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Ovarian tissue cryopreservation for fertility preservation before hematopoietic stem cell transplantation in patients with sickle cell disease: safety, ovarian function follow-up, and results of ovarian tissue transplantation
Missontsa, M. M., Bernaudin, F., Fortin, A., Dhédin, N., Pondarré, C., Yakouben, K., Neven, B., Castelle, M., Cavazzana, M., Lezeau, H., et al
Journal of assisted reproduction and genetics. 2024
Abstract
PURPOSE To describe the experience of performing ovarian tissue cryopreservation (OTC) before hematopoietic stem cell transplantation (HSCT), among girls/women with severe sickle cell disease (SCD)(SS or S/β(0)-thalassemia) who are, besides the usual surgical risk, at risk of SCD-related complications during the fertility preservation procedure for improving their counseling and management. METHODS This retrospective study included 75 patients (girls/women) with SCD who have had OTC before myeloablative conditioning regimen (MAC) for HSCT. Characteristics of patients and data on OTC, ovarian status follow-up, and results of ovarian tissue transplantation (OTT) were collected in medical records. RESULTS At OTC, the median (IQR 25-75; range) age of the patients was 9.6 (6.9-14.1; 3.6-28.3) years, 56/75 were prepubertal, and no SCD or surgery-related complications occurred. The median follow-up post-HSCT was > 9 years. At the last follow-up, among prepubertal patients at HSCT, 26/56 were ≥ 15 years old and presented with a premature ovarian insufficiency (POI), except 2, including the patient who had received an OTT to induce puberty. Eight were 13-15 years old and presented for POI. The remaining 22 patients were under 13. Among the 19 patients who were menarche at HSCT, 2 died 6 months post-HSCT and we do not have ovarian function follow-up for the other 2 patients. All the remaining patients (n = 15) had POI. Five patients had OTT. All had a return of ovarian function. One patient gave birth to a healthy baby. CONCLUSION OTC is a safe fertility preservation technique and could be offered before MAC independent of the patient's age.
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Long-term parental distress after pediatric hematopoietic stem cell transplantation for nonmalignant diseases
Bense, J. E., Stiggelbout, A. M., Lankester, A. C., de Pagter, A. P. J.
Pediatric blood & cancer. 2023;:e30638
Abstract
BACKGROUND Survival rates have continued to increase for pediatric hematopoietic stem cell transplantation (HSCT) for nonmalignant diseases. Despite the crucial role of caregivers in this high-intensity treatment, knowledge about long-term parental impact is lacking. PROCEDURE This cross-sectional study assessed parental distress and everyday problems in parents of patients 2 years and older after pediatric HSCT for a nonmalignant disease using Distress Thermometer for Parents (DT-P), and compared outcomes to matched Dutch parents of healthy children and Dutch parents of children with a chronic condition (CC). RESULTS Median follow-up was 5.3 years (interquartile range [IQR]: 2.9-8.6). Underlying diseases were inborn errors of immunity (N = 30), hemoglobinopathies (N = 13), and bone marrow failure (N = 27). Mothers of pediatric HSCT recipients (N = 70) reported comparable overall distress levels to mothers of healthy children, but experienced more distress related to parenting problems, specifically managing their child's emotions, discussing disease consequences, and fostering independence. Fathers of HSCT recipients (N = 45) reported higher overall distress levels and had more emotional distress compared to fathers of healthy children. CONCLUSIONS Overall, parental distress and everyday problems of parents of HSCT recipients are comparable to those of parents of children with CC. However, there is ongoing parental burden, both emotional and in parenting, long-term after HSCT compared to parents of healthy children, and the type of burden differs between mothers and fathers. These results indicate that individualized parental supportive care should not remain restricted to the acute hospitalization phase, but also be actively offered during long-term follow-up after pediatric HSCT.
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3.
Hoping for a normal life: Decision-making on hematopoietic stem cell transplantation by patients with a hemoglobinopathy and their caregivers
Mekelenkamp, H., de Vries, M., Saalmink, I., Nur, E., Kerkhoffs, J. L., Heijboer, H., Cnossen, M., Lankester, A., Smiers, F.
Pediatric blood & cancer. 2023;:e30808
Abstract
BACKGROUND To provide insight into the perspectives of children and young adults with transfusion-dependent thalassemia and sickle cell disease and their caregivers regarding the decision for hematopoietic stem cell transplantation (HSCT). PROCEDURE A qualitative longitudinal multicenter study. Data collection consisted of 40 audio-recorded conversations between physicians and families and 77 interviews with patients and/or caregivers related to 27 unique cases, collected at different time points throughout the decision-making process. RESULTS Conversations and interviews revealed "hoping for a normal life" as an overarching theme, consisting of four main topics: (i) "Building a frame of reference" refers to a process where patients or families try to obtain comprehensive information on HSCT and translate this to their situation to decide. (ii) "Balancing between loss and benefit" reports the process of considering the advantages and disadvantages of continuing with supportive care to treat their disease versus choosing HSCT. (iii) "Experiencing the impact of HSCT" describes the impactfull experience of the HSCT period by those who chose HSCT. (iv) "Balancing again" refers to reflecting on the decision made. CONCLUSIONS The hope for a normal life guided the decision-making process, described as a constant balance between the impact of the disease and HSCT. A structured approach to explore patients' and caregivers' perspectives on HSCT decision-making is needed, where specifically discussing the impact of the disease and hope for a normal life need to be integrated in the process.
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Pre-transplantation vitamin D deficiency increases acute graft-versus-host disease after hematopoietic stem cell transplantation in Thalassemia Major patients
Daloğlu, H., Uygun, V., Öztürkmen, S., Yalçın, K., Karasu, G., Yeşilipek, A.
Clinical transplantation. 2022;:e14874
Abstract
Although there are many studies on the role of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT), outcomes have often reported conflicting results because of the heterogeneity of the patients in the studies. We investigated the association between VDD prior to HSCT and outcomes after HSCT in a relatively homogenous group of patients with thalassemia major (TM) who received identical treatment for TM before transplantation, and the same conditioning regimen and GVHD prophylaxis during and after transplantation. All patients, including the patients with normal vitamin D 3 levels received 400 to 800 IU per day of vitamin D for the first six months after HSCT. Pre-HSCT VDD increased the frequency of aGVHD after transplantation, particularly in HSCTs performed with PBSC for the stem cell source. Pre-transplant low vitamin D 3 levels had no association with transplant outcomes such as engraftment, viral infections, alloimmunization, chronic GvHD, total days of hospitalization, and success in terms of transfusion independence. Low vitamin D 3 levels before HSCT carry a significant risk for aGVHD. All patients with TM should be screened for VDD before HSCT, and every effort should be made to supplement vitamin D before the transplant in VDD patients. This article is protected by copyright. All rights reserved.
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5.
Frontline-matched sibling donor transplant of aplastic anemia patients using primed versus steady-state bone marrow grafts
El Fakih, R., Alfraih, F., Alhayli, S., Ahmed, S. O., Shaheen, M., Chaudhri, N., Alsharif, F., Hanbali, A., Alshaibani, A., Alotaibi, A. S., et al
Annals of hematology. 2021
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Full text
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Editor's Choice
Abstract
Priming donors with G-CSF before BM harvest is reported to improve engraftment and GvHD in recipients. These effects are highly desirable when transplanting patients with non-neoplastic hematologic diseases, particularly AA patients. Here we retrospectively report the outcomes of 39 AA patients receiving a primed BM graft from MSD to 43 patients receiving a steady-state BM graft from MSD, otherwise transplanted using a uniform transplant platform. The graft had higher TNC and CD34 cell concentrations in the primed group (p?0.001), and that was reflected in higher TNC and CD34 doses per kilogram of recipient in the primed group (p?=?0.004 and 0.03, respectively). The OS for primed BM graft recipients was 97.4% and 78.9% for the steady-state BM graft recipients, p-value?=?0.01. The cumulative incidence of death without GF was 2.6% in the primed group and 16.3% in the steady-state group, p-value?=?0.03. There was no difference in GvHD incidence between the two groups. We confirm that priming improved the TNC and CD34 graft concentration and cell dose; this evidence along with other reported studies constitute reasonable evidence to prove that BM priming improve engraftment. We observed no increase in GvHD using primed BM graft.
PICO Summary
Population
Patients with aplastic anaemia, undergoing matched sibling donor transplant (n=82)
Intervention
Bone marrow (BM) graft primed with G-CSF before bone marrow harvest (n=39)
Comparison
Steady state BM graft (n=43)
Outcome
The graft had higher TNC and CD34 cell concentrations in the primed group, and that was reflected in higher TNC and CD34 doses per kilogram of recipient in the primed group. The overall survival for primed BM graft recipients was 97.4% and 78.9% for the steady-state BM graft recipients. The cumulative incidence of death without graft failure was 2.6% in the primed group and 16.3% in the steady-state group. There was no difference in GvHD incidence between the two groups.
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Granulocyte Colony-Stimulating Factor is Safe and Well Tolerated following Allogeneic Transplantation in Patients with Sickle Cell Disease
Shah, N. C., Bhoopatiraju, S., Abraham, A., Anderson, E., Andreansky, M., Bhatia, M., Chaudhury, S., Cuvelier, G. D. E., Godder, K., Grimley, M., et al
Transplantation and cellular therapy. 2021
Abstract
Granulocyte colony-stimulating factor (G-CSF) used after hematopoietic stem cell transplantation (HSCT) can enhance neutrophil recovery in patients rendered neutropenic by the preparative regimen. G-CSF is contraindicated in patients with sickle cell disease (SCD) as life-threatening complications can ensue in the presence of sickle vasculopathy. However, the safety profile of G-CSF after HSCT for SCD has not been previously described. We report clinical outcomes in the first 100 days post-HSCT in patients supported with G-CSF until neutrophil recovery on a clinical trial of reduced intensity transplantation for SCD. Patients (n=62) received G-CSF for a median of 9 days (range, 5-33) following transplant from the best available stem cell source. Preparation for transplant included a target hemoglobin S level of ≤45%. Neutrophil engraftment (ANC >0.5 × 10(3)/mL) was achieved at a median of 13 days (range,10-34) and platelet engraftment (>50 × 10(3)/mL) at a median of 19 days (range, 12-71). The median duration of inpatient hospitalization following stem cell infusion (day 0) was 21.5 days (range 11-33). No patient developed SCD related complications following G-CSF use. The most common organ toxicities encountered between G-CSF commencement (on day +7) and day +100 were anorexia (14), hypertension (11) and electrolyte imbalance requiring correction (9). Central nervous system related events were noted in 5 patients, all with pre-existing cerebral vasculopathy/moyamoya disease and attributed to reversible posterior leukoencephalopathy syndrome (RPLS) in the presence of calcineurin inhibitor therapy and hypertension. We conclude that G-CSF does not adversely impact SCD transplant recipients and can be safely used post-HSCT to enhance neutrophil recovery.
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Assessment of Activity of Daily Life in Mucopolysaccharidosis Type II Patients with Hematopoietic Stem Cell Transplantation
Suzuki, Y., Taylor, M., Orii, K., Fukao, T., Orii, T., Tomatsu, S.
Diagnostics (Basel, Switzerland). 2020;10(1)
Abstract
The effectiveness of hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis type II (MPS II, Hunter disease) remains controversial although recent studies have shown HSCT provides more clinical impact. This study aims to evaluate the long-term effectiveness of HSCT using the activity of daily living (ADL) scores in patients with MPS II. Sixty-nine severely affected MPS II patients (19 patients who received HSCT and 50 untreated patients) and 40 attenuated affected patients (five with HSCT and 35 untreated) were investigated by a simplified ADL questionnaire. The frequency of clinical findings and the scores of ADL (verbal, gross motor, and the level of care) were analyzed statistically. The mean age of onset of 19 severely affected patients who received HSCT was 1.40 years +/- 1.06, which is not statistically different from that of 50 untreated patients (p = 0.11). Macroglossia, frequent airway infection, hepatosplenomegaly, joint contracture, and sleep apnea were less frequent in the HSCT-treated group of severe MPS II patients. The severe phenotype HSCT treated group reported a statistically significant higher score of verbal function and gross motor function between the ages of 10 and 15 years and a higher level of care score between 10 and 20 years. Patients with the attenuated phenotype showed high ADL scores, and all of five HSCT treated patients reported a lower frequency of frequent airway infection, coarse skin, umbilical/inguinal hernia, hepatosplenomegaly, heart valve disorders, and carpal tunnel. In conclusion, HSCT is effective, resulting in improvements in clinical features and ADL in patients with MPS II. HSCT should be re-reviewed as a therapeutic option for MPS II patients.
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Safety of tunneled central venous catheters in pediatric hematopoietic stem cell recipients with severe primary immunodeficiency diseases
Martynov, I., Klima-Frysch, J., Kluwe, W., Engel, C., Schoenberger, J.
PloS one. 2020;15(5):e0233016
Abstract
Tunneled central venous catheters (TCVCs) provide prolonged intravenous access for pediatric patients with severe primary immunodeficiency disease (PID) undergoing hematopoietic stem cell transplantation (HSCT). However, little is known about the epidemiology and clinical significance of TCVC-related morbidity in this particular patient group. We conducted the retrospective analysis of patients with severe PID who received percutaneous landmark-guided TCVC implantation prior to HSCT. We analyzed 92 consecutive TCVC implantations in 69 patients (median [interquartile range] age 3.0 [0-11] years) with severe combined immune deficiency (n = 39, 42.4%), chronic granulomatous disease (n = 17, 18.4%), and other rare PID syndromes (n = 36, 39.2%). The median length of TCVC observation was 144.1 (85.5-194.6) days with a total of 14,040 catheter days at risk (cdr). The overall rate of adverse events during catheter insertion was 17.4% (n = 16) and 25.0% during catheter dwell period (n = 23, catheter risk [CR] per 1000 cdr = 1.64). The most common complication was TCVC-related infection with an overall prevalence of 9.8% (n = 9, CR = 0.64), followed by late dislocation (n = 6, 6.5%, CR = 0.43), early dislocation (n = 4, 4.3%) and catheter dysfunction (n = 4, 4.3%, CR = 0.28). TCVCs are safe in children with severe PID undergoing HSCT with relatively low rates of TCVC-related infection.
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Sleep disturbance in adults with sickle cell disease: relationships with executive and psychological functioning
Rhodes, A., Martin, S., Wolters, P., Rodriguez, Y., Toledo-Tamula, M. A., Struemph, K., Fitzhugh, C., Hsieh, M., Tisdale, J.
Annals of hematology. 2020
Abstract
Sleep disturbance is common among children with sickle cell disease (SCD) and is related to neurocognitive difficulties. However, research on sleep disturbances and related variables among adults with SCD is extremely limited. The present study examined the relationship between sleep, executive functioning, and emotional functioning among 62 adults (29 females; M age = 32 years, SD = 7.79) with SCD preparing to undergo a stem cell transplant. Participants were administered a neurocognitive evaluation that included objective and subjective measures of executive functioning, and they completed PROMIS self-report measures of anxiety, depression, and pain intensity. Results showed that about 17% of participants endorsed clinically significant sleep disruptions, while 16.1% and 8% endorsed clinically significant symptoms of anxiety and depression, respectively. Sleep disturbance in these adults was not significantly correlated with objective or subjective measures of executive functioning. Moreover, anxiety, but not depression, was a significant mediator between self-reported sleep difficulties and both objective and subjective measures of executive functioning while controlling for pain intensity. Future research on sleep interventions will be essential for ameliorating the effects of sleep disturbance on executive functioning and anxiety among adults with SCD.
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An online survey on burden of illness among families with post-stem cell transplant mucopolysaccharidosis type I children in the United States
Conner, T., Cook, F., Fernandez, V., Rascati, K., Rangel-Miller, V.
Orphanet journal of rare diseases. 2019;14(1):48
Abstract
BACKGROUND Severe mucopolysaccharidosis type I (also known as Hurler syndrome) is a rare devasting recessive genetic disease caused by the deficiency of an enzyme. Hematopoietic stem cell transplant is the standard of care in the United States, usually conducted before the child is 3 years of age, but little is known about the continued medical and educational needs of the child after transplant. A greater understanding of the burden of illness on the primary caregiver is also needed. Therefore, this online survey sought to gather information on the burden of severe MPS I in the United States at least 1 year after transplant. RESULTS Thirty-two respondents reported that children with severe MPS I have significant medical and educational needs after transplant. Healthcare resource use was frequent, especially in the outpatient setting specifically for bone, cardiac, and vision complications that were not relieved by HSCT. Twenty-five percent of the children had been hospitalized at least once in the last year and two had been hospitalized twice. The most common reasons for overnight hospitalizations included orthopedic surgeries and respiratory infections. Among children ages 5 and older, only 3 of 28 (11%) were able to attend school with no special support. While caregivers were generally satisfied with the healthcare services their child receives, 69% of working caregivers reported negative impact on their ability to conduct work tasks, and 54% of caregivers did not work so that they could care for the child. CONCLUSIONS Results suggest that severe MPS I children continue to require medical care and special support for education. Future research on the burden of illness on families affected by severe MPS I is needed to better understand total cost of care, and to identify therapies and interventions that reduce burden of illness. Future studies that compare cost of and access to health care in different countries may provide a more global view of the burden of MPS I.