Clinical trial NCT02631993: Photochemotherapy and Graft-versus-leukemia in Acute-leukemia
Official title: Photochemotherapy of Acute Graft-versus-host Disease (aGVHD) of the Skin - is Graft-versus-leukemia Preserved in Patients Transplanted for Acute Leukemia?
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ALL
AML
Acute GVHD
Tumor Immunity
Keywords: Psoralen
UVA
Time-to-treatment
GVL
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2015-12-16
Enrollment: 47
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with AML or ALL having received photochemotherapy for aGVHD evoked by HSCT given at Center for Allogeneic Stem Cell transplantation (CAST) between 1985 - end of 2004.

Brief summary: Cure of leukemia after hematopoietic stem cell transplantation (HSCT) is sustained by the anti-leukemic effect of the grafted cells (graft-versus-leukemia (GVL)). However, it is not known whether the tumor-immunity is affected by photochemotherapy (psoralene photosensitization and ultraviolet light radiation) administered to attenuate graft-versus host disease (GVHD).

The present study aim to investigate what happens to the GVL after photochemotherapy of aGVHD in a predominantly retrospective setting with 10-years follow-up after HSCT

Detailed description: This is a 10-year follow-up of patients with Acute-myeloid-leukemia (AML) or acute-lymphatic-leukemia (ALL). AML is diagnosed by the French-American-British criteria (FAB-criteria) and ALL is separated into chief forms by immunohistological methods. All patients underwent myeloablative Hematopoietic Stem Cell Transplantation (HSCT) between 1985 and 2005 at the center for allogeneic stem cell transplantation (CAST) at Karolinska University Hospital. All patient receive GVHD-prophylaxis.

The risk for relapse after HSCT is graded into low-risk if the disease is in first complete remission before HSCT, all other disease states are classified as high-risk.

Eligible patients received photochemotherapy (Ultraviolet radiation type A on skin photosensitized by oral 8-methoxypsoralen) for acute graft-versus-host disease (GVHD within 100-days after HSCT). Photochemotherapy may be given as primary or later aGVHD therapy. Patients with aGVHD after booster doses of stem-cells or donor-lymphocyte-infusions are not included.

Additional treatment are registered where present. Methotrexate is not considered as an additional GVHD treatment as intravenous methotrexate a part of the governing GVHD prophylaxis and as the effects of methotrexate as a secondary aGVHD treatment is weak.

At the start, the end, at maximum and up until two weeks after end of PUVA-therapy the GVHD is diagnosed in accordance with Glucksberg and indexed by CIBMTR.

Relapse is diagnosed when leukemic cells is present extra medullary or with a bone marrow biopsy with ≥ 30% blasts. Early relapse is diagnosed when the medulla contain 5 - 30% blasts

The primary outcome is GVL i.e. abscence of relapse in malignant disease or minimal residual disease (MRD) i.e. threatening relapse in malignant disease demanding donor lymphocyte infusion (DLI).

Primary predictor: Time-to-treatment by photochemotherapy at day 0 - 7 vs. start at day 8 ≤ of aGVHD.

Continuous secondary predictor: Time-to-treatment by photochemotherapy as a continuous variable (days after start of aGVHD).

Binary secondary predictors: Risk (Low/High), Sibling donor-recipient (Yes/No), Mismatched related (Yes/No), Unrelated donor (Yes/No), (Male recipients of female grafts (Yes/No), T-cell depletion or Anti-Thymocyte Globulin (Yes/No).

Categorical secondary predictors: AGVHD organ disease stage and disease grade; Skin (+, ++, +++, ++++), Liver (+, ++, +++, ++++), Gastro-intestinal (+, ++, +++, ++++), Center for International Blood and Marrow Transplant Research CIBMTR index (A, B, C, D) respectively.

Statistical analysis:

Cox proportional Hazards ratio is used to conduct a univariate data analysis of all adequate variables in patient characteristics and disease towards the primary outcome. In the analysis, death, DLI or retransplantation due to graft-failure was treated as a competing event. The primary predictor (binary) and all binary or categorical covariates identified from the patient and disease characteristics are to be included in a multivariate forward regression analysis, controlled for with backward regression based on the log-likelihood method. P=0.05 is considered as significant and p=0.10 as a trend. StatSoft, Inc. (2013). STATISTICA (data analysis software system), version 12. www.statsoft.com. are used for statistical computation.

Eligibility criteria: Inclusion Criteria:

* Eligible patients received photochemotherapy (Ultraviolet radiation type A on skin photosensitized by oral 8-methoxypsoralen) for acute graft-versus-host disease (GVHD within 100-days after HSCT). Photochemotherapy may be given as primary or later aGVHD therapy.

Exclusion Criteria:

* Patients with aGVHD after booster doses of stem-cells or donor-lymphocyte-infusions are not included.

Primary outcomes:
measure: Graft-versus-leukemia (GVL)
timeFrame: 10-years after HSCT (2005 - 2015)
Secondary outcomes:
measure: Death
timeFrame: 10-years after HSCT (2005 - 2015)
measure: Retransplantation
timeFrame: 10-years after HSCT (2005 - 2015)
measure: Donor Lymphocyte Infusion (DLI)
timeFrame: 10-years after HSCT (2005 - 2015)
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Department of Dermatology, Karolinska University Hospital Huddinge
Study officials:
affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institute
name: Nicolas Feldreich, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institute
name: Olle Ringden, Professor
role: STUDY_DIRECTOR
affiliation: Department of Oncology and Pathology,
name: Brigitta Omazic, PhD
role: STUDY_CHAIR
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