ASCP Check Sample Transfusion Medicine 048

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ASCP Check Sample Transfusion Medicine 04-8

• Daniel K. Noland, MD
• October 25, 2005

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Case History

• 13 y.o. male with ALL who initially responded to
  chemotherapy
• First relapse three years later tx- bone marrow
  transplant from an unrelated donor
• Second relapse two years later tx-infusion with T
  cells collected from original marrow donor to
  induce graft-versus-leukemia effect.

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Case History II

• Presented two weeks after T-cell infusion with
  fever, rash and diarrhea
• Started on Prednisone, but fevers persisted and
  diarrhea worsened
• He was admitted to the hospital and after drawing
  blood cxs multiple antibiotics were begun
• Inc LFTs, dec Na, CO2, Hgb, WBCs, Plts

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Case History III

• GI and Liver Graft Versus Host Disease confirmed
  on biopsy
• Worsened despite multi-drug immunosuppressive
  therapy
• Developed jaundice, massive painful ascites
  requiring morphine

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Final Case History

• Additional complicationsMarrow aplasia requiring
  transfusion, and renal failure due to
  polypharmacy
• Oncology team consulted apheresis service for
  possible photopheresis, but the patient quickly
  expired due to complications of his disease.

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Graft Versus Host Disease

• Despite T-cell depletion and immunoprophylaxis-sti
  ll a common complication of any non-autologous
  bmt
• Donor T-cells attack recipient tissue with
  resulting cytokine release and tissue damage
• Both CD4 and CD8 T cells are implicated
• There is both an acute and a chronic form

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Acute GVHD

• Usually occurs at time of engraftment but defined
  as w/in 100 days of allogenic trans.
• 30-40 of HLA identical, up to 80 of unrelated
  transplants
• Affects Skin, GI tract and Liver
• Graded by site (liver worst), clinical severity
  of symptoms, and bilirubin level

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Chronic GVHD

• More than 100 days post-transplant by itself or
  s/p Acute GVH
• Incidence 30 HLA-identical sibs, 50 of
  unidentical, and 60 matched unrelated txs
• In addition to acute GVHD symptoms, chronic dz
  also includes sicca, pulmonary dz, wasting
  syndrome, esophageal and vaginal strictures, etc.

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Alphabet Soup

• While GVHD is a significant complication, the
  Graft Versus Leukemia (GVL) response (in which
  Graft cytotoxic T cells attack residual leukemia)
  is thought beneficial
• Indeed, Donor Lymphocyte Infusion (DLI) is used
  to treat relapse after bmt
• One should say peripheral blood progenitor
  cell(PBPC) tx as they are supplanting bmt

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Current GVHD therapy

• Combined tx corticosteroid plus cyclosporin A,
  tacrolimus, methotrexate, mycophenolate mofetil,
  and/or antilymphocyte globulin
• Lack of response to steroid is worrisome so most
  consider non-FDA approved therapies such as..

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Photopheresis

• Story starts in ancient Egypt extract from the
  Ammi Majus plant made people sun-burn easily but
  also helped vitiligo
• Active ingredient psoralen FDA approved
  derivative8-methoxypsoralen or 8-MOP
• There are two steps treatment with psoralen and
  photoactivation with UVA radiation
• Psoralen can be given systemically or.

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Photopheresis2

• Psoralen can be added to the Monos after they are
  removed by leukopheresis.
• There are also two options for radiation
  external beam and extracorporeal after
  leukopheresis.
• This leads to three treatment options 1)give
  systemic (PO) psoralen and then do leukopheresis
  and treat with ECP UV-A

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Photopheresis3

• Two (most common) leukopheresis, psoralen and
  UV-A photoactivation ECP, reinfusion of treated
  cells
• Three (used for Mycosis Fungoides) PO psoralen,
  followed 2 hours later by external beam UV-A
  photoactivation
• Theoretically, one could leukopheresis, psoralen
  tx the Monos, and reinfuse prior to external beam
  UV-A but why would you?

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Photopheresis 4

• Mechanism of action by which treating monos
  treats T cell disease is unknown
• one theory is that monos become dendritic cells
  which present antigen and induce apoptosis
• FDA approved to treat Cutaneous T-Cell Lymphoma
  even disseminated (Sezary syndrome)

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Photopheresis5

• Few side effects are mainly due to pheresis
  (anticoagulant reactions, hypovolemia, etc.)
• Anemia not usually a problem as trying to keep
  crit of product under 4 so RBCs dont block UV
  from getting to Monos
• Low grade fever 4 to 12 hours s/p reinfusion
  (probably Monocyte cytokines)
• Protect skin and eyes from sunlight x24h

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Photopheresis in Acute GVHD

• Check sample authors compiled 11 studies of 76
  patients treated with photopheresis
• Age, time since transplant, and tx cycle
  number/freq/duration all varied sig.
• All pts had failed traditional drug tx
• Which may be why 33 (47) died (mostly
  opportunistic infxns or organ failure)

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Organs Involved by acute GVHD
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Photopheresis Chronic GVHD

• 204 patients in 20 studies where parameters
  (age, transplant to tx time, ECP treatment
  duration/dose/ freq, etc.) varied widely
• All had failed immunosuppressive therapy
• 79 overall survival, with better prognosis in
  patients were ECP was started earlier
• number of medications could be reduced in 60 of
  patients

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ExtraCorporeal Photophoresis in solid organ
rejection

• Cardiac one study showed reversal of rejection
  in 8/9 ECP patients and 7/7 steroid tx pts.
  Another showed people randomized to ECP plus
  standard tx had fewer episodes of rejection
• Lung 8 pts who had failed drug tx, 5/8
  stabilized PFTs, 2/8 had histologic reversal
• Kidney 4/4 responded, inc Cr clearance and dec
  drugs in 3/4

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ECP in Autoimmune Disorders

• 79 patients w/new onset Systemic Sclerosis
  randomized to penicillamine or ECP. Skin
  severity score improved in 68 ECP vs 32
  D-penicillamine. Symptoms worse in 10 ECP tx,
  32 D-penicillamine
• RA 4/7 less symptoms and 2-3 mo delay in
  deteriatiration
• SLE 7/8 had improved clinical activity score
  no change in lab parameters