Infusion-related side-effects in children undergoing autologous hematopoietic stem cell transplantation for acute leukemia

Perseghin, Paolo; Balduzzi, Adriana; Bonanomi, Sonia; Dassi, Maria; Buscemi, Filippo; Longoni, Daniela; Rovelli, Attilio; Uderzo, C

doi:10.1038/sj.bmt.1702462

Cited by 14 publications

(18 citation statements)

References 10 publications

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“…Infusion toxicity is reported in 26% to 70% of patients receiving cryopreserved, autologous peripheral blood HPCs . Factors associated with infusion toxicity include small size, multiple AHPCCs, total infusion volume, DMSO dose, mobilization with growth factor only, and a high prefreeze granulocyte count . Because most MC‐VCR patients required several AHPCCs, we reviewed the infusion and product records of chemotherapy‐mobilized patients to determine whether MC‐VCR was associated with increased infusion toxicity.…”

Section: Resultsmentioning

confidence: 99%

The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors

et al. 2014

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BACKGROUND Central nervous system (CNS) malignancies represent 20% of all childhood cancers. To improve outcomes in infants and children with high-risk disease, treatment can include adjuvant chemotherapy and early autologous peripheral blood human progenitor cell collection (AHPCC), followed by high-dose chemotherapy and stem cell rescue. In many protocols, postoperative chemotherapy includes the administration of weekly vincristine (VCR) between induction chemotherapy cycles, regardless of scheduled AHPCC. We observed anecdotal AHPCC failures in children receiving midcycle VCR (MC-VCR). STUDY DESIGN AND METHODS The study was an 8-year retrospective chart review of all children with a CNS malignancy and who underwent AHPCC. Information included patient demographic and clinical data, mobilization regimen, VCR administration, product yields, infusion toxicity, and patient charges. Data were analyzed relative to MC-VCR administration. Graphics and statistical analysis (t-test, chi-square, linear regression) were performed with commercial software. RESULTS Twenty-four patients and 47 AHPCCs were available for analysis. Nine patients (37%) received MC-VCR within 7 days of scheduled AHPCC. MC-VCR was associated with delayed marrow recovery (17.9 days vs. 14.9 days, p = 0.0012), decreased median peripheral CD34 counts (75 × 106 CD34/L vs. 352 × 106 CD34/L, p = 0.03), decreased median CD34 yields (2.4 × 106 CD34/L vs. 17.8 × 106 CD34/kg, p = 0.08), more AHPCCs per mobilization (2.9 vs. 1.1, p = 0.01), and an increased rate of remobilization (33% vs. 6%). Mean patient charges were 2.5× higher in patients receiving MC-VCR than controls (p = 0.01). CONCLUSION MC-VCR should be withheld before scheduled AHPCC to optimize CD34 collection.

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Section: Resultsmentioning

confidence: 99%

The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors

et al. 2014

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“…Double-unit grafts were used to augment engraftment 6–8 and potentially protect against relapse 9–13 . Twenty kilograms was set as the lower limit of recipient weight for administration of non-washed CB given the higher risk of dimethyl sulfoxide (DMSO) toxicity in smaller patients 14 . Furthermore, small pediatric patients may not tolerate large infusion volumes, and the potential cell loss with a wash has little impact on the infused total nucleated cell (TNC) dose in this group.…”

Section: Methodsmentioning

confidence: 99%

“No Wash” Albumin-Dextran Dilution for Double-Unit Cord Blood Transplantation is Safe with High Rates of Sustained Donor Engraftment

Dahi

Ponce

Devlin

et al. 2014

Biology of Blood and Marrow Transplantation

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Washing cord blood (CB) grafts involves product manipulation and may result in cell loss. We investigated double-unit CB transplantation (CBT) using red blood cell (RBC) depleted units diluted with albumin-dextran in patients with hematologic malignancies. One-hundred thirty-six patients [median 43 years (range 4–71) and 69 kilograms (kg) (range 24–111)] were transplanted with a 4–6/6 HLA-matched graft. Patients ≤ 20 kg were excluded as they only received washed units. Units were diluted a median of 8 fold to a median volume of 200 ml/unit. The median infused TNC doses were 2.7 (larger unit) and 2.0 (smaller unit) × 107/kg respectively, and the median post-thaw recovery was 86%. Units were infused consecutively (median 45 minutes/unit). While only 17 patients (13%) had no infusion reactions, reactions in the remaining 119 patients were almost exclusively mild-moderate (by CTCAE v4 criteria 12 grade 1, 43 grade 2, 63 grade 3) and only 1 patient (< 1%) had a severe (grade 4) reaction. Moreover, most were easily treated. Grade 2–3 hypertension was the most common in 101 (74%) patients. The cumulative incidence of sustained donor-derived neutrophil engraftment was high: 95% in myeloablative and 94% in non-myeloablative CBT recipients. With appropriate supportive care, double-unit CBT with RBC-depleted grafts infused after albumin-dextran dilution is safe with high rates of engraftment in patients > 20 kg.

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“…Cordoba et al found that, despite DMSO depletion and adequate histamine blockage, side effects continued to appear, suggested other factors such as number of granulocytes in the thawed product were more important than DMSO content, and perhaps removal of DMSO was not needed (4). However, most investigators believe removing DMSO before infusion is beneficial (2,3,5,8–11,13,15,18,20,36,52,56,59,62,64,69,73,74,104). In addition, most DMSO depletion strategies will also concomitantly remove cell debris and reduce neutrophil, platelet and other blood cell-derived soluble mediators, which may further contribute to decreasing the adverse event incidence and severity (2).…”

Section: Physiological Role Of Dmso In Adverse Reactionsmentioning

confidence: 99%

Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion

Shu

Heimfeld

Gao

2013

Bone Marrow Transplant

190

182

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Transplantation of hematopoietic stem cells (HSC) has been successfully developed as a part of treatment protocols for a large number of clinical indications, and cryopreservation of both autologous and allogeneic sources of HSC grafts is increasingly being employed to facilitate logistical challenges in coordinating the collection, processing, preparation, quality control testing and release of the final HSC product with delivery to the patient. Direct infusion of cryopreserved cell products into patients has been associated with the development of adverse reactions, ranging from relatively mild symptoms to much more serious, life-threatening complications, including allergic/gastrointestinal/cardiovascular/neurological complications, renal/hepatic dysfunctions, etc. In many cases the cryoprotective agent (CPA) used — which is typically dimethyl sulfoxide (DMSO), is believed to be the main causal agent of these adverse reactions and thus many studies recommend depletion of DMSO before cell infusion. In this paper, we will briefly review the history of HSC cryopreservation, the side effects reported after transplantation, along with advances in strategies for reducing the adverse reactions, including methods and devices for removal of DMSO. Strategies to minimize adverse effects include medication before and after transplantation, optimizing the infusion procedure, reducing the DMSO concentration or using alternative CPAs for cryopreservation, and removing DMSO prior to infusion. For DMSO removal, besides the traditional and widely applied method of centrifugation, new approaches have been explored in the last decade, such as filtration by spinning membrane, stepwise dilution-centrifugation using rotating syringe, diffusion-based DMSO extraction in microfluidic channels, dialysis and dilution-filtration through hollow-fiber dialyzers, and some instruments (CytoMate™, Sepax S-100, Cobe 2991, microfluidic channels, dilution-filtration system, etc.) as well. However, challenges still remain: development of the optimal (fast, safe, simple, automated, controllable, effective, and low-cost) methods and devices for CPA removal with minimum cell loss and damage remains an unfilled need.

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Infusion-related side-effects in children undergoing autologous hematopoietic stem cell transplantation for acute leukemia

Cited by 14 publications

References 10 publications

The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors

The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors

“No Wash” Albumin-Dextran Dilution for Double-Unit Cord Blood Transplantation is Safe with High Rates of Sustained Donor Engraftment

Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion

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