Hemopoietic Stem Cell Transplantation Research Articles

Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial

Old age and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations in patients with acute myeloid leukaemia are associated with early relapse and poor survival. Quizartinib is an oral, highly potent, and selective next-generation FLT3 inhibitor with clinical antileukaemic activity in relapsed or refractory acute myeloid leukaemia. We aimed to assess the efficacy and safety of single-agent quizartinib in patients with relapsed or refractory acute myeloid leukaemia. We did an open-label, multicentre, single-arm, phase 2 trial at 76 hospitals and cancer centres in the USA, Europe, and Canada. We enrolled patients with morphologically documented primary acute myeloid leukaemia or acute myeloid leukaemia secondary to myelodysplastic syndromes and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 into two predefined, independent cohorts: patients who were aged 60 years or older with relapsed or refractory acute myeloid leukaemia within 1 year after first-line therapy (cohort 1), and those who were 18 years or older with relapsed or refractory disease following salvage chemotherapy or haemopoietic stem cell transplantation (cohort 2). Patients with an FLT3-ITD allelic frequency of more than 10% were considered as FLT3-ITD positive, whereas all other patients were considered as FLT3-ITD negative. Patients received quizartinib once daily as an oral solution; the initial 17 patients received 200 mg per day but the QTcF interval was prolonged for more than 60 ms above baseline in some of these patients. Subsequently, doses were amended for all patients to 135 mg per day for men and 90 mg per day for women. The co-primary endpoints were the proportion of patients who achieved a composite complete remission (defined as complete remission + complete remission with incomplete platelet recovery + complete remission with incomplete haematological recovery) and the proportion of patients who achieved a complete remission. Efficacy and safety analyses included all patients who received at least one dose of quizartinib (ie, the intention-to-treat population). Patients with a locally assessed post-treatment bone marrow aspirate or biopsy were included in efficacy analyses by response; all other patients were considered to have an unknown response. This study is registered with ClinicalTrials.gov, number NCT00989261, and with the European Clinical Trials Database, EudraCT 2009-013093-41, and is completed. Between Nov 19, 2009, and Oct 31, 2011, a total of 333 patients were enrolled (157 in cohort 1 and 176 in cohort 2). In cohort 1, 63 (56%) of 112 FLT3-ITD-positive patients and 16 (36%) of 44 FLT3-ITD-negative patients achieved composite complete remission, with three (3%) FLT3-ITD-positive patients and two (5%) FLT3-ITD-negative patients achieving complete remission. In cohort 2, 62 (46%) of 136 FLT3-ITD-positive patients achieved composite complete remission with five (4%) achieving complete remission, whereas 12 (30%) of 40 FLT3-ITD-negative patients achieved composite complete remission with one (3%) achieving complete remission. Across both cohorts (ie, the intention-to-treat population of 333 patients), grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients were febrile neutropenia (76 [23%] of 333), anaemia (75 [23%]), thrombocytopenia (39 [12%]), QT interval corrected using Fridericia's formula (QTcF) prolongation (33 [10%]), neutropenia (31 [9%]), leucopenia (22 [7%]), decreased platelet count (20 [6%]), and pneumonia (17 [5%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (126 [38%] of 333; 76 treatment related), acute myeloid leukaemia progression (73 [22%]), pneumonia (40 [12%]; 14 treatment related), QTcF prolongation (33 [10%]; 32 treatment related), sepsis (25 [8%]; eight treatment related), and pyrexia (18 [5%]; nine treatment related). Notable serious adverse events occurring in less than 5% of patients were torsades de pointes (one [<1%]) and hepatic failure (two [1%]). In total, 125 (38%) of 333 patients died within the study treatment period, including the 30-day follow-up. 18 (5%) patients died because of an adverse event considered by the investigator to be treatment related (ten [6%] of 157 patients in cohort 1 and eight [5%] of 176 in cohort 2. Single-agent quizartinib was shown to be highly active and generally well tolerated in patients with relapsed or refractory acute myeloid leukaemia, particularly those with FLT3-ITD mutations. These findings confirm that targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor is a promising clinical strategy to help improve clinical outcomes in patients with very few options. Phase 3 studies (NCT02039726; NCT02668653) will examine quizartinib at lower starting doses. Ambit Biosciences/Daiichi Sankyo.

Foscarnet treatment of cytomegalovirus infection in haploidentical or unrelated donor transplants

We studied 97 patients who developed cytomegalovirus (CMV) viremia following an allogeneic hemopoietic stem cell transplant (HSCT) between 2010 and 2015, treated with foscarnet, with the aim of assessing efficacy and safety. The donor was unrelated in 30 patients (UD) and a family HLA-haploidentical donor (HAPLO) in 67 patients: the former (UD) received a prophylaxis for graft-versus-host disease (GvHD), based on antithymocyte globulin (ATG); the latter (HAPLO) received GvHD prophylaxis, based on post-transplant cyclophosphamide (PT-CY). Renal and hematological toxicity were defined according to NCI-CTCAE4 criteria. In univariate analysis, CMV response was 84% in HAPLO vs 59% in UD grafts (p = 0.01) and 90 vs 66% (p = 0.02) for patients with a CMV viral load within or over the median value. In multivariate analysis, the CMV viral load was the strongest predictor of response to foscarnet (p = 0.02), followed by donor type (p = 0.06). Renal impairment developed in 14% of the patients. Overall survival was 69%:, advanced phase at transplant (p = 0.01) and ATG-based regimens (p = 0.02), were the only two predicting factor. In conclusion, CMV response to foscarnet treatment is predicted by a lower CMV load and GvHD prophylaxis. Renal toxicity of foscarnet is not a limiting factor.

FEATURES OF DEVELOPMENT, COURSE AND OUTCOME OF ACUTE KIDNEY INJURY AFTER HEMOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN (LITERATURE REWIEV)

In literature review are presented the epidemiology, causes, features of courses, outcome of acute kidney injury after hemopoietic stem cell transplantation in children.

Prenatal and preimplantation diagnosis of hemoglobinopathies.

The hemoglobinopathies, as a group, are one of the most common serious monogenic diseases in the world. An accepted and widely adopted approach to reduce the number of new cases involves carrier-screening programs, with the option of prenatal diagnosis (PND) or preimplantation diagnosis (preimplantation genetic testing for monogenic disease, PGT-M) for carrier couples. The aim of PND is to provide an accurate result as early in pregnancy as possible, which necessitates prior identification of the parental disease-causing mutations, as well as safe and timely biopsy of fetal material. PGT-M aims to characterize the genetic status of in vitro fertilized embryos during assisted reproductive technology (ART), in a few cells biopsied from oocytes/zygotes or embryos, in order to initiate an unaffected pregnancy. Another application of PGT-M is preimplantation genetic diagnosis for human leukocyte antigen (PGD-HLA), which, in addition to identifying unaffected embryos, also characterizes the embryos that are HLA compatible with an existing affected child requiring a hemopoietic stem cell transplantation (HSCT). This review outlines the current practices related to these procedures, with emphasis on the aspects related to laboratory techniques. Finally, future prospects related to developments in noninvasive prenatal diagnosis are discussed.

CXCL12/CXCR4 Signaling Enhances Human PSC-Derived Hematopoietic ProgenitorFunction and Overcomes Early InVivo Transplantation Failure.

SummaryHuman pluripotent stem cells (hPSCs) generate hematopoietic progenitor cells (HPCs) but fail to engraft xenograft models used to detect adult/somatic hematopoietic stem cells (HSCs) from donors. Recent progress to derive hPSC-derived HSCs has relied on cell-autonomous forced expression of transcription factors; however, the relationship of bone marrow to transplanted cells remains unknown. Here, we quantified a failure of hPSC-HPCs to survive even 24 hr post transplantation. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and function. Ectopic CXCR4 conferred CXCL12 ligand-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis, hematopoietic progenitor capacity, and survival and proliferation following in vivo transplantation. This was accompanied by a transcriptional shift of hPSC-HPCs toward somatic/adult sources, but this approach failed to produce long-term HSC xenograft reconstitution. Our results reveal that networks involving CXCR4 should be targeted to generate putative HSCs with in vivo function from hPSCs.

Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial

Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age (<50 vs ≥50 years) and intended duration of antiviral prophylaxis after transplantation (≤3 months vs >3 to ≤6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5-60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all randomised participants who received at least one dose of vaccine and had follow-up data. A prespecified vaccine efficacy success criterion required the lower bound of the 95% CI be higher than 25% for the relative reduction of the hazard ratio of herpes zoster infection in participants given the vaccine from one of the consistency lots compared with those given placebo. This trial is registered on ClinicalTrials.gov (NCT01229267) and EudraCT (2010-020150-34). Between Dec 7, 2010, and April 25, 2013, 560 participants were randomly assigned to the vaccine consistency lot group, 106 to the high-antigen lot group, and 564 to the placebo group. 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end, mostly because of death or withdrawal. 51 participants were excluded from the primary efficacy endpoint analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 [4%] in the vaccine consistency lot group, and 29 [5%] in the placebo group). Mean follow-up for efficacy was 2·4 years (SD 1·3) in the vaccine consistency lot group and 2·3 years (SD 1·3) in the placebo group. 42 (8%) of 538 participants in the vaccine consistency lot group (32·9 per 1000 person-years) and 113 (21%) of 535 in the placebo group (91·9 per 1000 person-years) had a confirmed case of herpes zoster. The estimated vaccine efficacy was 63·8% (95% CI 48·4-74·6), meeting the pre-specified success criterion. For the combined vaccine groups versus the placebo group, the proportion of patients with serious adverse events (216 [33%] of 657 vs 181 [33%] of 554; risk difference 0·2%, 95% CI -5·1 to 5·5) and serious vaccine-related adverse events (five [1%] vs five [1%]; risk difference 0·1%, -1·4 to 1·1) were similar. Vaccine-related injection-site adverse events occurred more frequently in participants given vaccine than those given placebo (191 [29%] vs 36 [7%]; risk difference 22·6%, 95% CI 18·5-26·6; p<0·0001). This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated. Merck & Co., Inc.

Defining clinically relevant measures of iron overload around haemopoietic stem cell transplantation

Defining clinically relevant measures of iron overload around haemopoietic stem cell transplantation

I126 The present: refinement and delivery of haemopoietic stem cell transplantation in systemic sclerosis

i126 The present: refinement and delivery of haemopoietic stem cell transplantation in systemic sclerosis

Vaginal development and sexual functioning in young women after stem cell transplantation, chemotherapy, and/or radiotherapy for childhood hematological diseases.

To study vaginal development and sexual functioning in young women after childhood hemopoietic stem cell transplantation (HSCT) and radio/chemotherapy. Observational case-control study on 30 young sexually active women survived after HSCT and/or radio/chemotherapy for childhood malignancies or hematologic diseases and 48 controls matched for age. Female Sexual Function Index was lower (median 24.05, IQR = 17.30-28.30 vs. 29.00, IQR = 25.30-31.40, p = 0.001), Female Sexual Distress Scale higher (median 16.00, IQR = 8.00-23.00 vs. 2.00, IQR = 0.00-4.00, p < 0.001), vaginal length shorter (mean difference = 21.1 mm; 95% CI = 19.3-23, p < .001) and vaginal maturation index worst in cases than in controls. Subjects treated by irradiation before HSCT had lower FSFI (median 21.85, IQR = 9.60-31.10 vs. 24.90, IQR = 17.30-28.30) and shorter vaginal length (median 45.55, IQR = 42.60-45.80 vs. 50.10, IQR = 45.30-52.90) compared to those who had not received conditioning treatment (p-values = 0.004 and p = 0.05, respectively). Compared to untreated subjects, women receiving hormonal replacement therapy had higher overall FSFI (p = 0.02), lower FSDS (0.04), and better VMI. Gonadotoxic therapies have adverse effects on vaginal development, sexual functioning, and distress in young females. Hormonal replacement therapy should be shortly considered after main gonodatoxic treatments to improve vaginal and sex health.

Acute myeloid leukaemia relapsing after allogeneic haemopoietic stem cell transplantation: prognostic factors and impact of initial therapy of relapse.

We sought to determine factors associated with the overall survival from relapse (OSR) of acute myeloid leukaemia (AML) after allogeneic haemopoietic stem cell transplantation (alloHSCT) and the effect of first salvage therapy and subsequent graft-versus-host disease (GVHD) on OSR. Data on 386 patients from nine Australian centres with relapsed AML post-alloHSCT were collected retrospectively. OSR was calculated using the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the log-rank test and proportional hazards modelling, respectively and a prognostic index for OSR was derived from multivariate modelling. On multivariate analysis, relapse within 6 months (hazard ratio (HR) 2.4, P < 0.001) and grade 3-4 acute GVHD preceding relapse (HR 2.0, P = 0.004), were associated with inferior OSR. Patients with 1-2 factors had inferior OSR compared to those with zero factors (all patients: HR 2.3, P < 0.001, patients given salvage: HR 1.8, P < 0.001). The first salvage therapy used post-relapse was donor cell therapy (DCT) (second alloHSCT or donor lymphocyte infusion) in 75, re-induction chemotherapy (CT) in 103, radiotherapy in 8 and interferon-α in 6. Although re-induction CT death rate was low (2%), survival after CT was inferior to DCT (HR 1.9, P < 0.001). No survival benefit was seen for patients who developed GVHD following salvage therapy (P = 0.405). Patients with AML who relapse beyond 6 months from alloHSCT without prior grade 3-4 acute GVHD have a better outcome from salvage therapy. Salvage treatments employing DCT as the initial treatment of AML relapse confer a survival advantage over CT.

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention.

Objective:The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey.Materials and Methods:A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with β-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%).Results:The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all β-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999.Conclusion:While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.

Effects of two doses of anti-T lymphocyte globulin-Fresenius given after full-match sibling stem cell transplantation in acute myeloblastic leukemia patients who underwent myeloablative fludarabine/busulfan conditioning

Objective/backgroundAnti-T lymphocyte globulin Fresenius (rATG-F; ATG-Fresenius) and antithymocyte globulin (thymoglobulin), which are included in transplant protocols, are used to reduce the risk of chronic graft-versus-host disease (cGVHD) or suppress allograft rejection. Available clinical studies have been conducted in heterogenous patient populations and with different administration protocols including stem cell sources. Additionally, the pharmacokinetics of ATG is variable, and the clinically effective dose of rATG-F, in particular, is not exactly known. The aim of the study was to investigate the clinical outcomes of acute myeloid leukemia (AML) patients who underwent hemopoietic peripheral stem cell transplantation from full-matched sibling donors and given two different doses of r-ATG-F. MethodsThis was a single-center, retrospective chart review conducted between July 2005 and July 2016. Sixty-nine consecutive AML patients who underwent transplant with fludarabine- and busulfan-based conditioning were included in the study. Patients in Group 1 received 15 mg/kg body weight rATG-F to 2013 (n = 46), and Group 2 received 30 mg/kg of rATG-F dose begining in 2013 to reduce to cGVHD (n = 23). Cyclosporine and methotrexate were used to treat acute GVHD (aGVHD) prophylaxis. Outcome parameters were compared between the groups. ResultsAlthough the recommended dose r-ATG-F had led to a decrease in the cumulative incidence of cGVHD (27 [58.7%] vs. 8 [34.8%]; p = .03), it also increased the infection rate at 1 year (3 [6.5%] vs. 4 [17.4%]; p = .02). The two groups were similar in terms of engraftment time, aGVHD, relapse, nonrelapse mortality, and rATG-F-related toxicity. A Cox regression model revealed that aGVHD III–IV was associated with increased nonrelapse mortality at 1 year (hazard ratio = 18.2; 95% confidence interval, 1.667–199.255; p = <.02). No patients developed rATG-F-related severe adverse events (Common Terminology Criteria grade 4 or 5). ConclusionDose difference of rATG-F did not influence survival parameters; however, increasing the dose to 30 mg/kg seems to be effective for reducing cGVHD with an increase in infection rate requiring close monitoring of infections in AML patients who received myeloablative fludarabine/busulfan conditioning.

Эмоциональное состояние и стратегии совладания подростков с онкогематологическими заболеваниями

The article presents data on the study of emotional state characteristics and coping strategies of adolescents in the stressful situation of oncohematological diseases treatment. Two equalized by socio-demographic and clinical parameters groups of patients 11-18 were examined. The experimental group consisted of 28 adolescents undergoing treatment with hemopoietic stem cell transplantation (HSCT) (M = 14.25, SD = 2.20, M: 57.1%, F: 42.9%). The control group consisted of 30 adolescents undergoing chemotherapy (M = 13.71, SD = 2.12, M: 53.3%, F: 46.7%). The psychological state of adolescents in the course of treatment by НSCТ, in comparison with the state of adolescents of the control group, which is characterized by a significantly higher level of distress and anxiety. Significant differences in the use of coping strategies with stress in patients of the two groups were obtained. Adolescents of the experimental group use a less extensive repertoire of productive coping strategies, often use such an ineffective strategy as "discharge" These differences may be associated with less availability, as well as an increase in depletion of various coping resources under special treatment conditions by the НSCТ. The results of the study confirmed that НSCТ is objectively and subjectively more stressful, which indicates the need for additional monitoring of both the psychological state and the need for psychological care for patients in this group, the development of specialized programs for psychological support for transplantation.

Spectrum of issues and outcomes of critically Ill pediatric hemopoietic stem cell transplant recipients requiring admission to intensive care unit in a tertiary care hospital in India

Background : Hematopoietic stem cell transplantation (HSCT) is a lifesaving therapeutic option for children with multiple hematologic, oncologic, and immunologic disorders. However, a large proportion of children undergoing HSCT develop complications that necessitate admission to the pediatric intensive care unit (PICU). Methods : Study design: Retrospective chart review Setting and patient description: All children younger than 18 years of age, who received an HSCT in our hospital between August 2013 and June 2015, were identified from the HSCT database. Patients admitted to the ICU after HSCT were identified from a prospectively maintained ICU database. Patient data collected from medical charts included demographic information, pre-existing diagnosis requiring HSCT, number and type of transplantation, type of donor and source of stem cells, any complications if associated. Consent: Prior to the start of the HSCT procedure, all parents, and when appropriate, all patients, gave written informed consent to analyse clinical data for study purposes. PICU data: Indication for PICU admission, diagnosis, ventilator and inotrope requirement, if applicable and organ dysfunction. The outcome of patients, whether survival or death at discharge and follow up at 28days were done. Statistics: Descriptive and inferential statistical analysis has been carried out in the present study using SPSS 15.0. Results : During the study period, 141 children received HSCT of which 28 children required PICU admission on 33 occasions accounting for a PICU admission rate of 23.4%. Majority of patients were in the age group of 1-5yrs - 20 (60.6%), followed by 6-10yrs- 5(15.2%). The majority had a non-malignancy indication for HCST -22 (66.6%), of which thalassemia was the commonest diagnosis, followed by severe combined immunodeficiency (SCID) and adreno-leucodystrophy. The most common indications for PICU admission were seizures (n=10, 30.3%), hypotension (n=7, 21%) and respiratory distress (n=6, 18%). Sepsis or severe sepsis occurred in 75%, with pneumonia being the commonest focus in 44%. We observed a 64% (n=21) survival following PICU admission. While 26 (80%) patients with severe sepsis were culture positive, gram-negative bacilli were the commonest organisms. The most common organ dysfunction observed was respiratory failure (n=20, 60%) followed by neurological dysfunction (n=15, 45.5%). Acute kidney injury was observed in 11 (33%) patients, of which 5 (45%) required renal replacement therapy. Circulatory failure with hypotension had the highest risk of mortality. Other risk factors significantly associated with mortality were kidney injury(p-0.005), duration of mechanical ventilation (>5days)(p-0.009) and higher inotropic score (>10)(p- 0.004)). Septic shock was the most common cause of mortality in 6 (50%), followed by GVHD in 3 (25%) children. PICU survival was unaffected by the age characteristics, underlying condition or the type of HSCT. Conclusion : Immunocompromised children who need PICU admission after HSCT have high risk of death, especially in the presence of multi-organ failure, of which circulatory dysfunction appeared to have the greatest risk. In our study we observed 64% survival, which is better than previous studies in similar cohorts and comparable to western data. However, survival can be optimized by aggressive multidisciplinary ICU support.

Contemporary analysis of functional immune recovery to opportunistic and vaccine-preventable infections after allogeneic haemopoietic stem cell transplantation.

ObjectivesInfections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT.MethodsTwenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3‐, 6‐, 9‐, and 12‐months post‐alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping.ResultsMedian absolute T‐ and B‐cell counts were below normal from baseline until 9‐ to 12‐months post‐alloHSCT. Median absolute CD4+ T‐cell counts recovered at 12‐months post‐alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein‐Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL‐6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T‐cell count correlated with IL‐1β (P = 0.045) and CD8+ T‐cell count with IFNγ (P = 0.013) and IL‐1β (P = 0.012). The NK‐cell count correlated with IL‐1β (P = 0.02) and IL‐17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow‐up.ConclusionsThis pilot study demonstrates that immune recovery can be measured using CD4+ T‐cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL‐1β, IL‐4, IL‐6, IL‐17, IL‐21, IL‐31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post‐alloHSCT.

Maintenance therapy of multiple myeloma: is there a best drug or combinations?

Multiple myeloma (MM) is a kind of common hematologic neoplasms. The application of new drugs and autologous hemopoietic stem cell transplantation can significantly improve the response rate of MM. However, as it is impossible to eradicate the minimal residual disease, recurrence is unavoidable. Maintenance therapy has the potential to increase remission degree, thus lengthening the progression-free survival and overall survival time of MM patients. Key words: Multiple myeloma; Maintenance therapy; Minimal residual disease; Immunomodulator; Protease inhibitor

Current situation and correlation between health literacy and uncertainty in illness among patients after hemopoietic stem cell transplantation

Objective To investigate the clinical status of health literacy and uncertainty in illness among patients after hemopoietic stem cell transplantation and to analyze the influence of health literacy on uncertainty in illness. Methods Inpatients after hemopoietic stem cell transplantation in Hematology Department of He'nan Provincial People's Hospital were selected as subjects by convenience sampling from January 2015 to March 2017. The cross-sectional study was conducted with the health literacy scale and Mishel uncertainty in illness scale (MUIS) . Simple correlation, correlation analysis and hierarchical regression analysis were used to explore the influence of health literacy on uncertainty in illness. Results The score of MUIS of patients after hemopoietic stem cell transplantation was (76.69±27.65) along with more than 80% of patients with a medium or a high level of uncertainty in illness. The score of health literacy was (92.33±14.58) with more than 90% of patients with a low or medium level of health literacy. There were significant differences in the score of uncertainty in illness among patients with different education levels and average monthly earnings (F=4.243, 5.746; P<0.05) . The total score of health literacy as well as the score of basic health care literacy, disease control and prevention literacy and first aid literacy had negative correlations with the total score and scores of dimensions of uncertainty in illness (r=-0.298--0.363; P<0.05) . Hierarchical regression analysis showed that dimensions of health literacy had a single predictive power on uncertainty in illness along with explaining 42.8% of the variance separately. Conclusions The uncertainty in illness among patients after hemopoietic stem cell transplantation is in a high level and the health literacy is in a bad level. Beyond education levels and average monthly earnings, health literacy has influence on uncertainty in illness separately. Key words: Hematopoietic stem cell transplantation; Health literacy; Uncertainty in illness

Initial Results of Peripheral-Blood Stem-Cell Mobilization, Collection, Cryopreservation, and Engraftment After Autologous Transplantation Confirm That the Capacity-Building Approach Offers Good Chances of Success in Critical Contexts: A Kurdish-Italian Cooperative Project at the Hiwa Cancer Hospital, Sulaymaniyah.

IntroductionAt Hiwa Cancer Hospital (Sulaymaniyah, Iraqi Kurdistan) after the center was started by a cooperative project in June 2016, autologous transplantation was developed.Patients and MethodsTo develop the project, the capacity-building approach was adopted, with on-site training and coaching of personnel, educational meetings, lectures, on-the-job training, and the implementation of quality management planning.ResultsHere, we report initial results of peripheral-blood stem-cell mobilization and collection of the first 27 patients (age 12 to 61 years; 19 males and 8 females; multiple myeloma, n = 10; plasma cell leukemia, n = 1; Hodgkin lymphoma, n = 12; non-Hodgkin lymphoma, n = 3; and acute myeloid leukemia, n = 1). Only three (11.5%) of 26 patients experienced a failure of mobilization. A median of 6.1 × 106/kg CD34-positive cells per patient were collected (range, 2.4 to 20.8), with two apheretic runs. Twenty-four patients underwent autologous transplantation. All but one transplantation engrafted fully and steadily, with 0.5 and 1.0 × 109/L polymorphonucleates on day 10.5 (range, 8 to 12) and day 11 (range, 9 to 15), respectively, and with 20 and 50 × 109/L platelets on day 13 (range, 10 to 17) and day 17 (range, 2 to 44), respectively. More than 95% of patients are projected to survive 1 year after autograft.ConclusionThese data are the result of an Italian effort to establish in Iraqi Kurdistan a leading center for hemopoietic stem-cell transplantation. The capacity building approach was used, with on-site training and coaching as instruments for the development of provider ability and problem solving. With future limitations for immigration, this method will be helpful, especially in the field of high-technology medicine.

Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study

Haemopoietic stem-cell transplantation (HSCT) eradicates host haemopoiesis before venous infusion of haemopoietic stem cells (HSCs). The pathway to cellular recovery has been difficult to study in human beings because of risks associated with interventions during aplasia. We investigated whether 18F-fluorothymidine (18F-FLT) imaging was safe during allogenic HSCT and allowed visualisation of early cellular proliferation and detection of patterns of cellular engraftment after HSCT. Eligible patients were aged 18-55 years, had high-risk haematological malignancies. All patients underwent myeloablation followed by HSCT. The imaging primary endpoint was detection of early subclinical engraftment after HSCT with 18F-FLT PET or CT. Imaging was done 1 day before and 5 or 9, and 28 days, and 1 year after HSCT. This study is registered with ClinicalTrials.gov, number NCT01338987. Between April 1, 2014, and Dec 31, 2015, 23 patients were enrolled and assessable for toxic effects after completing accrual. 18F-FLT was not associated with any adverse events or delayed engraftment. 18F-FLT imaging objectively identified subclinical bone-marrow recovery within 5 days of HSC infusion, which was up to 20 days before engraftment became clinically evident. Quantitatively, 18F-FLT intensity differed significantly between myeloablative infusion before HSCT and subclinical HSC recovery (p=0·00031). 18F-FLT biodistribution over time revealed a previously unknown path of cellular recovery of haemopoiesis in vivo that mirrored fetal ontogeny. 18F-FLT allowed quantification and tracking of subclinical bone-marrow repopulation in human beings and revealed new insights into the biology of HSC recovery after HSCT. National Institutes of Health, Ben's Run/Ben's Gift, Albert and Elizabeth Tucker Foundation, Mex Frates Leukemia Fund, Jones Family fund, and Oklahoma Center for Adult Stem Cell Research.

The effect of haemopoietic stem cell transplantation on the ocular phenotype in mucopolysaccharidosis type I (Hurler).

To determine whether the ocular phenotype in patients with mucopolysaccharidosis type I (MPSI) Hurler is affected by the efficacy of previous haemopoietic stem cell transplantation (HSCT). A retrospective cohort study of patients with MPSI who had undergone treatment with HSCT. Ocular phenotype was documented for each patient and compared to levels of biomarkers representing efficacy of previous transplantation. Assessment of visual acuity (VA), severity of corneal clouding and the presence of optic neuropathy or retinopathy. Biomarker assessment included dermatan sulphate/chondroitin sulphate (DS/CS) ratio and iduronidase enzyme level. Severe corneal clouding was significantly greater in patients with lower iduronidase levels (p=0.023) and raised DS/CS ratio (R2 =0.28 p=0.043). Better VA was related to a higher iduronidase levels (R2 =0.15, p=0.004) and lower DS/CS ratio (R2 =0.38, p=0.001). Improved ocular phenotypes in MPSI are associated with markers signifying efficacy of prior transplant. Early and effective HSCT may result in a better visual prognosis and reduction in ocular complications for patients with MPSI.