to retain beneficial accessory cells, which speed immune reconstitution and reduce disease relapse. Translational work building on megadose CD34(+) selected grafts, including pathogen-specific immunotherapy, suicide gene therapy and other adoptive cellular immunotherapies, has also offered improved outcomes for such patients.

Primary Hemophagocytic Lymphohistiocytosis and Hematopoeitic Stem Cell Transplantation in Iran

Primary Hemophagocytic Lymphohistiocytosis and Hematopoeitic Stem Cell Transplantation in Iran