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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3098-3104
Successful Use of Extracorporeal Photochemotherapy in the Treatment
of Severe Acute and Chronic Graft-Versus-Host Disease
By
Hildegard T. Greinix,
Beatrix Volc-Platzer,
Werner Rabitsch,
Bernd Gmeinhart,
Carlos Guevara-Pineda,
Peter Kalhs,
Jean Krutmann,
Herbert Hönigsmann,
Marina Ciovica, and
Robert M. Knobler
From the Department of Medicine I, Bone Marrow Transplantation Unit,
the Department of Dermatology, Division of Immunology, Allergy and
Infectious Diseases, and the Department of Dermatology, Division of
Special and Environmental Dermatology, University of Vienna, Vienna,
Austria; and the Department of Dermatology, Division of Clinical and
Experimental Dermatology, Heinrich-Heine-University of Duesseldorf,
Duesseldorf, Germany.
 |
ABSTRACT |
Extracorporeal exposure of peripheral blood mononuclear cells to the
photosensitizing compound 8-methoxypsoralen and ultraviolet A radiation
has been shown to be effective in the treatment of several
T-cell-mediated diseases, including cutaneous T-cell lymphoma and
rejection after organ transplantation. We present 21 patients (10 men
and 11 women) with hematological malignancies with a median age of 36 years (range, 25 to 55 years) who had received marrow grafts from
sibling (n = 12) or unrelated (n = 9) donors. Six patients had
acute graft-versus-host disease (GVHD) grade II to III not responding
to cyclosporine A (CSA) and prednisolone when referred to
extracorporeal photochemotherapy (ECP). In 15 patients, 2 to 24 months
after bone marrow transplantation (BMT), extensive chronic GVHD with
involvement of skin (n = 15), liver (n = 10), oral mucosa
(n = 11), ocular glands (n = 6), and thrombocytopenia (n = 3)
developed and was unresponsive to conventional therapy, including
steroids. All patients were treated with ECP on 2 consecutive days
every 2 weeks for the first 3 months and thereafter every 4 weeks until
resolution of GVHD. ECP was tolerated excellently without any
significant side effects. After a median of 14 cycles of ECP, acute
GVHD resolved completely in 4 of 6 patients (67%) and partially in
another 2 patients. Cutaneous chronic GVHD completely resolved in 12 of
15 (80%) patients. Contractures of knees and elbows due to scleroderma
resolved partially. Oral mucosal ulcerations resolved in all patients.
Seven of 10 patients (70%) with liver involvement had complete
responses after ECP. After discontinuation of ECP, no severe infections
were observed. Our findings suggest that ECP is a safe and effective
adjunct therapy for both acute and extensive chronic GVHD with skin and
visceral involvement and resistance to conventional therapy.
© 1998 by The American Society of Hematology.
| |
INTRODUCTION |
DESPITE IMPROVEMENTS in posttransplant
immunosuppression, up to 30% of HLA-identical marrow graft recipients
and up to 90% of patients receiving marrow from unrelated donors still
develop significant acute graft-versus-host disease
(GVHD).1-3 Prednisone has been shown to be effective in the
treatment of established acute GVHD.4 However, patients not
responding to corticosteroids are at high risk of death due to
infections. Chronic GVHD affects 50% of long-term marrow transplant
survivors and is lethal in 20% to 40% of affected patients, despite
aggressive treatment.1,5 Primary therapy for extensive
chronic GVHD includes corticosteroids and cyclosporine A
(CSA).6 Other therapeutic options are thalidomide, azathioprine, psoralen and ultraviolet A (PUVA), and monoclonal antibodies.1,7,8 However, these therapies are often
unsuccessful in patients with extensive multiorgan involvement and are
associated with significant therapy-related complications. Considering
the toxicity and incomplete response rates of conventional treatment for chronic GVHD, alternative approaches are needed for patients who do
not respond to first-line therapy.
Extracorporeal photochemotherapy (ECP) is currently being used for the
treatment of cutaneous T-cell lymphoma, selected autoimmune diseases,
and rejection after organ transplantation.9-12 ECP consists of infusion of UVA irradiated autologous peripheral blood mononuclear cells collected by apheresis and incubated with 8-methoxypsoralen (8-MOP). Recently, ECP has been used in treatment of severe
GVHD.13-15
We present here our experience in patients with extensive chronic and
steroid-refractory severe acute GVHD treated with ECP.
| |
MATERIALS AND METHODS |
Patients.
Twenty-one patients (10 men and 11 women; median age, 36 years; range,
25 to 55 years) underwent allogeneic marrow transplantation for acute
myeloid leukemia (n = 5), acute lymphoblastic leukemia (n = 4), chronic
myeloid leukemia (n = 8), non-Hodgkin's lymphoma (n = 3), or severe
aplastic anemia (n = 1). Their pretransplant characteristics are shown
in Table 1. All were conditioned for transplantation with cyclophosphamide (CY) and fractionated total body
irradiation (TBI); etoposide was also administered in 3 patients.
Marrow donors were HLA-identical siblings in 12 patients, HLA-identical
unrelated donors in 6 patients, and 1-antigen mismatched unrelated
donors in 3 patients. Bone marrow (BM) was harvested and infused as
previously described.16 For GVHD prophylaxis, 17 patients
received CSA and methotrexate (MTX) according to the Seattle
protocol,2 3 patients received CSA only,2 and 1 patient received CSA and prednisolone.17 Patients were
hospitalized in isolation rooms with laminar air-flow or reverse
isolation. They received antimicrobial prophylaxis with nonabsorbable
antibiotics and Pneumocystis carinii prophylaxis with
cotrimoxazole. For cytomegalovirus (CMV)-prophylaxis, patients received
acyclovir as described.18 Packed red blood cells (RBCs)
were administered to maintain hemoglobin concentrations greater than
8.0 g/dL and platelet transfusions were administered to keep the
platelet count greater than 20 × 109/L. All patients
received CMV-negative blood products. Five patients received
granulocyte colony-stimulating factor (G-CSF) starting on day 1 after
marrow infusion until neutrophil recovery.
All patients had central venous catheters implanted on the day of
admission. Catheters were removed between days 100 and 150 after BM
transplantation (BMT). Informed consent was obtained from all patients
or their guardians.
Patients referred for ECP received baseline evaluations, including a
history and physical examination, complete blood count with
differential, and complete chemistry panel. When indicated, patients
were evaluated by an opthalmologist. Skin, liver, or mucous membrane
biopsies were performed as clinically indicated. Physical assessment
and laboratory studies were repeated every 2 weeks during the study.
Patients with extensive chronic GVHD received Pneumocystis
carinii and pneumococcal prophylaxis, as well as intravenous Ig replacement if infections occurred in the setting of Ig deficiency. Supportive care with artificial tear replacements, sun-blocking creams,
and oral caloric supplements was administered as required.
At study entry, all patients were in hematologic remission with donor
marrow engraftment.
One patient has been previously reported.13
Data were analyzed as of January 31, 1998. Survival rates were
estimated by the Kaplan-Meier method.
Evaluation criteria.
From 1993 on, all consecutive patients with chronic extensive GVHD were
treated with ECP; from 1996 on, patients with clinicopathologic diagnosis of acute GVHD resistant to steroid treatment were included. Because of the limited capacity at our institution, only a small number
of patients with acute GVHD could receive ECP.
The clinical diagnosis of GVHD was confirmed by histopathology of the
skin (see below) and, if indicated, liver biopsies and clinically
graded as 0 through IV for acute GVHD by the criteria reported19 and as none, limited, or extensive for chronic
GVHD.20 Progressive onset chronic GVHD developed as a
direct extension of acute GVHD, quiescent chronic GVHD occurred after
resolution of acute GVHD, and de novo chronic GVHD was not preceeded by
acute GVHD. Diagnosis was established upon review of clinical,
laboratory, and histologic data by previously published
criteria.19-22 Complete organ responses of chronic GVHD
were defined as resolution of skin, joint, oral mucosa, liver, or
ocular manifestations. Partial responses were defined as a greater than
50% response in organ involvement, but less than a complete response.
No change was defined as stable organ involvement, despite the tapering
of other immunosuppressive agents by at least 50% of the dosage. No
response referred to progressive worsening of chronic GVHD and the
inability to taper other medications.
ECP.
ECP was performed using the UVAR photopheresis system (Therakos, West
Chester, PA), as described.9,13 Briefly, 240 mL of buffy
coat and 300 mL of plasma were collected during each treatment by a
standard apheresis procedure and diluted with 200 mL of saline
solution. 8-MOP (0.2 mg; Gerot, Vienna, Austria) was added to the final
enriched lymphocyte solution containing 6 × 109
cells, as described.21 The solution was passed as a film,
1-mm thick, through a disposable plastic device, exposed to a UVA light source (2 J/cm2/cell) for 90 minutes, and then returned to
the patient. The mean treatment time for the photopheresis procedure
was 3.5 hours. Only peripheral vein catheters were used.
Treatment protocol.
ECP was initiated when the white blood cell count was greater than 1 × 109/L. Patients were treated on 2 consecutive days
at 2-week intervals for the first 3 months and thereafter every 4 weeks
until resolution of GVHD. All adverse effects observed during the
treatments were recorded. Informed consent was obtained by the
patients, and the use of ECP was approved by the local medical ethics
committee.
Skin biopsy.
Four-millimeter punch biopsies were performed at onset of cutaneous
GVHD, before ECP, and after 6 months on ECP. Skin biopsies were fixed
in formalin, embedded in paraffin, and stained with haematoxylin and
eosin. Sections were evaluated under the light microscope. The
histopathologic diagnosis of acute cutaneous GVHD grade II to IV was
based on the criteria and grading as suggested by Lerner et
al.22 Thus, basal cell vacuolization with or without further epidermal changes was graded as cutaneous GVHD I, whereas the
additional presence of single necrotic/apoptotic keratinocytes (mummified cells) and the presence of satellite lymphocytes was diagnosed as cutaneous GVHD II. Basal cleft formation together with the
above-described histological changes was used for establishing grade
III, and frank necrosis of the epidermis was regarded as a hallmark for
grade IV cutaneous GVHD. In addition to the epidermal changes,
mononuclear infiltrates were described as perivascular in acute
cutaneous GVHD.23 More pronounced epidermal changes in
addition to basal cell vacuolization, necrotic/apoptotic keratinocytes, satellite lymphocytes, hyperkeratosis, and acanthosis together with a
sparse bandlike infiltrate at the dermo-epidermal junction composed by
mononuclear cells were regarded as a typical lichen planus-like pattern
according to Shulman et al.24 Whenever atrophy of the epidermis with coarse collagen bundles and fibrosis/sclerosis of
the dermis with loss of skin appendages was observed, the histologic diagnosis of scleroderma-like cutaneous GVHD was made.
| |
RESULTS |
Response of patients with acute GVHD.
Six patients experienced acute GVHD II to III at a median of 16 days
(range, 12 to 21 days) after BMT and did not respond to CSA and
corticosteroids (2 mg to 10 mg/kg body weight) administered for a
median of 28 days, as shown in Table
2. Therefore, ECP was started after a median of 46 days
after BMT, allowing a rapid reduction of corticosteroids and
discontinuation after a median of 38 days without a further increase in
GVHD activity. In 4 of 6 patients, ECP was terminated after 9 to 13 cycles (Fig 1A) when complete resolution of
GVHD was observed (Table 2). Clinical results were confirmed by
histologic evaluation of skin biopsies with absence of basal cell
vacuolization and apoptotic cells as well as of satellite lymphocytes.
Perivascular mononuclear infiltrates within the upper dermis appeared
reduced or were absent. Immunosuppression with CSA was
continued, but the dosage was subsequently reduced (Fig 1A).
In one of these patients (patient no. 4), chronic limited GVHD of
skin and ocular mucosa evolved 28 months after BMT and 17 months after discontinuation of ECP. Another patient
(patient no. 1) developed chronic GVHD with chronic wasting
syndrome and keratoconjunctivitis 150 days after BMT. Two patients
who achieved partial resolution are still under ECP.
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| Fig 1.
Therapy of (A) acute and (B) chronic GVHD. On the x-axis,
the cycles of extracorporeal photochemotherapy (1 cycle = 1 therapy
on 2 consecutive days) are shown; on the y-axis, the number of patients
treated is shown.
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Response of patients with chronic GVHD.
Fifteen patients had extensive chronic GVHD after a median of 178 days
after BMT. Eight had a progressive presentation of chronic GVHD, 6 had
a quiescent onset, and 1 patient presented with de novo chronic GVHD,
as shown in Table 3. Histologically, 7 patients had sclerodermoid, 5 had combined lichenoid and
sclerodermatous, and 3 had lichen planus-like GVHD, as
described.23 Before ECP, immunosuppressive therapy
consisted of CSA (n = 11), steroids up to 2 mg/kg body weight
(n = 13), azathioprine (n = 1), thalidomide (n = 2), and PUVA (n = 2).
Because patients experienced increasing GVHD activity, ECP was started
after a median of 12 months (range, 3 to 44 months) after BMT (Table
3). At the initiation of ECP, 5 patients (33%) were receiving CSA
alone, 3 (20%) were receiving CSA and steroids, 4 (27%) were
receiving steroids alone, 1 (7%) were receiving steroids and
thalidomide, and 2 patients (13%) were receiving no systemic
immunosuppressive therapy. Patients received 7 to 47 cycles (median, 18 cycles) of ECP within 4 to 31 months, as shown in Table 3 and Fig 1B. During ECP, steroid therapy could be discontinuated after a median of 80 days. As of
January 31, 1998, 11 patients are off ECP, including 1 (patient no. 8) with abrupt discontinuation of ECP after relapse of
high- grade non-Hodgkin's lymphoma. Four patients are
currently under ECP because of partial resolution of GVHD
manifestations (n = 3) or recurrence of GVHD (n = 1) 3 months after
first discontinuation of ECP. Five patients remain under
immunosuppressive therapy.
Response rates for different organ involvement are shown in Table 3.
Twelve of 15 patients (80%) treated for chronic cutaneous GVHD
achieved a complete response with clinically normal appearing skin and
resolution of postinflammatory hyperpigmentation and fibrosis/sclerosis
(Fig 2). No difference in
response rates in sclerodermatous or lichenoid involvement was
observed. All patients with oral involvement showed a complete
response. Seven of 10 patients with liver involvement (70%)
experienced complete resolution, as seen in normalization of serum
bilirubin and alkaline phosphatase levels. Both patients with chronic
wasting syndrome markedly gained weight. Two of 3 patients
(67%) with thrombocytopenia had an increase in peripheral
blood platelet counts during ECP. All patients with contractures
experienced partial improvement in joint mobility. In 1 patient (17%),
ocular symptoms resolved completely; ocular symptoms resolved partially
in 4 patients (66%).
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| Fig 2.
Lichenoid GVHD involvement of the palms in patient no. 6 (Fig 1A) (A) before and (B) in complete remission after ECP.
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Infectious and toxic complications.
Nine of 15 patients (60%) experienced infections after the onset of
chronic GVHD before ECP. The most common infections were bacteremia in
patients with persistent central venous catheters (2 Staphylococcus, 1 Pseudomonas, 1 Hemophilus influenzae, and 1 Pneumococcus), pneumonia (2 Pneumococcus and 2 idiopathic), and CMV reactivation, as shown in
Table 4. During ECP, the predominant infectious complications were pansinusitis and pneumonia (1 Streptococcus, 1 Hemophilus influenzae, 1 Pneumococcus, and 1 idiopathic). No lethal infections occurred. After termination of ECP,
no further infections requiring antimicrobial or antiviral therapy were
seen.
Three of 6 patients with severe acute GVHD had a decrease in their ANC
after the first cycles of ECP without infectious complications. Two to
5 days later, their ANC increased again. One patient experienced heparin-induced thrombocytopenia and another patient experienced hemolytic uremic syndrome that resolved after CSA discontinuation and
plasmapheresis.
Survival.
All 6 patients treated for acute GVHD and 14 of 15 patients (93%) with
chronic GVHD are alive and well, with a median follow-up time after
termination of ECP of 5 months for acute GVHD and 15 months for chronic
GVHD. One patient died of a relapse of high-grade non-Hodgkin's
lymphoma 3 years after BMT. In the surviving patients, Karnofsky
performance scores improved from 50% before ECP to at least 90% after
ECP, respectively.
| |
DISCUSSION |
ECP has been shown to be effective in the treatment of cutaneous T-cell
lymphoma, autoimmune diseases such as pemphigus vulgaris, systemic
lupus erythematosus, progressive systemic sclerosis, and rejection
after organ transplantation.9-12 Because of the pathogenetic and clinical similarities of chronic GVHD to diseases responsive to ECP, this treatment modality has been already used in
selected patients with severe resistant chronic
GVHD.13-15,25 There, complete responses have been reported
in patients with skin (6/8), oral mucosal (3/6), liver (1/3), lung
(1/5), and gut (1/2) involvement.
Our report is the first to provide detailed information of the so-far
largest series of patients receiving ECP for chronic GVHD. Considering
the fact that only patients with histologically proven extensive
chronic GVHD were included in the study and that 87% had received
prior systemic immunosuppression without response, our results with ECP
appear to be very promising. Skin and oral mucosal affection due to
chronic GVHD completely resolved in 80% and 100% of patients,
respectively. Even liver involvement resolved completely in 70% of
patients. Partial responses were seen in patients with joint
involvement or keratoconjunctivitis.
Conventional treatment of GVHD, which usually includes prolonged and
high-dose corticosteroids, may be responsible for severe side effects,
including Cushing's syndrome, hypertension, renal failure, or
life-threatening infections. In our study at the initiation of ECP, all
patients with acute and 8 of 15 patients (53%) with chronic GVHD were
receiving steroids. Once ECP was started, gradual improvements allowed
a timely reduction and, finally, discontinuation of steroids without an
increase in GVHD activity. No deaths due to infections or metabolic
complications were observed in our patients. Respiratory infections and
particularly sinusitis are frequently seen in patients with chronic
GVHD resulting from a combination of the sicca syndrome in the sinuses
and a predisposition to bacterial infections.5 Reactivation
of latent CMV infection occurs in approximately 70% of
CMV-seropositive marrow graft recipients and 30% of CMV-seronegative
patients whose donors are seropositive.26 The use of ECP in
our group of patients did not increase the rate of infections compared
with results previously published.5,6 In fact, our findings
confirm reports on patients treated with ECP without increased
sensitivity to bacterial or viral infections.25
Because the risk of central venous catheter-related infectious
complications has to be considered in immunosuppressed patients, all
ECP treatments were performed by additional access through suitable
veins in the forearms. In view of the fact that no septicemia occurred
in our patients, we recommend this approach for future patients.
So far, only a few patients with acute GVHD treated with ECP without
achieving response have been reported.14,25 In our study,
complete resolution of both skin and liver involvement was seen in 4 of
6 patients with steroid-resistant acute GVHD, and 2 additional patients
are responding but currently still under ECP. Aside from a reversible
decrease in peripheral blood neutrophil counts during the first cycles
of ECP, when hematologic regeneration after BMT was still incomplete,
no major side effects were observed in these patients. The fact that in
our study ECP was administered over a substantially longer time period
as compared with previous reports14,25 may explain the
response rates achieved in our patients.
Our treatment schedule is based on the experience gained in patients
treated with ECP where ECP administered on 2 consecutive days appeared
to be more effective than single-day treatment
courses.9,12,25 Because our patients with extensive chronic
GVHD differed with regard to prior immunosuppressive therapies and
duration of GVHD on the one hand and the aim of this study was to
assess the efficacy and feasibility of ECP in these patients on the
other hand, treatment modalities applied in addition to ECP and therapy
duration varied. So far, after a median observation time of 12 months
after discontinuation of ECP, only 3 patients (14%) had recurrence of
GVHD. ECP was tolerated excellently, without any significant side
effects. The hemolytic uremic syndrome that had resolved after CSA
discontinuation was probably not related to ECP, because similar
observations have been reported on patients treated with CSA therapy
alone.27
The exact mechanisms by which ECP leads to the described responses in
GVHD as well as other T-cell-mediated diseases have not been
elucidated. The hypothesis that ECP may be involved in augmenting the
apoptotic process leading to deletion of graft reactive cells after
tolerance induction by donor bone marrow is supported by recent
observations and points to further directions of
investigations.28-31
In summary, our results demonstrate that ECP is a safe and efficacious
adjunct therapy for patients with both acute and chronic GVHD. However,
randomized studies are mandatory to evaluate the impact of
extracorporeal photochemotherapy on the course of GVHD and overall
survival.
| |
FOOTNOTES |
Submitted April 6, 1998;
accepted June 11, 1998.
Address reprint requests to Hildegard T. Greinix, MD, AKH
Wien, Klinik fuer Innere I, Knochenmarktransplantation, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" is accordance with 18 U.S.C. section 1734 solely to indicate this fact.
| |
ACKNOWLEDGMENT |
The authors thank the dedicated nurses of our stem cell transplant
program and the ECP unit, our fellows and house staff, the medical
technicians, and the physicians who referred patients to our unit.
| |
REFERENCES |
1.
Ferrara JLM,
Deeg HJ:
Graft-versus-host disease.
N Engl J Med
324:667,
1991[Medline]
[Order article via Infotrieve]
2.
Storb R,
Deeg HJ,
Whitehead J,
Appelbaum F,
Beatty P,
Bensinger W,
Buckner CD,
Clift R,
Doney K,
Farewell V,
Hansen J,
Hill R,
Lum L,
Martin P,
McGuffin R,
Sanders J,
Stewart P,
Sullivan K,
Witherspoon R,
Yee G,
Thomas ED:
Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.
N Engl J Med
314:729,
1986[Abstract]
3.
Beatty PG,
Clift RA,
Mickelson EM,
Nisperos BB,
Flournoy N,
Martin PJ,
Sanders JE,
Stewart P,
Buckner CD,
Storb R,
Thomas ED,
Hansen JA:
Marrow transplantation from related donors other than HLA-identical siblings.
N Engl J Med
313:765,
1985[Abstract]
4.
Doney KC,
Weiden PL,
Storb R,
Thomas ED:
Treatment of graft-versus-host disease in human allogeneic marrow graft recipients: A randomized trial comparing antithymocyte globulin and corticosteroids.
Am J Hematol
11:1,
1981[Medline]
[Order article via Infotrieve]
5.
Atkinson K:
Chronic graft versus host disease.
Bone Marrow Transplant
5:69,
1990[Medline]
[Order article via Infotrieve]
6.
Sullivan KM,
Witherspoon RP,
Storb R,
Deeg HJ,
Dahlberg S,
Sanders JE,
Appelbaum FR,
Doney KC,
Weiden P,
Anasetti C,
Loughran TP,
Hill R,
Shields A,
Yee G,
Shulman H,
Nims J,
Strom S,
Thomas ED:
Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-versus-host disease.
Blood
72:555,
1988[Abstract/Free Full Text]
7.
Sullivan KM,
Witherspoon RP,
Storb R,
Weiden P,
Flournoy N,
Dahlberg S,
Deeg HJ,
Sanders JE,
Doney KC,
Appelbaum FR,
McGuffin R,
McDonald GB,
Meyers J,
Schubert MM,
Gauvreau J,
Shulman HM,
Sale GE,
Anasetti C,
Loughran TP,
Strom S,
Nims J,
Thomas ED:
Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-versus-host disease: Prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation.
Blood
72:546,
1988[Abstract/Free Full Text]
8.
Volc-Platzer B,
Hönigsmann H,
Hinterberger W,
Wolff K:
Photochemotherapy improves chronic cutaneous graft-versus-host disease.
J Am Acad Dermatol
23:220,
1990[Medline]
[Order article via Infotrieve]
9.
Knobler RM,
Graninger W,
Lindmaier A,
Trautinger F,
Smolen J:
Extracorporeal photochemotherapy for the treatment of systemic lupus erythematosus.
Arthritis Rheum
35:319,
1992[Medline]
[Order article via Infotrieve]
10.
Costanzo-Nordin MR,
Hubbell EA,
O'Sullivan EJ,
Robinson JA:
Successful treatment of heart transplant rejection with photopheresis.
Transplantation
53:808,
1992[Medline]
[Order article via Infotrieve]
11.
Edelson RL,
Heald PW,
Perez MI,
Berger C:
Extracorporeal photochemotherapy.
Biol Ther Cancer Updates
4:1,
1994
12.
Sunder-Plassmann G,
Druml W,
Steininger R,
Hönigsmann H,
Knobler R:
Renal allograft rejection controlled by photopheresis.
Lancet
346:506,
1995
13.
Gerber M,
Gmeinhart B,
Volc-Platzer B,
Kalhs P,
Greinix H,
Knobler R:
Complete remission of lichen-planus-like graft-versus-host disease (GVHD) with extracorporeal photochemotherapy (ECP).
Bone Marrow Transplant
19:517,
1997[Medline]
[Order article via Infotrieve]
14.
Besnier DP,
Chabannes D,
Mahe B,
Mussini JMG,
Baranger TAR,
Muller JY,
Milpied N,
Esnault VLM:
Treatment of graft-versus-host disease by extracorporeal photochemotherapy.
Transplantation
64:49,
1997[Medline]
[Order article via Infotrieve]
15.
Dall'Amico R,
Rossetti F,
Zulian F,
Montini G,
Murer L,
Andreetta B,
Messina C,
Baraldi E,
Montesco MC,
Dini G,
Locatelli F,
Argiolu F,
Zacchello G:
Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease.
Br J Haematol
97:848,
1997[Medline]
[Order article via Infotrieve]
16.
Thomas ED,
Storb R,
Clift RA,
Fefer A,
Johnson FL,
Neiman PE,
Lerner KG,
Glucksberg H,
Buckner CD:
Bone marrow transplantation.
N Engl J Med
292:832,
1975[Medline]
[Order article via Infotrieve]
17.
Przepiorka D,
Shapiro S,
Schwinghammer TL,
Bloom EJ,
Rosenfeld CS,
Shadduck RK,
Venkataramanan R:
Cyclosporine and methylprednisolone after allogeneic marrow transplantation: Association between low cyclosporine concentration and risk of acute graft-versus-host disease.
Bone Marrow Transplant
7:461,
1991[Medline]
[Order article via Infotrieve]
18.
Winston DJ,
Gale RP:
Prevention and treatment of cytomegalovirus infection and disease after bone marrow transplantation in the 1990s.
Bone Marrow Transplant
8:7,
1991[Medline]
[Order article via Infotrieve]
19.
Rowlings PA,
Przepiorka D,
Klein JP,
Gale RP,
Passweg JR,
Henslee-Downey PJ,
Cahn JY,
Calderwood S,
Gratwohl A,
Socie G,
Abecasis MM,
Sobocinski KA,
Zhang MJ,
Horowitz MM:
IBMTR severity index for grading acute graft-versus-host disease: Retrospective comparison with Glucksberg grade.
Br J Haematol
97:855,
1997[Medline]
[Order article via Infotrieve]
20.
Sullivan KM,
Shulman HM,
Storb R,
Weiden PL,
Witherspoon RP,
McDonald GB,
Schubert MM,
Atkinson K,
Thomas ED:
Chronic graft-versus-host disease in 52 patients: Adverse natural course and successful treatment with combination immunosuppression.
Blood
57:267,
1981[Abstract/Free Full Text]
21.
Knobler RM,
Trautinger F,
Graninger W,
Macheiner W,
Gruenwald C,
Neumann R,
Ramer W:
Parenteral administration of 8-methoxypsoralen in photopheresis.
J Am Acad Dermatol
28:580,
1993[Medline]
[Order article via Infotrieve]
22.
Lerner KG,
Kao GF,
Storb R:
Histopathology of graft-versus-host reaction (GVHR) in human recipients from HLA-matched sibling donors.
Transplant Proc
6:367,
1974[Medline]
[Order article via Infotrieve]
23.
Horn TD,
Zahurak ML,
Atkins D,
Solomon AR,
Vogelsang GB:
Lichen planus-like histopathologic characteristics in the cutaneous graft-vs-host reaction.
Arch Dermatol
133:961,
1997[Abstract]
24.
Shulman HM,
Sullivan KM,
Weiden PL,
McDonald GB,
Striker GE,
Sale GE,
Hackman R,
Tsoi MS,
Storb R,
Thomas ED:
Chronic graft-versus-host syndrome in man: A clinicopathological study of 20 long-term Seattle patients.
Am J Med
69:204,
1980[Medline]
[Order article via Infotrieve]
25.
Sniecinski I:
Extracorporeal photochemotherapy: A scientific overview.
Transfus Sci
15:429,
1994[Medline]
[Order article via Infotrieve]
26.
Goodrich JM,
Mori M,
Gleaves CA,
Du Mond C,
Cays M,
Ebeling DF,
Buhles WC,
DeArmond B,
Meyers JD:
Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation.
N Engl J Med
325:1601,
1991[Abstract]
27.
Zoja C,
Furci L,
Ghilardi F,
Zilio P,
Benigni A,
Remuzzi G:
Cyclosporin-induced endothelial cell injury.
Lab Invest
55:455,
1986[Medline]
[Order article via Infotrieve]
28.
Aringer M,
Graninger WB,
Smolen JS,
Kiener HP,
Steiner LW,
Trautinger F,
Knobler R:
Photopheresis treatment enhances CD95 (fas) expression in circulating lymphocytes of patients with systemic sclerosis and induces apoptosis.
Br J Rheumatol
36:1267,
1997
29.
Yoo EK,
Rook AH,
Elenitsas R,
Gasparro FP,
Vowels BR:
Apoptosis induction by ultraviolet light A and photochemotherapy in cutaneous T-cell lymphoma: Relevance to mechanism of therapeutic action.
J Invest Dermatol
108:235,
1996
30.
Enomoto DN,
Schellekens PT,
Yong SL,
Ten Berge IJ,
Mekkes JR,
Bos JD:
Extracorporeal photochemotherapy (photopheresis) induces apoptosis in lymphocytes: A possible mechanism of action of PUVA therapy.
Photochem Photobiol
65:177,
1997[Medline]
[Order article via Infotrieve]
31.
George JF,
Sweeney SD,
Kirlin JK,
Simpson EM,
Goldstein DR,
Thomas JM:
An essential role for fas ligand in transplantation tolerance induced by donor bone marrow.
Nat Med
4:333,
1998[Medline]
[Order article via Infotrieve]
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Abstract
Introduction
Abstract