Incidence of thyroid dysfunction in children after HSCT with reduced intensity conditioning (RIC) or myeloablative conditioning (MAC)
Pediatric transplantation. 2021;:e13983
We have previously demonstrated a 11% incidence of post-transplant de novo thyroid disease, even with a radiation-free RIC regimen. Following the enactment of a universal late effects screening program at our institution, we compared the outcomes of 108 pediatric hematopoietic stem cell transplant recipients after a RIC regimen (n = 33) to those after a MAC regimen (n = 75) during the same time period. Overall, 10% of subjects developed thyroid dysfunction after HSCT, with a median follow-up of 669 days. Seven subjects had primary hypothyroidism prior to HSCT. Of the thirty-one subjects who received RIC, one (3.2%) developed a new thyroid disorder, compared to the nine of sixty-nine (13.0%) subjects who received MAC (p = .167). No significant associations were seen with donor type, graft-vs.-host disease, or total body irradiation. Nine of the 10 subjects who developed thyroid disease after transplant were asymptomatic. Continued follow-up of this contemporary cohort will further delineate risk factors for post-transplant-associated thyroid dysfunction and better inform discussions of transplant-associated sequelae.
Effect of Keratinocyte Growth Factor on Hospital Readmission and Regimen-Related Toxicities after Autologous Hematopoietic Cell Transplantation for Lymphoma
Transplantation and cellular therapy. 2021;27(2):179.e1-179.e4
Regimen-related toxicities with high-dose therapy followed by hematopoietic cell rescue leads to considerable patient distress, morbidity, and high readmission rates. Palifermin is a recombinant keratinocyte growth factor that is Food and Drug Administration-approved to decrease severe oral mucositis (OM) associated with autologous hematopoietic cell transplantation (ASCT) for hematologic malignancies. We added palifermin as a supportive care measure for patients with lymphoma undergoing ASCT with BEAM conditioning. We compared patients receiving palifermin (n?=?35) with historical controls (n?=?38) for toxicity and readmission outcomes. The cumulative incidence of OM of any grade was 23% in the palifermin-treated patients and 42% in the control group. Patients receiving palifermin were less likely to be readmitted (57% versus 82%; P?=?.04), had fewer hospital readmission days (median, 4 days versus 7 days; P < .01), and had fewer total days in the hospital through day +30 after ASCT (median, 12 days versus 15 days; P?=?.05). Fewer patients in the palifermin group had >20 days in the hospital through day +30 (9% in the palifermin group versus 23% of controls). Adverse events associated with palifermin were mild and transient. The addition of palifermin limits severe regimen-related toxicities and decreases readmissions and duration of hospital stay. This and other measures are needed to identify comprehensive and cost-effective approaches, possibly including palifermin, to prevent severe regimen-related toxicities and decrease health care resource utilization.
Veno-occlusive disease risk in pediatric patients with acute myeloid leukemia treated with gemtuzumab ozogamicin before allogeneic hematopoietic cell transplantation
Pediatric blood & cancer. 2021;:e29067
BACKGROUND Gemtuzumab ozogamicin (GO) administered before allogeneic hematopoietic cell transplantation (alloHCT) has been linked to an increased risk of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). PROCEDURE This retrospective analysis examined VOD/SOS risk and clinical outcomes in pediatric patients with acute myeloid leukemia who received myeloablative alloHCT in 2008-2011 with (n = 148) and without (n = 348; controls) prior GO exposure and were reported to the Center for International Blood and Marrow Transplant Research. RESULTS Cumulative incidences (95% confidence interval [CI]) of VOD/SOS and severe VOD/SOS, respectively, at 100 days were 16% (11-23%) and 8% (4-13%) for GO-exposed patients and 10% (7-13%) and 3% (2-5%) for controls. With a median follow-up of approximately 7 years, the 5-year adjusted overall survival probability (95% CI) after alloHCT was 51% (43-58%) and 55% (50-60%) for GO-exposed patients and controls, respectively; three (4%) and one (<1%) deaths were attributed to VOD/SOS. In multivariate analyses, GO exposure was observed to be associated with an increased risk of VOD/SOS at 100 days, but was not associated with overall survival, disease-free survival, relapse, or nonrelapse mortality. CONCLUSIONS Results suggest that GO treatment prior to alloHCT in pediatric patients may increase the risk of VOD/SOS but not death.
Evaluating the incidence of engraftment syndrome with different melphalan formulations in adult multiple myeloma and immunoglobulin light chain amyloidosis patients undergoing autologous hematopoietic cell transplantation
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2021;:1078155220987623
BACKGROUND Engraftment syndrome (ES) is a common complication of autologous hematopoietic cell transplantation (HCT). The difference in incidence of ES between melphalan formulations has not been widely reported throughout the literature and would allow for a more comprehensive understanding of the advantages and disadvantages of both melphalan formulations. PATIENTS AND METHODS This retrospective, single-center, observational study evaluated 83 adult multiple myeloma and immunoglobulin light chain amyloidosis patients who received either propylene glycol-containing (PG) or propylene glycol-free (PG-free) melphalan 140?mg/m(2) as single-agent conditioning chemotherapy for autologous HCT from May 31, 2015 to May 31, 2019. The primary outcome was to assess the incidence of ES, as defined using the Maiolino criteria, with both melphalan formulations. Secondary outcomes included an analysis of potential risk factors for the development of ES, as well as an evaluation of overall length of stay (LOS). RESULTS The incidence of ES for PG and PG-free melphalan did not differ significantly, 14/39 (35.9%) and 12/44 (27.3%) (P?=?0.4), respectively. No potential risk factors for ES were identified on multivariate logistic regression analysis. A statistically significant difference in number of days to engraftment was identified for PG and PG-free melphalan, 15.56 vs. 13.82?days (P?=?0.01), respectively; although, this did not translate to a decrease in LOS, 19.9 vs. 18.59?days (P?=?0.14). CONCLUSIONS The incidence of ES did not differ significantly between melphalan formulations. Future research is needed to determine whether the faster time to engraftment seen with PG-free melphalan may translate to a decrease in LOS.
Determining the incidence of interstitial pneumonitis and chronic kidney disease following full intensity haemopoetic stem cell transplant conditioned using a forward-planned intensity modulated total body irradiation technique
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2021
PURPOSE/OBJECTIVE Total body irradiation (TBI) remains a key component of conditioning for allogeneic haemopoietic stem cell transplant (HSCT), with interstitial pneumonitis (IP) and chronic kidney disease (CKD) important late sequelae. We undertook a retrospective service evaluation of TBI patients treated with a forward-planned intensity modulated radiotherapy technique (FP IMRT). MATERIAL/METHODS 74 adult patients were identified; all received step and shoot FP IMRT TBI, 14.4 Gy in 8 fractions over 4 days. Mean doses to the lungs and kidneys were 12- 12.5 Gy. Toxicities were defined as per CTCAE v4.0: IP as multilobar infiltrates on CT with symptoms of dyspnoea, and renal dysfunction as an Estimated Glomerular Filtration rate (eGFR) <60ml/min/1.73m(2) for >3 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), cumulative incidence of non-relapse mortality (NRM), relapse risk and of acute and chronic GvHD. RESULTS Patients received treatment for the following diagnosis: ALL/LBL (n=37); AML (n=33), CML-BC (n=2) and High grade NHL (n=2). The rate of IP due to any cause was 30%; positive microbiological evidence in 73% (16 /22). Idiopathic IP was seen in 8%, with only 4% (n=3) having IP Grade = 3. Two (4%) of 52 long term survivors developed CKD, one with thrombotic microangiopathy. 4 year NRM was 16% (CI 11-32%); no treatment related deaths in matched sibling or umbilical cord blood HSCT. CONCLUSION FP IMRT TBI, reducing dose to the lungs and kidneys, has lower rates of idiopathic IP and CKD compared to the literature. This technique is safe and effective conditioning for full intensity HSCT.
The use of low doses of methotrexate during peri-cell infusion period may be a risk factor for acute kidney injury in patients subjected to hematopoietic stem cell transplantation
Annals of hematology. 2020
Acute kidney injury (AKI) after hematopoietic stem cell transplantation (HSCT) is associated with high mortality rates. To determine the incidence and risk factors associated with AKI in patients undergoing HSCT during the infusion period, patients admitted for HSCT from 2012 to 2015 were studied. AKI was classified according to the KDIGO (Kidney Disease Improving Global Outcomes) criteria. We analyzed the main comorbidities, underlying conditions, types of transplant, preparative regimens, and use of potentially nephrotoxic drugs as risk factors for AKI. Among the 180 patients (median age 53 years), 69 (36.5%) developed AKI (23 KDIGO 1, 28 KDIGO 2, and 18 KDIGO 3), 49 (50.0%) undergoing allogeneic and 20 (22.3%) autologous transplantation, and 18 (9.4%) required dialysis. The main comorbidities were hypertension (38; 19.8%), and diabetes (19; 9.9%). The median pre-transplant creatinine was 0.7 mg/dl. Twenty-one patients died (10.9%). The risk factors for AKI in allogeneic HSCT were as follows: baseline estimated glomerular filtration rate (eGFR) (RR 1.12 (1.02-1.22), p = 0.019), use of vasopressors (RR 3.72 (2.20-6.29), p < 0.001), and use of methotrexate (RR 1.83 (1.08-3.11), p = 0.025). Male gender (RR 5.91 (1.65-21.16), p = 0.006), baseline eGFR (RR 1.22 (1.04-1.43), p = 0.011), and use of aminoglycosides (RR 3.92 (1.06-14.44), p = 0.041) were the risk factors for AKI associated with autologous HSCT. During hospitalization for HSCT, AKI was a common problem. The use of a low dose of methotrexate to prevent graft versus host disease was associated with its occurrence.
Oral levetiracetam for prevention of busulfan-induced seizures in adult hematopoietic cell transplant
International journal of clinical pharmacy. 2020
Background Antiseizure prophylaxis is recommended when high-dose of busulfan is given as part of the conditioning regimens in the allogenic hematopoietic stem cell transplant. Phenytoin has been widely used but its pharmacokinetics and pharmacodynamics profile makes its use complicated. Levetiracetam is a safe, effective and well tolerated antiseizure drug with good results in epileptic patients. Objective To describe our experience using oral (p.o) levetiracetam 1000 mg every 12 h (q12h) as an antiseizure prophylaxis, evaluating its preventive effects and adverse event rates after a high-dose of intravenous (i.v.) busulfan, as part of the conditioning regimen Methods Retrospective study of patients who underwent an allogenic hematopoietic stem cell transplant with a conditioning regimen based on high-dose of busulfan between January and November 2017. Results The study population comprised 36 patients, of whom 18 (50%) had acute myeloid leukemia as diagnosis. No seizures occurred in any patient. Levetiracetam was well tolerated and no serious adverse events were reported. Conclusions Our results suggest that giving levetiracetam at 1000 mg q12h p.o starting 12 h before the administration of i.v. busulfan until 48 h after the last dose, can be used as an alternative in the prevention of busulfan-induced seizures in adults.
Busulfan clearance does not predict the development of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation
International journal of hematology. 2020
Hepatic veno-occlusive disease (VOD) is a life-threatening complication following hematopoietic stem cell transplant (HSCT). Busulfan has a narrow therapeutic index and its concentration was found to correlate with VOD. Our primary objective was to assess the association between busulfan clearance and VOD in HSCT patients. In this retrospective analysis, we included patients who received their HSCT between 2003 and 2014 and followed at Sultan Qaboos University Hospital. All patients who received dose-targeted busulfan-containing conditioning were included. Target steady-state concentration (Css) was 800-900 ng/ml. VOD was assessed using modified Seattle criteria. The impact of busulfan clearance on VOD was analyzed using univariable logistic regression model. Seventy-three patients were included with a mean age of 15 years. Of those, 47% were transplanted for hematological malignancies and 53% for inherited hemoglobinopathies. Target Css was achieved in 85% of patients. The rate of VOD was 17%. There was no significant impact of busulfan clearance (p = 0.919) or area-under-the-concentration-time-curve (p = 0.275) on VOD. Targeting busulfan Css into narrow therapeutic range may have accounted for the findings. The risk of VOD might be related to other factors such as the genetic background, and more studies are required to investigate these factors.
Outpatient haploidentical hematopoietic stem cell transplant using post-transplant cyclophosphamide and incidence of hemorrhagic cystitis
Hematology, transfusion and cell therapy. 2020
INTRODUCTION Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. METHODS The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. RESULTS One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. CONCLUSIONS There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.
Acute toxicity and outcome among pediatric allogeneic hematopoietic transplant patients conditioned with treosulfan-based regimens
Pediatric hematology and oncology. 2020;:1-10
Treosulfan-based regimens constitute a feasible and increasingly used, but still myeloablative, conditioning in pediatric allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the acute toxicity and outcome of all consecutive (2004-2015) pediatric HSCT patients prepared for HSCT with treosulfan in a single-center setting. We included HSCTs performed for both nonmalignant (n = 23) and malignant diseases (n = 11). The controls were patients with nonmalignant diseases or hematological malignancies conditioned with cyclophosphamide (Cy)-total body irradiation (TBI)-based (39 patients) or busulfan-based regimens (11 patients). The major toxicities of the treosulfan-based regimens were limited to oral mucosa and skin. 50% of the patients needed IV morphine for severe mucositis compared to 31% in patients conditioned with Cy-TBI (P = 0.02). Other toxicities were rare. The disease-free survival (DFS) of patients transplanted for nonmalignant disorders was 88.9 +/- 7.5% at 2 years. The event-free survival (EFS) at 2 years in this small cohort for those with a malignant disease and a treosulfan-based conditioning was 54.5 +/- 1.5%. We conclude that a treosulfan-based conditioning regimen gives excellent DFS in pediatric HSCT performed for a nonmalignant disorder but with substantial mucosal toxicity. In a malignant disorder a treosulfan-based regimen looks promising but larger, preferably randomized, studies are needed to prove efficacy.