Bone Marrow Transplantation (2012) 47, 1368 - 1369
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LETTER TO THE EDITOR
Successful treatment of a refractory skin ulcer in chronic
cutaneous GvHD after allogeneic HSCT with split-thickness
skin allografting from the stem cell donor
A 29-year-old woman was diagnosed with Flt-3-positive AML. In
August 2004, she received allogeneic HSCT from her HLA-identical
sister after a myeloablative-conditioning regimen. CsA and MTX
were used for GvHD prophylaxis.
One month after the engraftment and achievement of
complete donor chimerism, the patient developed a steroidrefractory acute GvHD (grade IV) of liver and gut, which was
successfully treated with sequential combinations of different
immunosuppressive drugs (prednisolone, tacrolimus, etanercept,
daclizumab, ATG and MMF), resulting in remission of GVHD. In
June 2005, immunosuppression could be tapered and stopped.
In September 2005, chronic cutaneous GvHD was diagnosed
and initially treated with topical steroids. During the following
2 months, GvHD progressed, involving the whole integument in a
lichenoid and sclerodermiform manner, requiring again systemic
immunosuppression with prednisolone and tacrolimus. Despite
different treatment lines with rituximab, MMF, everolimus and
MTX, the therapy-refractory cutaneous GvHD further progressed,
resulting in extensive ulceration of the scalp (12 17 cm) until
June 2008 (Figure 1). As conservative treatment did not result in
re-epithelialisation and was complicated by secondary infections,
we performed a split-thickness skin grafting.
To avoid reactivation of GvHD, we decided to use an allogeneic
skin graft from her HLA-identical sister. The first step of
reconstitution consisted of wound debridement and a first
meshed skin graft covering nearly 100% of the ulcerated area
under continuous immunosuppression with prednisolone, MMF
and MTX. Skin grafts were taken from the donor thigh under local
anaesthesia by using an electric dermatome with a common cut
depth of 0.3 mm. Grafts were applied after meshing to 1.5 times
immediately to the ulcer base and secured with surgical staples at
the wound edge. After 3 months, 50% of the wound area was
covered by engrafted donor skin. After further wound debridement, the remaining ulcerated area was covered by a second step
of split-thickness skin transplantation. This procedure resulted
in complete healing of the large ulceration within 5 months
(Figure 2). Interestingly, we were able to gradually taper systemic
immunosuppression from prednisolone, MMF and MTX to MMF
alone, without local or systemic deterioration of GvHD. Immunosuppression could be stopped completely in December 2010. The
patient remains in CR concerning AML with complete donor
chimerism and is full-time working without any symptoms of
chronic GvHD.
In cases of skin ulceration due to chronic cutaneous GvHD after
allogeneic HSCT, there are only a few reports in the current
literature about treatment with skin transplantation. One of the
earliest reports on treatment of ulcerating chronic GvHD with skin
grafts from the BM donor was published by Knobler et al.1 in 1985.
Three further groups reported on successful allogeneic skin
grafting in severe chronic GvHD from the HLA-identical stem cell
donor.2 - 4 Recent data come from French colleagues who treated
a patient for extensive-ulcerating cutaneous GvHD, with a twostep skin transplantation of the HLA-identical sister resulting in
complete coverage of the skin lesion and subsequent withdrawal
of immunosuppression.5 Berg et al.6 treated another female
patient after allogeneic HSCT with severe cutaneous chronic GvHD
of the scalp, with split-thickness skin transplantation of the HLAidentical sibling stem-cell donor under low-dose immunosuppression with prednisolone, resulting in complete engraftment of
the graft.
Successful skin grafting from the stem-cell donor is of
immunological interest. First, it clearly demonstrates that chronic
GvHD is still a continuing alloreaction against recipient Ags, as
dermal Ags are present in both donor and recipient skin. Second,
our observations indicate not only absence of GvHD in the grafted
skin, but suggest an additional immunomodulatory effect. The
ability to taper systemic immunosuppression after skin grafting is
compatible with potential induction of tolerance by migratory
Figure 1. Ulcerating chronic GvHD of the scalp (12 17 cm) after
allogeneic HSCT.
Figure 2. Five months after two split-thickness skin transplantations
of the HLA-identical donor.
Bone Marrow Transplantation (2012) 47, 1368 -- 1369; doi:10.1038/
bmt.2012.16; published online 20 February 2012
Letter to the Editor
cells of the skin graft. This is in line with murine data, suggesting
immunomodulating property via DCs in skin, which could lead to
induction of regulatory T cells.7,8
In conclusion, we could show that in a case of treatmentrefractory, ulcerating chronic GvHD after allogeneic HSCT, splitthickness skin transplantation from the HLA-identical donor can
be a successful permanent treatment option. Whether donor skin
grafts exert a systemic immunomodulating effect remains
speculative and needs further investigation.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
J Ammer1, L Prantl2, B Holler1, K Landfried1, D Wolff1,
S Karrer3, R Andreesen1 and E Holler1
1
Department of Haematology and Oncology, University Hospital
Regensburg, Regensburg, Germany;
2
Center of Plastical and Reconstructive Surgery, University Hospital
Regensburg, Regensburg, Germany and
3
Department of Dermatology, University Hospital Regensburg,
Regensburg, Germany
E-mail: [email protected]
& 2012 Macmillan Publishers Limited
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