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2091 results in Hematology

Page 31 of 105

  • 7 - Stem cell infusion

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 31-33

  • Summary

    Autologous

    Stem cells are routinelycryopreserved with dimethyl sulfoxide (DMSO). These products are red bloodcell (RBC) depleted before cryopreservation and thawed at 37°C in a waterbath before infusion. They should be infused through standard 170-micron redblood cell filters.

    General reactions and response to infusion toxicity

    The infusion of hematopoieticstem cells may be associated with toxicities that are either specific tohematopoietic products or general to all blood product infusions. Thefollowing text provides a minimal guideline to the workup and management ofinfusional toxicities. Each anticipated toxicity is defined and a plan ofaction is outlined.

    Bleeding

  • Unprocessed marrow contains approximately 20 000 units of heparin, which is infused over 1 to 4 hours. h is will result in anticoagulation to a degree sui cient to result in clinical bleeding. Patients at risk are those with a history of recent surgery (e.g., recent line placement or revision), hemorrhagic cystitis, severe thrombocytopenia. However, bleeding can occur in any individual.

  • For a patient with a known hemorrhagic risk, the marrow should be concentrated and washed to remove heparin. If the risk factor is known before a harvest takes place, acid citrate dextrose (ACD) can be used in place of heparin as a cryopreservative, if allowed by protocol.

  • Infused heparin can be reversed with protamine. One mg of protamine will neutralize approximately 100 units of heparin. Maximum dose is 50 mg and the infusion rate should not exceed 5 mg/min .

  • 21 - Oral health in stem cell transplantation

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 130-153

  • Summary

    Introduction

    The oral cavity is a frequentsite of infectious and noninfectious complications during and after stemcell transplantation. Good dental hygiene before and after HSCT isimportant. Risk of developing complications is dependent on a number offactors, including pretransplant dental health, HSV seropositivity, age,graft source, conditioning regimen intensity, development ofgraft-versus-host disease (GVHD), and the need for long-termimmunosuppressive therapy. Patients should be routinely monitored for oralcavity changes and symptoms at all stages of transplantation.Transplantation programs can benefit greatly from the inclusion of oralmedicine as part of the care team, in particular for diagnosis andmanagement of patients with oral conditions of unclear etiology, or forthose that do not respond to standard first-line therapies.

    Pretransplant dental evaluation

    The dentition is a potentialsource of infection during transplantation and prolonged periods of profoundimmunosuppression. In order to reduce risk, all patients should undergo acomprehensive dental evaluation by a dentist prior to transplantation. Theevaluation should consist of a full mouth series of intraoral radiographsand hard and soft tissue examination with special attention to caries,defective restorations, mobile teeth and teeth with deep pocketing(periodontal disease), third molars, and periapical pathology (Figures 21.1and 21.2). All patients should receive a dental prophylaxis and any teethwith caries should be treated. Sharp edges should be smoothed to reduce riskof soft tissue injury which might contribute to mucositis. Teeth withperiapical pathology require endodontic therapy or extraction. Third molarswith a prior history of pericoronitis (infection/swelling of surroundinggingiva) should be considered for extraction (Figure 21.3). The foregoinginformation is summarized in Table 21.1.

  • 24 - Special transfusion-related situations

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 167-169

  • Summary

    A complete discussion oftransfusion reactions is beyond the scope of this manual. The incidence ofinfection through a blood transfusion has been greatly reduced, given theimprovements in donor screening and processing techniques. The mostsignificant infectious risk of transfusions is due to bacteriallycontaminated platelets. Platelets must be stored at room temperature and onan average 1 in 3000 bags are contaminated with bacteria proven by culture.The risk of an infection through a platelet transfusion is approximately 1in 20,000.

    Mechanism

    The risk oftransfusion-related acute lung injury (TRALI) is estimated at 1 case per5000 transfusions. It is characterized by acute onset of hypoxemia and theappearance of bilateral infiltration on chest X-ray within 6 hours oftransfusion of a plasma-containing product. The exact mechanism is unknown,but in a subset of patients donor antibodies (usually antiHLA) react withthe recipient’s white blood cells resulting in both release of intracellularinflammatory mediators and leukoagglutination in the lungs.

  • 5 - Pretransplant evaluation and counseling of patient and donor

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 15-20

  • Summary

    Pretransplant counseling

    Both patient and donor arecompletely evaluated before stem cell transplantation. The evaluation shouldcomply within guidelines established by the Food and Drug Administration(FDA), Foundation for the Accreditation of Cellular Therapy (FACT), andother regulations and should be available in written form specific to yourinstitution. Both patient and donor evaluations include a thorough historyand physical examination and a series of studies to confirm medicaleligibility.

    Treatment recommendationsshould be discussed thoroughly with the patient, donor, and family. Themarrow graft procedure as well as alternative forms of therapy, as far asthey exist, should be presented as objectively as possible. The risks andhazards of stem cell mobilization and the donation procedure and any otherprocedures associated with the donation must be explained to the donor aswell as to the patient or, in the case of minors, to the donor or patient’sresponsible family member. Plans for protection of fertility are alsodiscussed at this time. Reading material, videos, and other educational aidsare helpful and should be available. In addition, a discussion of patientwishes regarding aggressive supportive measures (i.e., cardiopulmonaryresuscitation, mechanical ventilation, other artificial means of lifesupport) and establishment of a living will or other advanced directivesshould be included in these discussions. It is important to point outspecifically that some aspects of hematopoietic stem cell transplantation(HSCT) are still considered experimental. We strongly recommend thatpatients undergo a psychosocial evaluation and that financial aspects of thetransplant are discussed with the patient and his/her family beforetransplantation.

  • 20 - Gastrointestinal complications

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 124-129

  • Summary

    Nausea/Vomiting

    Chemotherapy and/or radiationare typically emetogenic, and symptoms are expected early afterhematopoietic stem cell transplantation. Medications such as antibiotics,opioids, MMF, mepron, and others can also contribute to nausea and vomiting.Acute upper gastrointestinal (GI) graft-versus-host disease (GVHD) typicallymanifests as nausea and can only be reliably diagnosed by stomach biopsy.Infections with herpes simplex virus (HSV), cytomegalovirus (CMV),adenovirus, Helicobacter pylori, and fungus are commonoffenders and need to be treated specifically.

    Pattern

  • Acute onset occurs within 24 hours of chemotherapy administration (peak at 4–6 h) and lasts for 24 to 48 hours. Usually responds to drug therapy.

  • Delayed onset occurs more than 24 hours after chemotherapy administration (peak at 2–3 days) and can last for several days. Variable response to drug therapy – commonly seen with cyclophosphamide, anthracyclines, and cisplatin.

  • Delayed after engraftment, usually associated with weight loss; may be GVHD.

    • Diagnostic testing

  • Upper endoscopy with biopsy may be useful to assess for either GVHD or infectious etiologies.

    • Management

    It is preferable to prevent asmuch nausea and vomiting as possible since treatment of established nauseais more dii cult to manage. Moreover, prevention will decrease futureanticipatory, breakthrough, and delayed nausea/vomiting.

  • 12 - Overview of acute and chronic graft-versus-host disease

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 48-49

  • Summary

    Overview

    Graft-versus-host disease(GVHD) is one of the classical complications of allogeneic stem celltransplantation. It is dependent on the presence of histocompatibilitydifferences between the host and the donor. These can be minor antigens inthe case of matched transplantation or major histocompatibility complex(MHC) antigens if there is some human leukocyte antigen (HLA)incompatibility. Minor antigens are presented to the T cells presumably inthe same way that bacterial or viral antigens are presented. Thus, inessence, the graft is functioning as if there were a severe infection, andthe graft tries to eradicate antigens that are intrinsic to the host. Thisresults in the tissue damage that we clinically recognize as GVHD.

    There are two main categoriesof GVHD, acute and chronic, each with two subcategories:

    Acute GVHD

  • Classic acute GVHD.

  • Late-onset acute GVHD .

    • Chronic GVHD

  • Classic chronic GVHD.

  • Overlap GVHD, with features of both acute and chronic GVHD

    • Previously, acute GVHD (aGVHD)was arbitrarily assigned to all allogeneic manifestations that occurredbefore day 100, and cGVHD to those occurring at er day 100, but thisdistinction is no longer considered useful. It is now recognized that therecan be late-onset aGVHD (frequently but not exclusively afterreduced-intensity transplantation), and manifestations of cGVHD may occurbefore day 100.

  • 17 - Engraftment syndrome

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 101-102

  • Summary

    Engraftment syndrome is aninflammatory disorder that usually occurs within the first 2 weeks afterstem cell transplantation.

    Clinical manifestations

    Clinical manifestations may beassociated with high fevers, generalized erythrodermatous rash, andthird-spacing (explaining peripheral and noncardiogenic pulmonary edema).There may be cough, dyspnea, hypoxemia, multilobar pulmonary infiltrates, orother nonspecific findings.

    Diagnosis

    Diagnosis is one of exclusion.h ere is no test for it, but tests that may be undertaken to rule outalternative etiologies include cultures, skin biopsy, and bronchoalveolarlavage.

    Etiology

    Etiology is poorly understood.In general, it is thought to rel ect cytokine production due to immunedysregulation in the context of neutrophil recovery. Polymorphonuclearleukocytes (PMNs) and lymphocytes are thought to be activated and contributeto the injury through further production of inflammatory mediators.

    Differential diagnosis

  • Hyperacute graft-versus-host disease (GVHD) or traditional GVHD.

  • Infection: Patients should always be treated presumptively for infection while diagnostic studies and cultures are being carried out.

  • Transfusion-associated lung injury (TRALI). This entity typically occurs proximate to a transfusion and is thought to be due to preformed antiHLA antibodies in the transfused product.

  • Drug reaction.

  • 13 - Acute graft-versus-host disease and staging

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 50-52

  • Summary

    Acute graft-versus-hostdisease (GVHD) occurs when donor T cells recognize host antigens as foreign,resulting in T-cell lymphocyte stimulation (antigen presentation, T-cellactivation, and T-cell proliferation) and T-cell and secondary effector cellresponse (cytokine secretion, cytotoxic T cells, natural killer [NK] cells).Contribution of specific subsets remains uncertain. In murine systems, NKcells play a role in GVHD development. The development of acute GVHD (aGVHD)may be triggered by the initial tissue damage from the conditioning regimen,which releases inflammatory cytokines such as γ-interferon, IL-1, and tumornecrosis factor (TNF). Risk factors for aGVHD include disparity at class Ior class II HLA loci, female donor → male recipient, older patient age,older donor age, multiparous female donor, and herpes simplex virus (HSV) orcytomegalovirus (CMV) seropositivity. Patients who develop aGVHD are athigher risk for developing chronic GVHD (cGVHD).

    As noted earlier, aGVHD canbe classic or late-onset. Acute GVHD is characterized by skin,gastrointestinal (GI) tract, and/or hepatic involvement.

  • 18 - Infectious disease

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 103-120

  • Summary

    Risk factors for infectioninclude the degree and duration of neutropenia; profoundpan-immunosuppression; disruption of mucosal barrier by radiochemotherapy;HLA mismatch; central venous access; donor prior exposures; and especiallycord blood transplants. Inadequate immunoglobulin (especially IgG2 and IgG4)production increases risk of infection with encapsulated organisms despitetotal Ig levels in the normal range after transplant.

    Please see Chapter 22 forspecific pulmonary infections.

    General time frames of when infection is likely to occur

  • Days 0 to 30: Infections related to conditioning regimen and neutropenia (bacteremia of GI or catheter-related origin), invasive aspergillosis related to neutropenia, candidemia.

  • Days 30 to 80: Classic opportunistic infections (cytomegalovirus [CMV],Pneumocystis jiroveci pneumonia [PCP], toxoplasmosis, nocardiosis, invasive aspergillosis, and other invasive mold infections related to severe GVHD).

  • Day 180+: Encapsulated organisms (especially in patients with chronic GVHD), varicella zoster virus (VZV), PCP.

    • Figure 18.1 outlines theperiod of major host dei cits and infections that occur during allogeneicHSCT in relation to the deployment of targeted pathogen-specii cprophylactic, preemptive, and empiric therapies. Risk for infectiouscomplications is temporally dependent, and it may be signii cantly decreasedby prophylactic, preemptive, or empiric therapy. The risk of certaininfections after transplantation is highly associated with ongoingimmunologic manipulation as seen with the therapy for GVHD (Figure 18.1;linkages denoted by vertical arrows).

  • 29 - Transplantation: regulation and accreditation

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 181-181

  • Summary

    Governmental regulations existat both the federal and state level. At the federal level, the US Food andDrug Administration (FDA) is responsible for enforcing the regulations forhuman cells, tissues, and cellular- and tissue-based products. Cellularproducts are regulated under either cGTP 21CFR 1271, cGMP 21 CFR 210, or inpart under the device regulations. Cell therapy products that are more thanminimally manipulated (including all gene therapy products) most often needan FDA IND exemption and at least Institutional Review Board (IRB) approvalbefore use. Some states have developed licensure processes, certificateprograms, and so on, but other states have few specific regulations.

    There are three voluntaryprofessional organizations that set standards and accredit variouscomponents of hematopoietic stem cell transplantation (HSCT). The threefoundations are the Foundation for the Accreditation of Cellular Therapy(FACT), the American Association of Blood Banks (AABB), and the NationalMarrow Donor Program (NMDP).

    The Foundation for theAccreditation of Cellular Therapy is a partnership between twoorganizations, one based on clinical outcome while the other is laboratorybased. In concert, they provide minimal guidelines and standards to allsources and phases for facilities and individuals who perform HSCT. It isimportant to know your program’s specific regulations under FDA, state, andother voluntary accredited programs.

  • 28 - Donor lymphocyte infusion

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 179-180

  • Summary

    Donor lymphocyte infusion(DLI) is an effective method to induce graft-versus-leukemia (GVL) and iscommonly used to treat patients with hematologic malignancies who haverelapsed after allogeneic stem cell transplantation, or to treat patientswith falling donor chimerism after reduced-intensity conditioning. Previousreviews from Europe and North America have reported complete hematologic andcytogenetic response rates in over 75% of patients with stable-phase chronicmyelogenous leukemia (CML) treated with DLI following HSCT, althoughoutcomes are significantly worse in other hematologic malignancies.

    Induction of GVL

  • In patients who need DLI while still on immunosuppression, a rapid taper of immunosuppressants will often result in a GVHD flare that can induce remission or full chimerism.

  • In patients who are off all immunosuppression, DLI is a reasonable strategy to induce GVL.

    • Collection and administration of DLI

  • Lymphocytes are typically collected without filgrastim stimulation.

  • Cells can be used fresh; however, it is useful to cryopreserve cells in aliquots of 1 to 5 x 107 CD3+ cells/kg body weight.

  • For indolent diseases, administration of cells in gradually increasing numbers separated by 4 to 8 weeks will reduce the risk of GVHD. For instance, start with 1 x 107 CD3+ cells/kg. If there is no GVHD and the desired response has not been achieved by 6 weeks, increase the dose to 5 x 107 CD3+ cells/kg. Doses beyond 108 CD3+ cells/kg are usually not desirable.

  • For aggressive diseases, typical doses of 108 CD3+ cells/kg are administered as a single dose.

  • 2 - Types of transplantation

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 3-5

  • Summary

    Autologous transplantation

    Autologous stem celltransplantation (or stem cell rescue) allows the administration of high-dosechemotherapy or chemoradiotherapy and eliminates myelotoxicity as adose-limiting complication.

  • The stem cell source can be either mobilized peripheral blood stem cells or bone marrow.

  • Autologous transplantation is commonly used for lymphomas and myeloma and less commonly for leukemia.

  • Autologous transplantation is also used for testicular cancer.

  • In patients with leukemia and lymphoma, there is considerable concern over the reinfusion of occult tumor cells along with the marrow or peripheral blood progenitors. Therefore, numerous attempts to purge tumor cells from stem cells have been undertaken. However, it is unclear whether such manipulation affects relapse, and tumor purging is not routinely performed. Arguments against purging include its cost and labor intensiveness. Moreover, for lymphoma and solid tumors, relapse occurs usually at sites of prior bulky disease, suggesting that residual tumor within the recipient, not tumor in the stem cell product, is the primary contributor to relapse. Arguments in favor of purging include gene marking studies showing that marrow involvement can contribute to relapse.

    • Allogeneic transplantation

    Allogeneic transplantationuses stem cells from either a family member or an unrelated donor. Sourcesinclude bone marrow, peripheral blood, or umbilical cord blood.

  • Typically fully matched donors are preferred, but various degrees of incompatibility can be tolerated with appropriate attention to prevention of rejection and graft-versus-host disease (GVHD).

  • Haploidentical transplantation (from family members matched at one HLA haplotype, that is, potentially as few as 6/12 loci) is considered investigational.

  • Conditioning regimens vary in intensity and are categorized by the duration of cytopenia and on the requirement for stem cell support. There are three levels of intensity: nonmyeloablative (NMA), reduced-intensity conditioning (RIC), and high-intensity or myeloablative conditioning (MAC).

  • 6 - Conditioning regimens

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 21-30

  • Summary

    Conditioning regimens aredesigned to destroy tumor cells resistant to conventional doses ofchemotherapy without causing fatal nonhematologic organ toxicity. Inpatients undergoing allogeneic stem cell transplantation, conditioningregimens must be sufficiently immunosuppressive to prevent the recipientfrom mounting an immune response capable of rejecting the graft. Graftrejection is uncommon, but this complication is associated with a direoutcome and the risk increases with the degree of mismatch.

    There are few randomizedtrials comparing different ablative regimens; in general, increasedintensity of the conditioning regimen may decrease relapse rates, butusually (though not always) at the expense of increased nonrelapse morbidityand mortality. The following represent some of the more common regimens usedtoday, although different combinations and doses may be used at differentcenters. It is essential to check the specific protocol that applies to thepatient for drugs, doses, frequency, and other specifics of treatments.Biologic agents such as Campath® or antithymocyte globulin (ATG)may be added to enhance immunosuppression. See Appendix for ideal bodyweight (IBW) and adjusted ideal body weight (AIBW) for obese patients. Table6.1 summarizes currently used regimens.

  • 27 - Cystitis

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 177-178

  • Summary

    There are two main causes ofhemorrhagic cystitis in the transplant patient: conditioning regimen-relatedtoxicity and viral infection. Cystitis that occurs early (days 1 to 14) isusually caused by the conditioning agents, and is generally related tohigh-dose cyclophosphamide. The incidence of early cystitis is reduced withthe use of aggressive hydration with forced saline diuresis or theadministration of mesna for uroprotection. Mesna binds to an inactivemetabolite of cyclophosphamide, acrolein, preventing urothelialinflammation. Mesna is effective only during cyclophosphamidemetabolism/excretion, but not once hemorrhagic cystitis is established. Werecommend prehydration with 1000 mL of D5NS with 20 mEq/L of KCl at 500 mL/hfor at least 2 hours before cyclophosphamide, and maintenance of hydrationwith D5NS at 200 mL/h for 12 hours after cyclophosphamide using furosemideif necessary to maintain urine output >200 mL/h.

    Hemorrhagic cystitis occurringafter day 14 is usually due to a viral infection, the two most common beingBK virus and adenovirus.

  • 16 - Chronic graft-versus-host disease

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 79-100

  • Summary

    In the past, chronicgraft-versus-host disease (cGVHD) was characterized by time of onset.Generally speaking, any manifestation of GVHD after day 100 was termed cGVHD. The NIH Consensus Working Group data suggest thatclinical manifestations, and not the time to symptomatic onset aftertransplantation, determine whether the syndrome is acute or chronic. Inaddition, a new scoring/grading system replaces the historical system ofclassifying a patient as having “limited” or “extensive” disease.

    There is no consensusregarding the pathogenesis of cGVHD. T lymphocytes play a major role butevidence shows that in some patients there is coordinated B-cell and T-cellattack. In addition, some data suggest that cGVHD may be related toautoimmune reactions of the donor cells.

    Risk factors

    Accepted factors

  • history of grade II or higher acute GVHD (aGVHD);

  • disparity at class I or class II human leucocyte antigen (HLA) loci;

  • peripheral blood stem cells versus bone marrow source;

  • patient diagnosis (chronic myelogenous leukemia [CML] and aplastic anemia);

  • female donor ͢ male recipient (even greater if parous);

  • older recipient age;

  • multiparous female donor;

  • history of acute inl ammation (e.g., TEN, Stevens Johnson, and others);

  • non-T-cell-depleted source;

  • donor lymphocyte infusion (DLI);

  • sun exposure.

  • 11 - Transplant-related complications

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 47-47

  • Summary

    When making a differentialdiagnosis in a patient who has undergone hematopoietic stem celltransplantation (HSCT), it is critical to have a solid understanding of theentire course of treatment. This includes transplant type (autologous orallogeneic) including intensity of chemotherapy, stem cell source (marrow,peripheral blood [PB], or cord blood), donor match (related or unrelated,matched or mismatched), interval post-HSCT (early or late),graft-versus-host disease (GVHD) prophylaxis, infectious prophylaxis,current immune suppressive medications, and length of granulocytopenia.Transplant-related toxicities can include treatment-related organ damage,infection, GVHD, or any other combination. Time course is generallyconsidered as follows: early – first 30 days when pancytopenia and thedirect effect of chemotherapy is greatest; mild – day 15 to roughly day 100;and late – after day 100. There is often an overlap in timing ofcomplications.

    In the remainder of the bookyou will find information on the following transplant-relatedcomplications:

  • GVHD – prevention, acute and chronic;

  • engraftment syndrome;

  • infectious disease;

  • graft rejection and failure;

  • gastrointestinal complications;

  • oral care and complications;

  • pulmonary complications;

  • veno-occlusive disease;

  • special transfusion-related situations;

  • cardiovascular complications;

  • neurological complications;

  • cystitis;

  • donor lymphocyte infusion.

  • 19 - Graft rejection and failure

  • Joseph H. Antin, Deborah Yolin Raley
  • Book:
    Manual of Stem Cell and Bone Marrow Transplantation
    Published online:
    05 November 2013
    Print publication:
    17 October 2013, pp 121-123

  • Summary

    Graft rejection

  • Graft rejection refers to the immunologic rejection of donor hematopoietic elements by the residual host immune system. Graft rejection occurs more frequently in patients transplanted for aplastic anemia and in those receiving unrelated or mismatched transplants (because of increased donor–recipient disparity at major and minor HLA loci). Graft rejection may also be observed in reduced-intensity regimens, especially in patients who are not pretreated heavily.

  • In many patients with aplastic anemia, the underlying pathophysiology reflects an autoimmune recognition of the stem cells by an aberrant immune response. Most conditioning regimens used in aplastic anemia are reduced-intensity regimens. If the conditioning regimen does not fully eliminate the abnormal immune response, the graft may fail by the same mechanism that resulted in aplastic anemia in the first place. Prior to matched related donor transplantation, family member, directed donor transfusions should not be administered to avoid alloimmunization of the patient against minor histocompatibility antigens that are common to other family members.

Page 31 of 105