Autologous cell suspension grafting using ReCell in vitiligo and piebaldism patients: a randomized controlled pilot study

Vitiligo and piebaldism are cutaneous conditions associated with white patches
in patients. These depigmented lesions can be acquired (vitiligo) or congenital
(piebaldism). Vitiligo and piebaldism can alter a patients* appearance
dramatically and impair the patients* quality of life. In stable unresponsive
depigmented lesions autologous melanocyte transplantation is the treatment
option of choice. Various methods of autologous melanocyte transplantation have
been developed to treat stable unresponsive depigmented lesion. The basic
principle of all these surgical techniques is to transplant (autologous)
melanocytes from the normal pigmented skin to the depigmented macules where
melanocytes are absent.
Current treatment recommendations for choosing a transplantation method are
based on data from a limited number of studies, and on personal experience and
technical possibilities. Until recently, it was technically not possible to
treat patients with autologous epidermal cell suspension grafting in the NIPD.
Therefore, we routinely use the autologous punchgrafting technique as surgical
therapy. Punchgrafting shows good (more than 70 %) repigmentation in 68- 82 %
of the patients treated, although this technique is not suited for large
lesions. Long term follow-up studies on autologous cell suspension grafting,
suggest that it is an effective and safe method.19 Results of 52 treated
locations indicated a repigmentation rate of 95 % - 100% in segmental and
piebaldism patients and a rate of 49% in vitiligo vulgaris patients. One study
on five lesions that compared conventional melanocyte-keratinocyte
transplantation with ReCell concluded that there was no difference in the
efficacy and safety of both methods. ReCell showed to be a simple, safe and
effective method, although further research is required.
To date, only small series are published on the efficacy of ReCell in vitiligo.
A randomized controlled trial is not available yet.

The purpose of the present randomized controlled pilot study is to assess the
efficacy, safety and practical aspects of autologous epidermal cell suspension
grafting using ReCell in segmental vitiligo and piebaldism patients. Results of
this study may have an impact on our future practice in the treatment of
vitiligo and piebaldism.

The study will be a prospective single (observer) blinded randomized controlled
pilot study conducted at the Netherlands Institute for Pigment Disorders
(NIPD), Department of Dermatology, Academic Medical Centre, University of
Amsterdam, the Netherlands.
In each patient three (parts of) depigmented lesion(s) are randomly allocated
to receive one of the following regimes:

1) CO2 laser abrasion + ReCell epidermal skin graft suspension + UV-therapy
2) CO2 laser abrasion + UV-therapy
3) No treatment + UV-therapy

In each patient three (parts of) depigmented lesion(s) are randomly allocated
to receive one of the following regimes:

1) CO2 laser abrasion + ReCell epidermal skin graft suspension + UV-therapy
2) CO2 laser abrasion + UV-therapy
3) No treatment + UV-therapy

The donor site will be the hip region. Before treatment, the donor site will be
injected with a local anaesthetic: Lidocain 2 % . A split-thickness skin biopsy
of approximately 2x2 cm in area will be harvested at a depth of 0.15 to 0.2mm
with a dermatome. The skin biopsy that is obtained will be placed in the heated
enzyme solution in the device for a period of 15-20 minutes to allow cell
disaggregation. After 15-minutes, the skin biopsy will be removed from the
enzyme solution and a check takes place if scraping could be performed. If not,
the skin biopsy will be returned to the enzyme solution for a further 5-10
minutes before being tested again. When the test scrape is successful, the
biopsy will be dipped in the buffer solution to wash off any residual enzyme.
The biopsy will be scrapped to disaggregate the cells from the dermal epidermal
junction. The epidermal cells are then drawn up in a 5ml syringe and the
prepared suspension will be sprayed/ dripped on both the donor and the prepared
acceptor site.

Acceptor Site
Before treatment the acceptor site will be injected with a local anaesthetic of
Lidocain 2 %. According to current standard of care procedures the treatment
site will be superficially abraded using an ablative laser (10,600nm CO2 laser)
after which the prepared suspension will be sprayed on.

Control Site preparation
As control sites, 2 similar depigmented lesions will be used. One site will be
abraded using the same laser, and the same settings but will not receive an
epidermal suspension. The other site wll only receive UV- treatment.

Post-Operative Care
Oral antibiotics will be administered after the procedure .
The donor site, dermabraded control site and acceptor site wounds will be
covered with a non-adherent, low-absorbent, small-pore dressing (Telfa Clear*
Wound Dressing, Covidien). For recipient sites, a secondary dressing of greasy
gauze (e.g. Jelonet*) or saline soaked gauze is placed over the Telfa Clear
primary dressing. The Telfa Clear primary dressing should remain in situ for
6-8 days. Secondary dressings can be replaced as needed. At 6-8 days
post-treatment, the patient will return to the NIPD for dressing removal. Once
the primary dressing has been removed, a dressing according to standard NIPD
protocol will be applied to protect the wound surface, with or without an
adhesive retention dressing as clinically indicated.

Subjects participating in the study will not experience any delay or
disadvantage in the medical care of vitiligo as with such large lesions we
normally do not perform autologous transplantation. Consequently, patients who
participate in this study will not miss any regular treatment. Subjects
participating in the study will be requested to visit the NIPD (Amsterdam) once
to receive treatment, once for dressing removal and 2 times for evaluation and
follow-up.

Local side effects of the ReCell procedure for both donor site and acceptor
site are erythema (always 1-2 weeks), pain (often 1 day), itching (1-2 weeks),
burning sensation (often 1-3 days), local swelling (often 1-3 days), scar
formation (rare), hypo- and or hyper pigmentation (common). Infection in the
grafted area may occur but is very rare in our hands. No systemic side effects
are known for this treatment.
All outcome measures involve non-invasive procedures. Autologous epidermal cell
suspension grafting is a painful procedure that requires effective local
anesthesia.
All together the burden due to the study consists of treatment time, which will
be 2 hours and additional time investment of 3 visits to the NIPD consisting of
1 hour. Systemic side effects are not associated with any of the involved
treatments.
There will be a direct advantage for the patient as the treated area could show
repigmentation. In case of improvement of the depigmentation, the most
efficacious treatment can be utilized to treat the control sites of the
depigmented macule also.
Considering the lack of treatment options in these vitiligo depigmentations,
the balance between burden, possible side effects and prospect for improvement
is favorable. Results of this study may have an impact on our future practice
in the treatment of vitiligo and piebaldism.