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Journal of Neurorestoratology  2021, Vol. 9 Issue (2): 117-136    doi: 10.26599/JNR.2021.9040010
Research Article     
Improved survival in amyotrophic lateral sclerosis patients following autologous bone marrow mononuclear cell therapy: a long term 10-year retrospective study
Alok Sharma1,Hemangi Sane2,Amruta Paranjape2,3,(✉)(),Ritu Varghese2,Vivek Nair3,Hema Biju3,Dhanashree Sawant2,Nandini Gokulchandran1,Prerna Badhe4
1Department of Medical Services and Clinical Research, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
2Department of Research and Development, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
3Department of Neurorehabilitation, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
4Department of Regenerative Laboratory Services, NeuroGen Brain and Spine Institute, Navi Mumbai 400706, Maharashtra, India
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Abstract  Background:

Promising results from previous studies using cell therapy have paved the way for an innovative treatment option for amyotrophic lateral sclerosis (ALS). There is considerable evidence of immune and inflammatory abnormalities in ALS. Bone marrow mononuclear cells (BMMNCs) possess immunomodulatory properties and could contribute to slowing of disease progression.

Objective:

Aim of our study was to evaluate the long-term effect of autologous BMMNCs combined with standard treatment on survival duration in a large population and to evaluate effect of type of onset and hormonal status on survival duration in the intervention group.

Methods:

This controlled, retrospective study spanned over 10 years, 5 months; included 216 patients with probable or definite ALS, 150 in intervention group receiving autologous BMMNCs and standard treatment, and 66 in control group receiving only standard treatment. The estimated survival duration of control group and intervention group was computed and compared using Kaplan Meier analysis. Survival duration of patients with different types of onset and hormonal status was compared within the intervention group.

Results:

None of the patients reported any major adverse events related to cell administration or the procedure. Kaplan Meier analysis estimated survival duration in the intervention group to be 91.7 months while 49.7 months in the control group (p = 0.008). Within the intervention group, estimated survival was significantly higher (p = 0.013) in patients with limb onset (102.3 months) vs. bulbar onset (49.9 months); premenopausal women (93.1 months) vs. postmenopausal women (57.6 months) (p = 0.002); and preandropausal men (153.7 months) vs. postandropausal males (56.5 months) (p = 0.006).

Conclusion:

Cell therapy using autologous BMMNCs along with standard treatment offers a promising and safe option for ALS with the potential of long term beneficial effect and increased survival. Limb onset patients, premenopausal women and men ≤ 40 years of age demonstrated better treatment efficacy.



Key wordsautologous bone marrow mononuclear cells      cellular therapy      amyotrophic lateral sclerosis      motor neuron disease      pre-menopausal women      pre-andropausal men      cell therapy     
Received: 24 May 2021      Published: 19 October 2021
Corresponding Authors: Amruta Paranjape     E-mail: publications@neurogen.in
Cite this article:

Alok Sharma,Hemangi Sane,Amruta Paranjape,Ritu Varghese,Vivek Nair,Hema Biju,Dhanashree Sawant,Nandini Gokulchandran,Prerna Badhe. Improved survival in amyotrophic lateral sclerosis patients following autologous bone marrow mononuclear cell therapy: a long term 10-year retrospective study. Journal of Neurorestoratology, 2021, 9: 117-136.

URL:

http://jnr.tsinghuajournals.com/10.26599/JNR.2021.9040010     OR     http://jnr.tsinghuajournals.com/Y2021/V9/I2/117

Fig. 1Study protocol and outcome measures.
DemographicsIntervention groupControl group
Gender
No. of females (percentage)51 (34%)19 (28.79%)
No. of males (percentage)99 (66%)47 (71.21%)
Intramuscular Injection
Patients received intramuscular transplantation of cells (percentage)47 (31.3%)0 (0)
Patients not received intramuscular transplantation of cells (percentage)103 (68.7%)66 (100%)
Lithium
Patients prescribed lithium (percentage)125 (83.3%)0 (0)
Patients not prescribed lithium (percentage)25 (16.7%)66 (100%)
Edaravone
Edaravone taken (percentage)19 (12.7%)4 (6.01%)
Edaravone not taken (percentage)131 (87.3%)62 (93.94%)
Testosterone
Testosterone injection prescribed (percentage)23 (23.2%)0 (0)
Testosterone injection not prescribed (percentage)76 (76.8%)66 (100%)
Type of Onset
Patients with bulbar onset (percentage)34 (22.7%)16 (24.2%)
Patients with limb onset (percentage)116 (77.3%)50 (75.8%)
The average age at onset in years (SD)50 (10)54 (9)
Table 1Demographic data of the study population.
Adverse eventsPercentage adverse events immediately post-interventioncell-related adverse events
Minor
Spinal headache13.3 %None
Nausea and/or vomiting7.0 %
Pain at the aspiration site3.8 %
Backache/pain at the injection site10.1 %
Fatigue2.7 %
Constipation8.2 %
Loose motion1.9 %
Major
Sudden onset of respiratory discomfortNoneNone
Neurological deficitsNone
Paresthesia/loss of sensation in lower limbNone
Cardiac failureNone
Hematoma at the injection siteNone
Table 2Adverse events observed in the post-intervention period.
Premenopausal womenPostmenopausal womenPreandropausal menPostandropausal men
Distribution of mortality6 (5.9%)31 (30.4%)14 (13.7%)51 (50%)
Table 3Percentage distribution of deaths within intervention group in premenopausal and postmenopausal women, preandropausal and postandropausal men.
Intervention groupControl groupp value
Estimated survival duration (months)91.749.70.008*
Table 4Kaplan-Meier analysis of survival duration for patients with and without cell therapy.
Fig. 2Kaplan-Meier graph showing comparison of the estimated survival duration in intervention and control groups. Mean estimated survival duration was 91.7 months in the intervention group while in the control group it was 49.7 months (p = 0.008*). *Indicates a statistically significant difference between the groups.
Prognostic factorsEstimated survival duration (months) as calculated by Kaplan-Meier survival analysisStatistical significance
Onset type
Bulbar onset49.90.013*
Limb onset102.3
Hormonal status (Women)
Premenopausal women93.10.002*
Postmenopausal Women57.6
Hormonal status (Males)
Preandropausal men153.70.006*
Postandropausal men56.5
Table 5Effect of prognostic factors on survival duration within the intervention group.
Fig. 3Comparison of survival duration among the subgroups within the intervention group. (A) Bulbar onset vs. limb onset groups; (B) premenopausal vs. postmenopausal women; and (C) preandropausal vs. postandropausal men.
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