Stem Cell Infusion Adverse Reaction (SCIAR). a Review of Published Literature from Recent Years

Background:

SCIAR are often seen during transplants, but enough data are not available. In the past SCIAR were attributed to adverse event (AE) from DMSO. 

Objective:

To acquaint transplant infusionists with SCIAR causative factors and associated symptoms to guard for AE during infusion.

Method:

Study of published literature as available on PubMed website in the last 7 years.

Result:

11 articles by authors from diverse nations were reviewed. Only 1 publication is from USA. Reports are for autologous cryopreserved HPC-A (including few Allogeneic or marrow products). 3 studies reported SCIAR after DMSO wash. Data size is from 51- 952 infusions. AE ranges from 0.6 to 67%. Various symptoms are reported.

Systems	Symptoms
G-I	Nausea vomiting abdominal pain cramping
Respiratory	Cough dys/tachypnoea hypoxia SOB TRALI
Cardiac	Hypo/hypertension brady/tachycardia arrhythmia chest heaviness/pain MI cardiac arrest
Neuro	Amnesia seizure stroke numbness uc
Other	Fever chills flushing headache hypothermia anxiety vertigo allergy visual neuropathy back pain

Cause of SCIAR is either the graft (DMSO, cell content, volume, clumping) or the patient (age, gender, disease).

Article	Infusions	AE %	Finding/Symptoms	AE Cause	Suggestion/Conclusion
Feb 07 Donmez A, Turkey	194 Allo 25	25 0	Non cardiac > cardiac	Vol infused DMSO TNC	≤ 100 E+9 TNC
Apr 07 Wang JW, China	Ped 70	x	G-I	Single vol infusion	Fractionated infusion
Jun 07 Mueller LP, Germany	51	2	Cardiac ^DMSO	Neurotoxicity unrelated to DMSO vol	DMSO safe in Neurologic disease
Jul 07 Calmels B, France	490 (washed)	14	x	TNC	Improve Apheresis quality
Nov 07 Foïs E, France	952              (washed)	19	x	TNC Clumps	AE ^TNC
Dec 07 Cordoba R, Spain	144            (washed)	67	Allergic > G-I > Respiratory	Granulocyte  Clumping	≤ 6.065 E+9 Granulocytes
2007 Milone G, Italy	HPC-A 157  HPC-M 22	31 5	Cardiac ^Vol/Kg &  Inf  time Non cardiac ^Age & non-MNC	Age Non-MNC	≤ 5.0 E+8 Non-MNC
Jul 08 Bojanic I, Croatia	215	57	1 symptom 21% >1 36%	Female gender Multiple myeloma Granulocyte	AE ^Graft composition & disease
Jul 10 Curcioli AC, Brazil	114 Allo 47 Haplo 5	58	DMSO but not DMSO vol	DMSO	Good documentation required
Oct 10 Martìn-Henao GA, Spain	423	25	G-I Respiratory Seizure 0.7%	AE ^Granulocyte	x
Feb 12 Khera N, USA	(Comparative)       2006-07: 288  2008-09: 479	4  0.6	Infusions increased 4 fold	x	≤ 1.63 E+9 TNC/Kg/Day Multiple infusions

Discussion

Minor AE are attributed to DMSO, AE from washed cells to granulocyte or TNC content of graft. Cordoba R et al have reported 67% SCIAR despite DMSO wash. 7 years ago, Donmez A et al (Turkey) suggested restriction of infusion to <100 E+9 TNC; and Wang JW et al (China) advised fractionated infusions (vs. single infusion) in pediatric patients. Khera N et al (USA) have compared 2 groups over 2 years reporting 0.6% SCIAR on infusion of <1.63 E+9 TNC/Kg/day, fractionating infusions on different days.

Conclusion

Despite multiple variables, transplant centers can lower incidence of SCIAR by restricting graft dose.