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Extracorporeal photochemotherapy: A new therapeutic approach for allograft rejection

Dall'Amico Roberto , Murer Luisa
  • Transfusion & Apheresis Science. 2002 June,; 26(3):197-204.
Photopheresis (ECP) is a new immunomodulatory therapy in which recipient lymphocytes are treated extracorporeally with 8-methoxypsoralen (8-MOP) and ultraviolet light. The treatment seems to induce an inhibition of both umoral and cellular rejections after transplantation. More than 160 transplanted patients have been treated with ECP (107 heart, 30 kidney, 24 lung and 1 liver) in different studies. Indication for ECP included acute rejection, recurrent/refractory rejection, prophilaxis of rejection, need of reducing standard immunosuppression. Patient survival is satisfactory. Only one study where ECP was used as the last therapeutic resource in very compromised patients shows a high rate of mortality. On the contrary, when ECP was used earlier after the failure of a first immunosuppressive line the outcome was better with a very low mortality. An hystological resolution of acute rejection is reported in 89% of cardiac transplant patients. The rate of response is similar even in the other transplanted patients treated with ECP. A better control of alloreactivity has been also reported in both cardiac and renal transplant patients with recurrent rejection. In renal allograft the treatment induces a reduction of both lymphocytes and monocytes infiltrate and downregulates the expression of HLA-DR and integrins ICAM-1 and VCAM-1 on tubular cells. Markers of fibrogenesis such as TGFbeta1 and ASMA are only moderately reduced with a more focal pattern of distribution in the post-ECP specimens. The optimal schedule and the length of treatment are still unclear and probably a patient-tailored treatment is needed at least in responder patients. ECP is effective for patients resistant to conventional treatments, particularly when it is started early. This beneficial effect is obtained without the complications typically encountered with immunosuppressive regimens used to control rejection.

https://pubmed.ncbi.nlm.nih.gov/12126206/

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Successful treatment of recurrent rejection in renal transplant patients with photopheresis.

Dall'Amico R , Murer L , Montini G , Andreetta B , Zanon GF , Zacchello G , Zacchello F
  • Journal of the American Society of Nephrology. 1998 Jan; 9(1):121-7.
Photopheresis (ECP) is a new form of photochemotherapy that induces a selective inhibition of the host response to foreign histocompatibility antigens and reverses allograft rejection after organ transplantation. This report describes four adolescent patients with recurrent rejection episodes after renal transplantation, all uncontrolled using standard protocols of immunosuppression (intravenous steroids and OKT3), yet successfully treated with a 6-mo course of ECP. The ECP treatment was performed at weekly intervals during the first month, at 2-wk intervals during the second and third months, and then monthly for another 3 mo. Creatinine clearance improved throughout the treatment in three patients and remained unchanged in one. All patients had a pre-ECP biopsy with a grade 2 or 3 rejection (Banff) with a diffuse infiltrate CD8, CD14, LFA-1 (166 cells positive/0.048 mm2), and VLA-4 (51 cells positive/0.048 mm2) positive, as well as a tubular expression of HLA-DR (6.2 sections of tubule positive/0.048 mm2), ICAM-1, and VCAM-1 (3.1 and 2.9 sections of tubule positive/0.048 mm2). A strong reduction of cell infiltrate and expression of LFA-1 (6.6 cells positive/0.048 mm2). VLA-4 (0.7 cells positive/0.048 mm2), HLA-DR (0.2 section of tubules positive/0.048 mm2), ICAM-1 (0.3 section of tubules positive/0.048 mm2), and a disappearance of VCAM-1 staining were observed in the biopsies performed after 3 mo of ECP. All patients remained rejection-free during ECP, without infections or other complications commonly observed with increasing doses of standard immunosuppression. The clinical improvement allowed a progressive reduction of oral steroids in three of the four patients treated.

https://pubmed.ncbi.nlm.nih.gov/9440096

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Benefits of photopheresis in the treatment of heart transplant patients with multiple/refractory rejection.

Dall'Amico R , Montini G , Murer L , Andreetta B , Tursi V , Feltrin G , Guzzi G , Angelini A , Zacchello G , Livi U
  • Transplantation Proceedings. 1997 Feb; 29(1-2):609-11.
No abstract available

https://pubmed.ncbi.nlm.nih.gov/9123152

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Reversal of acute renal allograft rejection by extracorporeal photopheresis: a case presentation and review of the literature.

Wolfe JT , Tomaszewski JE , Grossman RA , Gottlieb SL , Naji A , Brayman KL , Kobrin SM , Rook AH
  • Journal of Clinical Apheresis. 1996; 11(1):36-41.
There is a clear need for well-tolerated immunomodulatory agents that can aid in the prevention of acute solid organ rejection. Extracorporeal photopherosis is an apheresis-based therapy that is currently available at many medical centers worldwide. Preliminary studies utilizing photopheresis with standard immunosuppressives have shown this therapy to successfully reverse acute cellular rejection of cardiac allografts with minimal toxicity. No formal evaluation of the role of extracorporeal photopheresis had been performed in renal transplantation. In this report, photopheresis was successfully utilized to treat acute cellular rejection in a patient with a renal allograft. This lends further support to the existing literature suggesting that photopheresis may be useful for the reversal of acute solid organ rejection. Although our experience with this patient is anecdotal, photopheresis merits further study as treatment for severe renal allograft rejection.

https://pubmed.ncbi.nlm.nih.gov/8722721

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T-cell Lymphoma: relevance to mechanism of therapeutic action.

Yoo EK , Rook AH , Elenitsas R , Gasparro FP , Vowels BR
  • Journal of Investigative Dermatology. 1996 Aug; 107(2):235-42.
The anti-tumor action of many chemotherapeutic agents has recently been attributed to the induction of apoptosis in the malignant cell population. In this study, we investigated the ability of extracorporeal photopheresis (ExP) and in vitro PUVA (8-methoxy-psoralen + ultraviolet A) therapy to induce apoptosis in peripheral blood mononuclear cells from Sezary syndrome patients and normal controls. Flow cytometric analysis of ExP- or PUVA-treated peripheral blood lymphocytes demonstrated two distinct cell populations within 24 h of treatment. One population was similar to untreated controls with the other exhibiting characteristics of apoptotic cell death, i.e., a loss of cell volume and an accompanying increase in cell density. This latter population was comprised of cells with DNA strand breaks as determined by the Tdt-mediated deoxyuridine triphosphate-biotin nick end labeling assay. Apoptosis was also confirmed morphologically by fluorescent and electron microscopy as well as by demonstration of characteristic DNA strand breaks (laddering) using gel electrophoresis. Apoptosis was not observed with 8-methoxypsoralen (< or = 300 ng per ml) alone; however, ultraviolet A alone at doses > or = 2 J per cm2 induced apoptosis in lymphocytes. Peripheral blood T-cell subpopulations of Sezary syndrome patients, including the malignant clone, were equally susceptible to apoptosis subsequent to either photopheresis or PUVA treatment. In contrast, monocytes (CD14+/CD45+) appear to be resistant to apoptosis induction by ExP or PUVA treatment. Moreover, ExP-treated and untreated monocytes phagocytized apoptotic, but not untreated, peripheral blood mononuclear cells. ExP and PUVA have been shown to be efficacious and well-tolerated therapies in the treatment of dermatologic diseases and transplant rejection. These data suggest that induction of apoptosis may be an important event for therapeutic efficacy.

https://pubmed.ncbi.nlm.nih.gov/8757769

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Renal allograft rejection controlled by photopheresis.

Sunder-Plassman G , Druml W , Steininger R , Honigsmann H , Knobler R
  • Lancet. 1995 Aug 19;346(8973):506. doi: 10.1016/s0140-6736(95)91355-6.
No abstract available

https://pubmed.ncbi.nlm.nih.gov/7637500

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Photopheresis for renal allograft rejection.

Horina JH , Mullegger RR , Horn S , Holzer H , Halwachs G , Kerl H , Wolf P
  • Lancet. 1995 Jul 1;346(8966):61. doi: 10.1016/s0140-6736(95)92696-8.
No abstract available

https://pubmed.ncbi.nlm.nih.gov/7603177

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Photopheresis for chronic rejection of lung allografts.

Slovis BS , Loyd JE , King LE Jr
  • New England Journal of Medicine. 1995 Apr 06; 332(14):962.
No abstract available

https://pubmed.ncbi.nlm.nih.gov/7877665

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Extracorporeal photochemotherapy as adjuvant treatment of heart transplant recipients with recurrent rejection.

Dall'Amico R , Livi U , Montini G , Andreetta B , Murer L , Zacchello G , Zacchello F
  • Transplantation. 1995 Jul 15; 60(1):45-9.
Recurrent rejection is an uncommon, severe complication after heart transplantation that is associated with a poor long-term prognosis. Photopheresis (ECP), a new form of extracorporeal photo-chemotherapy used for the treatment of cutaneous T cell lymphoma and several autoimmune diseases, has also been used for prevention and treatment of acute rejection in heart transplant recipients. It seems to induce specific suppression of both cellular and humoral rejection. In this study, we evaluated whether ECP added to standard therapies allowed better control of rejection and reduction of conventional immunosuppressive drugs in patients with repeated rejection episodes. Eight heart transplant recipients (6 men and 2 women, mean age 48 yr), with recurrent rejection were treated with ECP for 6 months. Endomyocardial biopsies (EMB) were performed monthly. As a result of treatment, 7 patients on ECP experienced a reduction of the number and severity of rejection episodes. The fraction of EMB negative for rejection increased from 13 to 41%, whereas the fraction of specimens with multifocal and/or diffuse moderate lymphocytes infiltration (grades 3A and 3B) decreased from 41 to 21%. ECP allowed reductions of daily immunosuppressive therapy: prednisone by 44% (16.9 vs. 9.4 mg), cyclosporine by 21% (366 vs. 291 mg), and azathioprine by 29% (137 vs. 97 mg). No major side effects were observed. We conclude that, although the number of patients is small, the use of ECP was safe and associated with improved control of recurrent rejection. This allowed tapering of immunosuppressive drugs, which was particularly useful in two patients with insulin-dependent diabetes and one with sternal wound osteomyelitis.

https://pubmed.ncbi.nlm.nih.gov/7624941

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 

Treatment of severe cardiac allograft rejection with extracorporeal photochemotherapy.

Wieland M , Thiede VL , Strauss RG , Piette WW , Kapelanski DP , Landas SK , Hunsicker LG , Vance SJ , Randels MJ
  • Journal of Clinical Apheresis. 1994; 9(3):171-5.
Two patients were treated with photopheresis for marked cardiac allograft rejection with hemodynamic compromise that had become unresponsive to standard therapy. Multiple episodes of rejection had occurred, and initial response to standard therapy was favorable. However, progressive deterioration was documented by serial endomyocardial biopsies, fever, congestive heart failure, and abnormal cardiac catheterization findings. In the absence of retransplantation, death seemed imminent. Photopheresis was begun. Both patients received oral 8-methoxypsoralen and > or = 5 x 10(9) mononuclear cells were collected, treated with ultraviolet light A for 1.5 hours, and were reinfused. One procedure was performed weekly x4 and then monthly x5. Responses were striking with rapid loss of fever, improvement in exercise tolerance, normalization of cardiac hemodynamics, and improvement in endomyocardial biopsies. Although our experience with these two patients is anecdotal, photopheresis merits further study as treatment for severe cardiac allograft rejection.

https://pubmed.ncbi.nlm.nih.gov/7706199

BACKGROUND:
There is no standard definition for “HLA incompatible” transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes.
 
METHODS:
We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility.
 
RESULTS:
Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains.
 
CONCLUSIONS:
Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
 
 
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