ETHICAL ISSUES IN HSCT

Dr Obiageli E. NnoduConsultant Haematologist

University of Abuja Teaching Hospital.

Outline◦ Ethical issues involved in setting up the system-

1.Source,

2.Registries/banks,

3. Service providers,

4.Use of the resource

• Ethical issues involved in the transplant process

1.Recipient- eligibility, autonomy, conscious consent

2.Service providers- clinical integrity, end of life issues, moral distress and compassion fatigue

3.Institutional policies

• Summary

EthicsDraw parallels-

◦Medical Ethics – To protect the patient

◦Research Ethics – To protect the study participants, the community; and the scientist

◦Ethics of Scientific Practice – protects the “integrity” of the scientific process

◦All that is done in HSCT should be guided by the ethical principles of respect, autonomy, maleficence and beneficence with the best interest of the patient and donor at all times.

The Source◦Haemopoeitic stem cells can be sourced from the bone marrow, peripheral blood

and umbilical cord blood.

• Donor consent after full disclosure of procurement process, including inherent risks. Protocols in place

• Donors should be recognized and appreciated for their role.

• How do you communicate to potentials donors that they are not a match?

◦Donor safety (BMSC- infection, bleeding, pain. PBSC – risk of injection of growth factors to mobilize stem cells.)

◦ Ethical issues around IVF with PIGD (pre-implantation genetic diagnosis) to get HLA compatible embryo to be used for a sibling in need of an allograft. ???Other normal HLA incompatible embryos.

◦ Fairness. People contributing a resource should also be “allowed” to use it.

Registries/Cord Banks• No inducement nor incentive to donate

• Privacy of donors ensured (Socially acceptable deferral mechanism present stigmatization, also in reporting of results of safety tests)

• Cultural sensitivity in collection and storage of cord blood.

• Cord blood not for autodedication to pursue cures of MI, Alzheimers etc.

Caregivers◦ Properly trained care givers, multi-displinary team to include bioethicist who will

provide ethics consult when needed.

◦ Promote environment that allows team members to share concerns

◦Have protocols in place

◦Care conference, care agreement, agree in advance what to do before treatment starts

◦ Include “what if”

◦Have an institutional policy on end of life issues and how to handle it

Who should be transplanted◦ Fairness

◦ Privileged access?

◦ Set of criteria for malignant and benign haematology but the recipient should be able to :

1.Understand what is being done

2.Have physical, psychological coping abilities

3.Supportive family

◦Who enrolls the patient? – competence, knowledge and authority

Original Article Allogeneic Hematopoietic Stem-Cell

Transplantation for Sickle Cell Disease

Matthew M. Hsieh, M.D., Elizabeth M. Kang, M.D., Courtney D. Fitzhugh, M.D., M. Beth Link, R.N., Charles D. Bolan, M.D., Roger Kurlander, M.D., Richard W. Childs,

M.D., Griffin P. Rodgers, M.D., Jonathan D. Powell, M.D., Ph.D., and John F. Tisdale, M.D.

N Engl J MedVolume 361(24):2309-2317

December 10, 2009

Study Overview

• A modified conditioning protocol for allogeneic hematopoietic stem-cell transplantation that does not ablate the bone marrow was used to treat 10 adults who had severe sickle cell disease

• The sickle cell phenotype was eliminated in 9 of the 10 recipients

• No deaths, no major adverse events, and no graft-versus-host disease occurred among the recipients

Characteristics of 10 Patients Undergoing Nonmyeloablative Hematopoietic Stem-Cell Transplantation (HSCT)

Hsieh MM et al. N Engl J Med 2009;361:2309-2317

Overall survival: 93.1%EFS: 86.1%

Cumulative incidence of rejection: 70% at 5 years

The estimated 5-year TRM was 6.9%;

GVHD was the major cause of TRM

HSCT is a plausible standard of care for SCD children who are at high risk of stroke

Cerebral vasculopathy was the principle indication for transplantation (N = 55)

The role of HSCT in stroke prevention: the French experience

Bernaudin F, et al. Blood. 2007;110:2749-56.

EFS = event-free survival; GVHD = graft-versus-host disease;OS = overall survival; RM = transplantation-related mortality.

0

0.2

0.4

0.6

0.8

1.0

0 5 10 15

OSEFSRejection

Time (years)

Hematopopietic Stem Cell Transplantation in SCD◦HSCT remains the only curative modality

◦ Results after myeloablative conditioning are excellent in children with HLA identical sibling donors◦ 93 - 97% survival◦ 82 - 86% EFS

◦ Results in adults are not quite good

◦ Recent findings of success with non-myeloablative conditioning is improving outlook

◦ There is preferential survival of donor cells such that stable chimerism ensures satisfactory Hb levels post-HSCT

Who should be transplanted◦ Fairness

◦ Privileged access?

◦ Set of criteria for malignant and benign haematology but the recipient should be able to

1.Understand what is being done

2.Have physical, psychological coping abilities

3.Supportive family

◦Who enrolls the patient? – competence, knowledge and authority

Ethical Considerations◦ Respect

◦ Autonomy

◦ Beneficence

◦Non Maleficence

◦ Futility

◦ Benefit /Burden

◦Conscious consent

How do you communicate to a patient the risk of a procedure which has every chance of harm 25% mortality,21.5% chance of GVHD, ie it can kill you or make you ill for a long time but presents a good probability of cure

http://www.youtube.com/playlist?list=FLaffVkcOyEVrOT4dk1w3HBA

Ethical considerationsDoes HSCT satisfy these criteria?

a.One ought not to inflict harm

b.One ought to prevent evil or harm

c.One ought to remove evil or harm

d.One ought to promote the good. William Fraikena

“The patient has a right to refuse any kind of trial or therapy without having to provide any justification”- George Surbled

Consciousness◦Good communication between patient and physician

◦ Patients must know their overall medical condition

◦ Benefits of HSCT

◦ Risks vigorously stressed (60% effective 40% failure rate).

◦ Patient should be given time to think, understand, digest the possible outcome of HSCT in relation to conventional treatment.

◦Discrepancy between physicians and patients in terms of risk. Patients with advance disease fail to recognize the higher risks associated with their condition.

◦ This bias in the perception of risk can lead the patient to misunderstand the advantages and disadvantages of HSCT

◦Current suicidal ideations 82% 85% 89% 85% 0.45

◦Current use of addictive/illicit drugs 86% 80% 82% 84% 0.80

◦

◦History of non-compliance 68% 83% 79% 75% 0.20

◦

◦ Living far away, no caregiver 64% 67% 71% 68% 0.71

◦

◦ Patient told he is alcoholic 64% 66% 65% 60% 0.87

◦

◦Mild dementia (early Alzheimer’s) 27.3% 68% 63.5% 52% <0.001

Clinical Integrity◦ Patient autonomy balanced by physician integrity

◦ Physicians have no obligation to provide care that has no chance of success when patients request a particular treatment.

◦Clinicians must consider whether it is appropriate for them to provide it

◦Clinicians can refuse to agree with patient requests that involve treatment outside their range of expertise.

Summary

◦The practice of HSCT poses a number of ethical challenges. Those providing care should ensure that they do so under the fundamental principles of fairness, respect for patient autonomy, always acting in the best interest of the patient.

◦There is need to develop capacity to have bioethics consults to resolve ethical issues.