Interventional procedure consultation document

Hand allotransplantation

Hand transplantation

Individuals whose hands have been severely damaged by injury or disease may undergo amputation. This procedure involves transplanting a hand from a recently deceased donor to the amputated stump. The donor bones are rigidly fixed to those of the patient and the blood vessels, nerves, tendons and skin are restored.

The National Institute for Health and Clinical Excellence (NICE) is examining hand allotransplantation and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about hand allotransplantation.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the provisional recommendations
• the identification of factual inaccuracies
• additional relevant evidence, with bibliographic references where possible.

Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).

NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved. NICE reserves the right to summarise and edit comments received during consultations, or not to publish them at all, where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

Closing date for comments: 23 November 2010

Target date for publication of guidance: February 2011

1   Provisional recommendations

1.1  Current evidence on the efficacy and safety of hand allotransplantation is inadequate in quantity. Therefore this procedure should only be used with special arrangements for clinical governance, consent and research.

1.2  Clinicians wishing to undertake hand allotransplantation should take the following actions.

• Inform the clinical governance leads in their Trusts.
• Ensure that patients and their carers understand the uncertainty about the procedure’s safety and efficacy, in particular the need for and risks of long-term immunosupression, and the fact that functioning of the transplant may be both delayed and limited. Patients should also be provided with clear written information. In addition, the use of NICE’s information for patients (‘Understanding NICE guidance’) is recommended (available from www.nice.org.uk/IPGXXXpublicinfo). [[details to be completed at publication]]

1.3  Hand allotransplantation should only be carried out in units with surgical teams experienced in limb transplantation and with appropriate experts in transplantation medicine. Patients’ suitability for hand allotransplantation should be carefully assessed, and alternative methods of management should be discussed, as well as appropriate rehabilitation.

1.4  Clinicians should submit data to the International Registry on Hand and Composite Tissue Transplantation (www.handregistry.com) and Transplant UK.

1.5  Further research into hand allotransplantation should include data on long-term functional outcomes, and any occurrence of malignancy associated with long-term immunosuppression should be published. NICE may review this procedure on publication of further evidence.

2   The procedure

2.1  Indications and current treatments

2.1.1  Amputation of an extremity may result from trauma or from surgery carried out to control pain or a disease process in the affected limb, such as malignancy or gangrene. The usual way of restoring some hand function after amputation of the arm is to fit a prosthesis. It may be possible to reimplant the hand after traumatic amputation.

2.2  Outline of the procedure

2.2.1  Hand allotransplantation aims to provide a hand that looks more natural than a mechanical prosthesis, and which restores some sensation and movement.

2.2.2  Before the procedure, psychological assessment is required of a patient’s motivation and likely compliance with postoperative rehabilitation and immunosuppressive medication.

2.2.3  A cadaveric limb removed surgically from a donor, below the elbow, is used for the transplant. Its suitability for the recipient is assessed by basic matching for sex, size, appearance, and sometimes genetic matching.

2.2.4  Hand allotransplantation is carried out with the patient under general anaesthesia, which may be supplemented by a regional nerve block. A tourniquet may be used for haemostasis. The radius and ulna from the donor limb are fixed to those of the recipient using intramedullary pins or plates. Arteries and veins are anastomosed using standard techniques. The major nerves are repaired and others are joined if possible. Tendons are repaired either individually or in groups.

2.2.5  Following the procedure the limb may be immobilised in a plaster splint for a number of weeks. The patient should undergo intensive rehabilitation, including physiotherapy, occupational therapy and possibly electrostimulation for best restoration of function. Long-term immunosuppression is needed to reduce the possibility of rejection.

Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/guidance/IP/844/overview

2.3   Efficacy

2.3.1  A case series of 30 patients (38 hands) reported that more than 70% of patients had improved quality of life following hand allotransplantation and that ‘most’ patients returned to work (absolute figures and follow-up not stated).

2.3.2  The case series of 30 patients (38 hands) reported 100% (37/37) graft survival at 1- and 2-year follow-up; however, graft failure occurred later in 10 hands due to non-compliance with the immunosuppression regimen (timing not stated). Acute rejection episodes occurred in 85% of patients within the first year; all episodes were reversed when promptly reported and treated.

2.3.3  A case report of 1 patient (1 hand) described re-amputation of the transplanted hand after 12 hours because of a large clot in the radial artery distal to the entry site of a cannula in the donor arm. A case report of 5 patients (5 hands) reported re-amputation of 1 hand at 9-month follow-up because of intractable ischaemia.

2.3.4  The case series of 30 patients (38 hands) reported that 90% of patients achieved tactile sensibility and 72% developed discriminative sensibility at follow-ups ranging from 6 months to 9 years (absolute figures not stated).

2.3.5  A case report of 5 patients (5 hands) reported an ‘excellent’ functional outcome in 1 patient, intrinsic muscle recovery in another patient, good function but no intrinsic muscle recovery in 2 patients, and good early progress in the remaining patient (2-month to 10‑year follow-up).

2.3.6  The Specialist Advisers listed key efficacy outcomes as hand function, rejection-free survival and patient satisfaction.

2.4   Safety

2.4.1  Arterial thrombosis and venous thrombosis each occurred in 1 of 37 procedures in the case series of 30 patients (38 hands); both patients required additional surgery (timing of events not stated).

2.4.2  Multiple arteriovenous fistulae requiring additional surgery were reported in 1 of 37 procedures in the case series of 30 patients (38 hands) (timing of events not stated).

2.4.3  Indolent (marginal zone) lymphoma was reported in 1 patient in the case report of 5 patients (5 hands) (follow-up ranged from 2 months to 10 years).

2.4.4  The case series of 30 patients (38 hands) reported opportunistic infections in 65% of the 29 patients receiving immunosuppression at follow-ups ranging from 6 months to 9 years. These included cytomegalovirus reactivation, cutaneous mycosis, herpes virus and Clostridium difficile. Most infections resolved with treatment.

2.4.5  The case series of 30 patients (38 hands) reported that metabolic complications related to immunosuppression therapy occurred in 52% (15/29) of patients at follow-ups ranging from 6 months to 9 years. These included transient hyperglycaemia, increased creatinine and Cushing’s syndrome.

2.4.6  The Specialist Advisers stated that adverse events reported in the literature include acute and chronic rejection (when immunosuppression was stopped), poor neurological function of the hand and immunosuppression-induced diabetes. They considered theoretical adverse events to include malignant changes or tumour development and graft–versus–host disease.

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

October 2010

_{Personal data will not be posted on the NICE website. In accordance with the Data Protection Act names will be anonymised, other than in circumstances where explicit permission has been given.}

 _{It is the responsibility of consultees to accurately cite academic work in order that they can be validated.}