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Table 1 A summary of the clinical experience of MSCs in GVHD treatment

From: Clinical applications of mesenchymal stem cells

Year of publication

Patients (N)

MSC source

MSC dose

outcome

2007 [11]

6

haplo-identical family donors (n = 2), unrelated mismatched donors (n = 4)

1.0x10(6)/kg

Acute GVHD disappeared completely in five of six patients, four of whom are alive after a median follow-up of 40 months (range, 18–90 months) after the initiation of AMSC therapy. All four surviving patients are in good clinical condition and in remission of their hematological malignancy.

2008 [12]

55

HLA-identical sibling donors (n = 5), haploidentical donors (n = 18), third-party HLA-mismatched donors (n = 69).

1.4x10 (6) (min-max range 0.4-9x10 (6)) cells per kg

30 patients had a complete response and nine showed improvement. No patients had side-effects during or immediately after infusions of mesenchymal stem cells. Three patients had recurrent malignant disease and one developed de-novo acute myeloid leukaemia of recipient origin. Complete responders had lower transplantation-related mortality 1 year after infusion than did patients with partial or no response

2008 [13]

7

hematopoietic stem cell donors (n = 5), third party parental donor (n = 2)

From 0.4x10(6) to 3.0x10(6) per kg based on availability

One out of three patients showed slight improvement of chronic GVHD. Two patients with severe acute GVHD did not progress to cGVHD. One patient received MSC to stabilize graft function after secondary haploidentical transplantation. One patient recovered from trilineage failure due to severe hemophagocytosis.

2009[14]

13

Unrelated HLA disparate donors

A median dosage of 0.9 x 10(6)/kg (range 0.6-1.1).

Two patients (15%) responded and did not require any further escalation of immunosuppressive therapy. Eleven patients received additional salvage immunosuppressive therapy concomitant to further MSC transfusions, and after 28 days, five of them (45%) showed a response. Four patients (31%) are alive after a median follow-up of 257 days, including one patient who initially responded to MSC treatment.

2009 [15]

33

PBSCT combined with MSCs

From 0.5x10 (5) to 1.7x10(6) per kg

Fifteen patients (45.5%) developed grade I–IV acute GVHD (aGVHD) and only 2 (6.1%) developed grade III to IVaGVHD. Nine (31%) of 29 evaluable patients experienced chronic

GVHD (cGVHD).

2009 [16]

32

Unrelated, unmatched donor

2 or 8 million MSCs/kg in combination with corticosteroids

Ninety-four percent of patients had an initial response (77% complete response and 16% partial response). No infusional toxicities or ectopic tissue formations were reported.

2010 [17]

11

Unrelated HLA disparate donors

Median dose was 1.2 x 10(6)/kg (range: 0.7-3.7 x 10(6)/kg).

Overall response was 71.4%, with complete response in 23.8% of cases. None patients presented GVHD progression upon MSC administration, but 4 patients presented GVHD recurrence 2 to 5 months after infusion. Two patients developed chronic limited GVHD.

2011 [18]

12

premanufactured, universal donor

8 x 10(6)cells/kg in 2 patients and 2 x 10(6)cells/kg in the rest

7 (58%) patients had complete response, 2 (17%) partial response, and 3 (25%) mixed response. Complete resolution of GI symptoms occurred in 9 (75%) patients. The cumulative incidence of survival at 100 days from the initiation of therapy was 58%.