Hematopoietic Cell Transplantation Overview
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Questions and Answers

What term has become preferred for the process involving the collection and transplantation of various sources of hematopoietic stem cells?

  • Hematopoietic stem cell transfer
  • Hematopoietic cell transplantation (correct)
  • Stem cell infusion therapy
  • Bone marrow replacement therapy

    • Which feature of the hematopoietic stem cell is crucial for its successful transplantation?

  • Its regenerative capacity (correct)
  • Its role in immune response
  • Its preference for fatty tissue
  • Its ability to produce hormones

    • What advantage does allogeneic hematopoietic cell transplantation offer in the treatment of malignancy?

  • It allows for higher doses of myelosuppressive therapy (correct)
  • It guarantees a complete eradication of tumors
  • It eliminates the need for donors
  • It reduces the transplant rejection rates

    • What was the estimated number of hematopoietic cell transplants performed worldwide in 2020?

    <p>100,000 transplants</p> Signup and view all the answers

    What aspect of hematopoietic cell transplantation shows variation between countries?

    <p>Transplant rates and disease indications</p> Signup and view all the answers

    What characteristic enables hematopoietic stem cells to locate to the marrow space after being injected intravenously?

    <p>Their homing ability</p> Signup and view all the answers

    What is a consequence of the expanding donor availability for hematopoietic cell transplantation?

    <p>Increased safety and applicability for more diseases</p> Signup and view all the answers

    What effect does the immunologic graft-versus-tumor provide in the context of hematopoietic cell transplantation?

    <p>It enhances the effectiveness of tumor treatment</p> Signup and view all the answers

    What is the probability that a patient has an HLA-identical sibling if they have three siblings?

    <p>1/8</p> Signup and view all the answers

    Which of the following HLA genes are most relevant to transplantation?

    <p>HLA-A, HLA-B, HLA-C, HLA-D</p> Signup and view all the answers

    What is the typical risk of graft rejection using conventional techniques?

    <p>1-3%</p> Signup and view all the answers

    What role does posttransplant high-dose cyclophosphamide play in transplantation?

    <p>It reduces the need for HLA-matched donors.</p> Signup and view all the answers

    How does the incidence of GVHD change with the number of mismatched antigens?

    <p>It increases progressively with each mismatch.</p> Signup and view all the answers

    What is the estimated chance of any two unrelated individuals being HLA identical?

    <p>Approximately 1 in 10,000</p> Signup and view all the answers

    What percentage of patients can find HLA-matched donors when searching from a registry of over 30 million volunteer donors?

    <p>About 60%</p> Signup and view all the answers

    What is the impact on survival rates when comparing two or three-antigen mismatched transplants to HLA-identical transplants?

    <p>Survival rates are significantly reduced.</p> Signup and view all the answers

    What is the primary benefit of reduced-intensity conditioning regimens in transplantation?

    <p>They cause less significant myelosuppression compared to conventional regimens.</p> Signup and view all the answers

    Which of the following treatments is least likely to contribute to an effective GVT response?

    <p>T cell depletion of allogeneic marrow.</p> Signup and view all the answers

    What is the risk associated with high-dose treatment regimens for patients undergoing transplantation?

    <p>Higher associated transplant-related mortality for most patients.</p> Signup and view all the answers

    How does the development of GVHD impact relapse rates post-transplant?

    <p>Corresponds to the lowest relapse rates in transplanted patients.</p> Signup and view all the answers

    What is the significance of using nonmyeloablative regimens?

    <p>They can achieve engraftment with minimal toxicity.</p> Signup and view all the answers

    From which area of the body is marrow typically collected from the donor?

    <p>Posterior iliac crest.</p> Signup and view all the answers

    Which factor is most likely to lead to the decision to use high-dose regimens in certain patients?

    <p>Evidence of measurable disease at the time of transplantation.</p> Signup and view all the answers

    What volume of marrow is typically collected from a donor during the procedure?

    <p>10-15 mL/kg.</p> Signup and view all the answers

    What is the expected 5-year disease-free survival rate for patients who never achieve a first remission with standard chemotherapy and undergo transplantation?

    <p>20-30%</p> Signup and view all the answers

    For patients with myeloma, what factor has been shown to improve both disease-free survival and overall survival when included in initial therapy?

    <p>Autologous transplantation</p> Signup and view all the answers

    What treatment modality has yielded mixed results when combined with autologous transplantation for myeloma?

    <p>Nonmyeloablative allogeneic transplantation</p> Signup and view all the answers

    What is the approximate cure rate for patients with testicular cancer who are treated with high-dose chemotherapy and autologous stem cell support after first-line chemotherapy fails?

    <p>50%</p> Signup and view all the answers

    Which type of therapy has shown to yield better outcomes than low-dose salvage chemotherapy in patients with testicular cancer?

    <p>High-dose chemotherapy with autologous stem cell support</p> Signup and view all the answers

    What is a potential treatment option for patients who relapse following autologous transplantation with a long initial remission?

    <p>Allogeneic transplantation</p> Signup and view all the answers

    What is the primary outcome being studied for high-dose chemotherapy with autologous stem cell support in solid tumors?

    <p>Cure rate improvement</p> Signup and view all the answers

    What remains a significant factor for obtaining the best results with high-dose chemotherapy in solid tumors?

    <p>Sensitivity of the remaining tumor to chemotherapy</p> Signup and view all the answers

    What is the disease-free survival rate at 3 years for patients who achieved complete remissions, according to the content?

    <p>50%</p> Signup and view all the answers

    For whom is allogeneic transplantation generally reserved in cases of myelodysplasia?

    <p>Patients with an IPSS score of Int-2 or higher</p> Signup and view all the answers

    What is the reported 5-year progression-free survival rate for allogeneic hematopoietic cell transplantation in myelofibrosis?

    <p>65%</p> Signup and view all the answers

    What percentage of patients with disseminated intermediate- or high-grade non-Hodgkin's lymphoma can still be cured after first-line chemotherapy failure when transplanted?

    <p>40-50%</p> Signup and view all the answers

    What is the primary reason congenital anemias like Blackfan-Diamond anemia can be treated with transplantation?

    <p>Transplantation replaces the defective bone marrow.</p> Signup and view all the answers

    Which transplantation approach is typically favored for patients with intermediate- or high-grade non-Hodgkin's lymphoma?

    <p>Autologous transplantation due to fewer complications</p> Signup and view all the answers

    What benefit does early transplantation provide for patients with storage diseases?

    <p>It increases the chance of success before irreversible damage occurs.</p> Signup and view all the answers

    What is a potential outcome for patients with recurrent indolent non-Hodgkin's lymphoma after autologous transplantation?

    <p>High response rates but unclear role of transplantation</p> Signup and view all the answers

    In relation to Hodgkin's disease, how does the role of transplantation compare to that in non-Hodgkin's lymphoma?

    <p>The role of transplantation is similar in both conditions</p> Signup and view all the answers

    Which of the following conditions is most likely to be treated successfully with hematopoietic cell transplantation?

    <p>Acute myeloid leukemia in first remission</p> Signup and view all the answers

    What may be the timeline for the resolution of fibrosis after allogeneic hematopoietic cell transplantation?

    <p>Several months to resolve</p> Signup and view all the answers

    What factor is critical to consider for patients with acute myeloid leukemia before proceeding with transplantation?

    <p>The determination of their HLA type soon after diagnosis.</p> Signup and view all the answers

    What has been observed in patients with autoimmune disorders who also have hematologic malignancies when treated with transplantation?

    <p>In some cases, they are cured of both conditions.</p> Signup and view all the answers

    What is a notable recovery rate difference in allogeneic hematopoietic cell transplantation based on remission status for acute myeloid leukemia?

    <p>Best results when applied in first remission.</p> Signup and view all the answers

    For patients under 60 years old with unfavorable-risk acute myeloid leukemia, what treatment has shown a survival advantage?

    <p>Matched related donor transplantation.</p> Signup and view all the answers

    What is a common challenge faced in the treatment of storage diseases with transplantation?

    <p>Irregular success rates depending on the stage of disease.</p> Signup and view all the answers

    Study Notes

    Hematopoietic Cell Transplantation

    • Bone marrow transplantation is an original term, but hematopoietic cell transplantation (HCT) is the preferred generic term, encompassing peripheral blood and umbilical cord blood stem cells.
    • HCT replaces abnormal lymphohematopoietic cells with normal donor cells to correct nonmalignant or malignant conditions.
    • HCT enhances myelosuppressive therapy by higher doses, and also offers the immunologic graft-versus-tumor effect (GVTE).
    • The Center for International Blood and Marrow Transplant Research (CIBMTR) estimates ~100,000 transplants worldwide in 2020.
    • Transplant rates correlate with Gross National Income (GNI) per capita, yet wide disparities remain within similar GNI groups.

    Categories of Hematopoietic Cell Transplantation

    • Syngeneic: Uses identical twins; no GVHD risk.
    • Autologous: Using the patient's own stem cells; no GVHD, but no GVTE; risk of tumor cell contamination.
    • Allogeneic: Using cells from a non-identical donor. Donors and recipients are not genetically identical, potentially causing GVHD (donor cells attacking recipient). Risk of graft rejection also exists if immunosuppression is inadequate.
    • Matching for HLA (human leukocyte antigen) molecules plays a critical role in allogeneic transplantation.
      • HLA matching is done to prevent severe, life-threatening acute GVHD.
      • Matching between donors and recipients affects the probability of graft rejection and severe GVHD, with a greater risk of complication associated with mismatches.

    Hematopoietic Stem Cells

    • Stem cells possess remarkable regenerative capacity.
    • Stem cells migrate to the bone marrow after intravenous injection.
    • Stem cells can be cryopreserved.
    • A single stem cell can entirely replace the fully functional lymphohematopoietic system in an adult mouse.
    • Homing of stem cells to the marrow is influenced by interactions between CXCL12 (stromal cell-derived factor 1) and CXCR4 (chemokine receptor) on the stem cells and the marrow.
    • Interactions between selectins (E- and L-selectin) on bone marrow endothelial cells and integrins (VLA-4) on early hematopoietic cells influence marrow homing.
    • Stem cells can withstand freezing and thawing with minimal damage, enabling storage for later reinfusion.

    Transplant Preparative Regimen

    • The regimen eradicates the patient's disease and suppresses their immune system (alloHCT).
    • Regimens vary based on the specific disease and donor source.
    • In some cases, like severe combined immunodeficiency, no therapy may be required.
    • High-dose cyclophosphamide with antithymocyte globulin might be used for aplastic anemia.
    • Busulfan is frequently added with cyclophosphamide for thalassemia and sickle cell anemia.
    • Malignant disease treatments often combine alkylating agents, irradiation, or others.
    • Reduced-intensity conditioning regimens lower toxicity while retaining anti-tumor effects; more common in HCT now.

    The Transplant Procedure

    • Marrow is typically obtained from the donor's iliac crest under anesthesia.
    • The marrow is processed to remove fat and bone fragments.
    • Stem cells are stored in heparinized media.

    Complications

    • Early Direct Chemoradiotoxicities: Common side effects from high-dose regimens: nausea, vomiting, skin irritation. Can lead to hemorrhagic cystitis (cyclophosphamide), oral mucositis, hair loss, profound pancytopenia, and sinusoidal obstruction syndrome (SOS).
    • Graft Failure: Stem cell engraftment doesn't occur or is lost transiently in autologous or allogeneic transplantation due to insufficient stem cells, ex vivo damage, or myelotoxic treatment post-transplant.
    • Graft-Versus-Host Disease (GVHD): In allogeneic HCT, donor immune cells attack recipient, leading to acute symptoms (skin rash, diarrhea, liver issues) within the first three months. Chronic GVHD can develop months later.
    • Infection: High risk due to immunosuppression. Prophylaxis against fungal and viral infections (e.g., CMV) is crucial.
    • Other potential complications: Autoimmune disorders, thyroid dysfunction, cataracts, and aseptic necrosis are also possible.

    Patient Selection and Outcomes

    • Factors associated with increased GVHD risk include HLA mismatches, higher intensity regimens, donor characteristics, and age of recipient and donor

    • Outcomes vary significantly depending on the disease, donor-recipient match, intensity of conditioning, and patient characteristics.

    Other Considerations

    • Risk of GVHD is higher when HLA-matching is not perfect.
    • The success of HCT is higher for younger patients with aggressive diseases.
    • HCT may involve removing isoagglutinins or incompatible red blood cells, depending on the mismatch, and possible removal of malignant cells
    • Improvement in HLA typing and supportive care correlates to similar survival to matched siblings in unrelated transplants.

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    Hematopoietic Cell Transplantation PDF

    Description

    Explore the complexities of hematopoietic cell transplantation (HCT), including its definitions, categories, and global statistics. Understand different types like syngeneic, autologous, and allogeneic transplants, as well as their benefits and risks. This quiz covers crucial aspects for those interested in transplant medicine and research.

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