Role of Endoscopic Techniques in the Diagnosis of Complications of Allogeneic Hematopoietic Stem Cell Transplantation: A Review of the Literature.

Allogeneic stem cell transplantation (Allo-SCT) implies that a donor and a recipient are not genetically identical. Allo-SCT is used to cure a variety of conditions, including hematologic malignancies using the graft versus tumor effect, nonmalignant hematologic, immune deficiencies, and, more recently, genetic disorders and inborn errors of metabolism. Given the immunosuppressive and myeloablative nature of some of the conditioning chemotherapy regimens used during the Allo-SCT, patients are often at high risk of infection, including viral infections affecting the gastrointestinal tract, following the transplant. Furthermore, other complications such as hepatic sinusoidal obstruction syndrome (SOS) or graft-versus-host disease may occur post-transplant and may require endoscopy to assist in the diagnosis. This review will provide newer insights into the importance of endoscopic techniques in the diagnosis of post-Allo-SCT complications with a focus on safety and timing.

Characteristics and distinct prognostic determinants of individuals with hepatosplenic T-cell lymphoma over the past two decades.

BACKGROUND: Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive peripheral T-cell lymphoma with historically dismal outcomes, representing less than one percent of non-Hodgkin lymphomas. Given its rarity, the true incidence of HSTCL is unknown and most data have been extrapolated through case reports. To the best of our knowledge, the largest and most up to date study addressing the epidemiology and outcomes of patients with HSTCL in the United States covered a period from 1996 to 2014, with a sample size of 122 patients. AIM: To paint the most updated epidemiological picture of HSTCL. METHODS: A total of 186 patients diagnosed with HSTCL, between 2000 and 2017, were ultimately enrolled in our study by retrieving data from the Surveillance, Epidemiology, and End Results database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of HSTCL. Variables with a P value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio of greater than 1 representing adverse prognostic factors. RESULTS: Male gender was the most represented. HSTCL was most common in middle-aged patients (40-59) and less common in the elderly (80+). Non-Hispanic whites (60.75%) and non-Hispanic blacks (20.97%) were the most represented racial groups. Univariate Cox proportional hazard regression analysis of factors influencing all-cause mortality showed a higher OM among non-Hispanic black patients. CSM was also higher among non-Hispanic blacks and patients with distant metastasis. Multivariate Cox proportional hazard regression analysis of factors affecting CSM revealed higher mortality in patients aged 80 or older and non-Hispanic blacks. CONCLUSION: Overall, the outlook for this rare malignancy is very grim. In this retrospective cohort study of the United States population, non-Hispanic blacks and the elderly had a higher CSM. This data highlights the need for larger prospective studies to investigate factors associated with worse prognosis in one ethnic group, such as treatment delays, which have been shown to increase mortality in this racial/ethnic group for other cancers.

Immune reconstitution, vaccine responses, and rituximab use after ex-vivo CD34-selected myeloablative allogenic hematopoietic cell transplantation.

Myeloablative T cell depleted (CD34-selected) hematopoietic cell transplantation (HCT) is associated with less acute and chronic graft versus host disease (GVHD). We aimed to examine vaccine responses in relation to immune reconstitution and post HCT rituximab administration in this population. This single center retrospective study included 251 patients with hematological malignancies who received a first CD34-selected HCT between 2012 and 2015. Of 251 patients, 190 were alive 1 year after HCT. Among the entire population, 77 (30.7%) patients were vaccinated. After vaccine administration, 35/44 (80%), 30/75 (40%), 27/36 (75%), 33/65 (51%), 34/51 (51%), 22/28 (79%) and 20/34 (59%) of evaluable patients had protective antibody titers for haemophilus influenzae type B (Hib), Pneumococcus, Tetanus, Diphtheria, Pertussis, hepatitis A (HAV), and hepatitis B (HBV) respectively. Responders to the pneumococcal vaccine had a higher CD45RA T cell count than non responders, with 12/18 patients (66.7%) vs 11/32 (34.4%) p = 0.04. For pneumococcal vaccine, there was also a trend to higher total lymphocyte B cell count in responders vs non responders p = 0.06. Rituximab post HCT was given to 59/251 (23.5%) patients. No difference was found in immune reconstitution patterns for rituximab use between vaccine responders and not. Recipients of CD34-selected HCT may respond to vaccination, and T and B cell subsets could be useful to predict vaccine response.

A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia.

ABSTRACT: The curative potential of allogeneic hematopoietic transplantation (allo-HCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse. Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin, which has significant activity against ALL. We hypothesized that low-dose INO would be safe and feasible after allo-HCT. Therefore, we conducted a phase 1 study to determine the dose and safety in this setting. Patients were eligible if they were aged 16 to 75 years, had undergone allo-HCT for CD22+ ALL, were in complete remission (CR) after allo-HCT, had high risk of recurrence, were between day 40 and 100 after allo-HCT with adequate graft function, and did not have a history of sinusoidal obstruction syndrome (SOS). The objectives of this trial were to define INO maximum tolerated dose (MTD), to determine post-allo-HCT INO safety, and to measure 1-year progression-free survival (PFS). The trial design followed a "3+3" model. The treatment consisted of INO given on day 1 of 28-day cycles. Dose levels were 0.3 mg/m2, 0.4 mg/m2, 0.5 mg/m2, and 0.6 mg/m2. Median age was 44 years (range, 17-66 years; n = 18). Disease status at transplantation was first CR (n = 14) or second CR or beyond (n = 4). Preparative regimen was of reduced intensity in 72% of patients who received transplantation. Most common toxicity was thrombocytopenia. There were no instances of SOS; the MTD was 0.6 mg/m2. One-year nonrelapse mortality was 5.6%. With a median follow-up of 18.1 months (range, 8.6-59 months) 1-year post-allo-HCT PFS and overall survival is 89% and 94%, respectively. Low-dose INO has a favorable safety profile and was associated with high rates of 1-year PFS. This trial was registered at www.clinicaltrials.gov as #NCT03104491.

The association of cobalturia with cobaltism symptoms a prospective blinded study of 229 post-arthroplasty patients.

INTRODUCTION: Cobalt is a mitochondrial toxin, clinical cobaltism manifests with constitutional, neurologic, and cardiovascular symptomatology. Cobalt's severe toxidrome is known through case reports from extreme wear or corrosion of cobalt-chromium arthroplasty components. However, the spectrum and epidemiology of orthopedic-implant cobaltism and its relationship to duration and degree of cobalt exposure are not well defined. METHODS: The relationship of urine-cobalt concentration and duration of exposure to cobalt-chromium joint implants and cobaltism symptomatology were prospectively studied in 229 patients. Subjects received a Cobaltism-Symptom-Inventory-Score (CSIS) based on a protocolized interview and examination followed by a spot urine-cobalt measurement. RESULTS: 129 (56%) subjects were cobalturic (urine-cobalt ≥1.0 ppb). 122 (53%) subjects had a CSIS of >2, this status significantly associates with cobalturia. Median [IQR] urine-cobalt in the subjects with a CSIS >2 was 4.1[1.1-17.0] ppb compared to 0.5[0.5-1.4] ppb in subjects with CSIS ≤ 2. Cobalturia has a sensitivity of 0.69, a specificity of 0.77, and a positive predictive value of 0.74 for a CSIS of >2. The product of years-exposed to a cobalt-chromium implant and urine-cobalt by quartiles significantly positively associates with the Cobaltism-Symptom-Inventory-Score. CONCLUSION: A urine-cobalt of ≥1 ppb likely indicates adverse systemic exposure to orthopedic-implant generated cobalt. Cobaltism severity as quantified by the CSIS significantly correlates with the product of spot urine-cobalt concentration and years-exposed to a cobalt-chromium orthopedic-implant indicating a dose-response relationship. Medical provider and public awareness of orthopedic-implant cobaltism is vital because tens-of-millions are at-risk and early cobaltism is reversible. Further use of cobalt-chromium orthopedic-implants should be questioned given cobaltism becomes clinically apparent at a spot urine-cobalt of 1 ppb or greater. Monitoring of patients with high-risk cobalt-chromium orthopedic-implants appears to be indicated.