Page 1900 - Hematology_ Basic Principles and Practice ( PDFDrive )

1682 Part X Transplantation

intensifying initial immunosuppression have not been consistently Betts BC, Young JA, Ustun C, et al: Human herpesvirus 6 infection after
effective in preventing subsequent chronic GVHD. As with acute hematopoietic cell transplantation: is routine surveillance necessary? Biol
GVHD, the specific immunosuppressive therapy for chronic GVHD Blood Marrow Transplant 17(10):1562–1568, 2011.
is most often corticosteroids, usually in combination with cyclospo- Boeckh M, Ljungman P: How we treat cytomegalovirus in hematopoietic cell
rine. The ongoing and long lasting nature of the syndrome demands transplant recipients. Blood 113(23):5711–5719, 2009.
that reduced doses and, if possible, alternate day steroid therapy be Bolanos-Meade J, Logan BR, Alousi AM, et al: Phase 3 clinical trial of
used to minimize chronic complications of prolonged corticosteroid steroids/mycophenolate mofetil vs steroids/placebo as therapy for
therapy. Typical corticosteroid regimens start with daily prednisone acute GVHD: BMT CTN 0802. Blood 124(22):3221–3227, 2014;
1 mg/kg per day and responding patients are tapered down to quiz 3335.
0.5–1 mg/kg every other day and continued on this dose for 6–9 Ciurea SO, Thall PF, Wang X, et al: Donor-specific anti-HLA Abs and graft
months beyond any active GVHD symptoms, followed by a slow failure in matched unrelated donor hematopoietic stem cell transplanta-
withdrawal of immunosuppression. Longer therapy may be required tion. Blood 118(22):5957–5964, 2011.
for some patients, and early withdrawal of therapy has been frequently Ferrara JL, Levine JE, Reddy P, et al: Graft-versus-host disease. Lancet
accompanied by flares of chronic GVHD. Salvage therapies including 373(9674):1550–1561, 2009.
high-dose corticosteroids, sirolimus, tacrolimus, MMF, thalidomide, Filipovich AH, Weisdorf D, Pavletic S, et al: National Institutes of Health
azathioprine, and hydroxychloroquine have been tried with limited consensus development project on criteria for clinical trials in chronic
response rates. Newer approaches currently being investigated as graft-versus-host disease: I. Diagnosis and staging working group report.
potential therapies for chronic GVHD include modulation of T-cell Biol Blood Marrow Transplant 11(12):945–956, 2005.
function, B-cell depletion, induction of immune tolerance and Foley B, Cooley S, Verneris MR, et al: Cytomegalovirus reactivation after allo-
cytokine blockade. Small uncontrolled studies have reported the use geneic transplantation promotes a lasting increase in educated NKG2C+
of pentostatin, alemtuzumab and ATG to inhibit T-cell function and natural killer cells with potent function. Blood 119(11):2665–2674,
rituximab to eliminate B-cells with response rates of 30% to 50%. 2012.
T-cell immunomodulation using extracorporeal photopheresis has Freifeld AG, Bow EJ, Sepkowitz KA, et al: Clinical practice guideline for the
been shown to have some activity, especially in sclerotic cutaneous use of antimicrobial agents in neutropenic patients with cancer: 2010
chronic GVHD. Preliminary studies using daclizumab, etanercept, Update by the Infectious Diseases Society of America. Clin Infect Dis
and infliximab for blockade of the cytokine-mediated inflammatory 52(4):427–431, 2011.
response have also shown short-term responses. The treatment of Gooley TA, Chien JW, Pergam SA, et al: Reduced mortality after allogeneic
chronic GVHD demands particular attention to prophylaxis and hematopoietic-cell transplantation. N Engl J Med 363(22):2091–2101,
aggressive therapy of secondary opportunistic infections. Most suc- 2010.
cessful strategies for treating chronic GVHD incorporate long-term Holtan SG, DeFor T, Lazaryan A, et al: Composite end point of graft-versus-
reduced-dose immunosuppressive therapy, aggressive antimicrobial host disease-free, relapse-free survival after allogeneic hematopoietic cell
prophylaxis and supportive care. Strategies favoring development of transplantation. Blood 125(8):1333–1338, 2015.
donor-derived regulatory T cells which may facilitate the development MacMillan ML, Weisdorf DJ, Brunstein CG, et al: Acute graft-versus-host
of immunologic tolerance including avoidance of calcineurin inhibi- disease after unrelated donor umbilical cord blood transplantation:
tors (cyclosporine or tacrolimus) or photopheresis are being studied. analysis of risk factors. Blood 113(11):2410–2415, 2009.
Majhail NS, Parks K, DeFor TE, et al: Diffuse alveolar hemorrhage and
infection-associated alveolar hemorrhage following hematopoietic stem
FUTURE DIRECTIONS cell transplantation: related and high-risk clinical syndromes. Biol Blood
Marrow Transplant 12(10):1038–1046, 2006.
Complications of HCT are one of the major barriers to the wider Majhail NS, Rizzo JD, Lee SJ, et al: Recommended screening and preventive
application of transplantation for a variety of diseases. Currently, only practices for long-term survivors after hematopoietic cell transplantation.
one in four adult HCT recipients survives to 1 year post-HCT Bone Marrow Transplant 47(3):337–341, 2012.
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without experiencing a major complication. The impact of newer Majhail NS: Secondary cancers following allogeneic haematopoietic cell
transplantation modalities, including the use of NMA or RIC regi- transplantation in adults. Br J Haematol 154(3):301–310, 2011.
mens, alternative donor transplantation with UCB, and incorporation McDonald GB: Hepatobiliary complications of hematopoietic cell transplan-
of immune-based therapies within transplantation regimens, on early tation, 40 years on. Hepatology 51(4):1450–1460, 2010.
and late complications are areas of current investigation. Better tools Panoskaltsis-Mortari A, Griese M, Madtes DK, et al: An official American
to predict the risk of post-HCT complications and nonrelapse Thoracic Society research statement: noninfectious lung injury after
mortality are needed as well. Genomic and proteomic approaches to hematopoietic stem cell transplantation: idiopathic pneumonia syndrome.
HCT complications are being investigated to monitor and predict Am J Respir Crit Care Med 183(9):1262–1279, 2011.
complications. Although they are some years from use in clinical Rizzo JD, Wingard JR, Tichelli A, et al: Recommended screening and preven-
practice, these approaches could have many potential applications in tive practices for long-term survivors after hematopoietic cell transplan-
transplantation, including prediction of risk for complications and tation: joint recommendations of the European Group for Blood and
GVHD, refining donor selection, and utilization of pharmacoge- Marrow Transplantation, the Center for International Blood and Marrow
nomic data to individualize conditioning regimens and immunosup- Transplant Research, and the American Society of Blood and Marrow
pression. Each of these facets represent areas of ongoing vigorous Transplantation. Biol Blood Marrow Transplant 12(2):138–151, 2006.
research to improve the safety and effectiveness of HCT. Rizzo JD, Curtis RE, Socie G, et al: Solid cancers after allogeneic hematopoi-
etic cell transplantation. Blood 113(5):1175–1183, 2009.
Sun CL, Francisco L, Baker KS, et al: Adverse psychological outcomes
SUGGESTED READINGS in long-term survivors of hematopoietic cell transplantation: a report
from the Bone Marrow Transplant Survivor Study (BMTSS). Blood
Alousi AM, Weisdorf DJ, Logan BR, et al: Etanercept, mycophenolate, 118(17):4723–4731, 2011.
denileukin, or pentostatin plus corticosteroids for acute graft-versus-host Sun CL, Francisco L, Kawashima T, et al: Prevalence and predictors of chronic
disease: a randomized phase 2 trial from the Blood and Marrow Transplant health conditions after hematopoietic cell transplantation: a report from
Clinical Trials Network. Blood 114:511, 2009. the Bone Marrow Transplant Survivor Study. Blood 116(17):3129–3139,
Armenian SH, Sun CL, Kawashima T, et al: Long-term health-related 2010; quiz 3377.
outcomes in survivors of childhood cancer treated with HSCT versus Tomblyn M, Chiller T, Einsele H, et al: Guidelines for preventing infec-
conventional therapy: a report from the Bone Marrow Transplant Sur- tious complications among hematopoietic cell transplantation recipients:
vivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS). a global perspective. Biol Blood Marrow Transplant 15(10):1143–1238,
Blood 118(5):1413–1420, 2011. 2009.