Early Morbimortality in Autologous Stem Cell Transplants Conducted on an Outpatient Basis in Persons with Autoimmune Disease: Experience in 1674 Patients

Background: Autologous hematopoietic stem cell transplantation (aHSCT) has been recognized as a valid therapeutic approach in persons with autoimmune disease because it may “reset” the immune response by abrogating autoreactive immune cells and exert other effects. Multiple sclerosis (MS) is the autoimmune disease that appears to most benefit from aHSCT, and the autoimmune condition in which the greatest experience with aHSCT has been gathered worldwide. We have been autografting persons with autoimmune disease since 2016 and have conducted 1674 aHSCT, following a conditioning regimen which is now called the “Mexican method”, endowed with a good safety profile.

Objective: To analyze the salient features of the outpatient conduction of aHSCT in the initial 28 days of the procedure in 1674 persons, while focusing on its early complications. The primary endpoint was early morbidity-free survival (MFS). Secondary endpoints were hospital admission, development of pneumothorax, hyponatremia, MS flare, or the development of neutropenic fever and overall survival (OS).

Method: Patients with autoimmune disease prospectively autografted in the HSCT-Mexico program, were included in the study. The transplant began on an outpatient basis in all cases, following the “Mexican Method”: conditioning was based on cyclophosphamide (200 mg/Kg, total dose), filgrastim, MESNA, and rituximab (1000 mg.). Prophylactic treatment with oral cotrimoxazole, acyclovir, and itraconazole was also administered. The protocol has been registered in ClinicalTrials.gov NCT02674217. Patients were admitted to the hospital if an acute complication developed. The Kolmogorov-Smirnov test was used and, since most of the parameters did not have a normal distribution, the Mann-Whitney U test was also necessary. Fisher's exact test was used, as needed.

Results: 1674 consecutive patients were analyzed; 1641 with MS, 29 with chronic inflammatory demyelinating neuropathy, and 4 with other autoimmune diseases. All 1674 aHSCT procedures were begun on an outpatient basis, and 1616 were completed outside the hospital (96%). Two patients died due to septicemia during the neutropenic nadir in the initial 30 days of the transplant; the causative agents were Klebsiella pneumoniae and Aeromonas veronii; one patient died due to pulmonary embolism. A central catheter was placed in 1607 cases (96%). In 12 persons (0.74%), a pneumothorax developed during the insertion of the catheter, and was resolved with a chest tube; these patients were admitted to the hospital and remained there for less than 48 hours. 126 persons (7.5%) developed neutropenic fever for more than 48 hours; in all instances, an oral quinolone was added to the prophylactic treatment, and 40 patients were admitted to the hospital to receive intravenous meropenem provided the quinolone did not resolve the fever. 21 patients (1.25%) developed hyponatremia and 2 were admitted to the hospital for intravenous fluid administration; the remaining cases were managed as outpatients. 45 patients had a MS flare, and warranted steroid treatment; 2 were admitted to the hospital. One patient developed reversible acute myocarditis and was also admitted to the hospital. The 30-day OS of the cohort was 99.8%, and the 30-day early morbimortality-free survival was 87.6%. The development of these early complications has decreased over time: The 30-day MFS has increased from 94.9% in the first 5 years to 98.2% in the last 5 years (p = 0.0003).

Conclusions: The “Mexican Method” followed to conduct aHSCT in persons with autoimmune disease is a safe procedure and transplants could be completed as outpatients in 96% of cases. The 30-day mortality was 0.17%, and the 30-day morbidity was 3.2%. Over time, these figures have decreased in our program, most likely reflecting a learning curve effect. Additional studies are needed to further analyze the safety of aHSCT when managing persons with autoimmune disease.

Gomez-Almaguer:Novartis: Consultancy, Other: Advisory board, Speakers Bureau; BMS: Consultancy, Other: Advisory board, Speakers Bureau; AbbVie: Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Advisory board, Speakers Bureau; Takeda: Consultancy, Other: Advisory board, Research Funding, Speakers Bureau; Tevas: Speakers Bureau; Seattle Genetics: Research Funding; Astex Pharmaceuticals: Research Funding; Blueprint Medicines: Research Funding; Kartos Therapeutics: Research Funding; Roche: Speakers Bureau; Sanofi: Speakers Bureau; Incyte: Research Funding; Amgen: Consultancy, Other: Advisory board, Research Funding, Speakers Bureau; Gilead/Forty Seven: Research Funding; ConstellationPharmaceuticals: Research Funding. Gomez-De Leon:Abbvie: Honoraria; Amgen: Honoraria; bms: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Sanofi: Honoraria, Other: Advisory board; Janssen: Other: Advisory board.