(Contra) Indications - Bone Marrow Transplant

Indications - Allogeneic

I.


Histocompatibility - All potential allogeneic transplant recipients must have a five of six HLA antigen matched related or unrelated donor. The recipient and donor must be HLA-DR identical. Also, all unrelated donor/recipients must be HLA-DR Beta 1 identical by DNA analysis.

II. Type of Transplant by Disease Category

A. Related, Matched (myeloablative and non-myeloablative)
1. Acute Non-lymphocytic Leukemia in 1st, 2nd or greater remission
2. Refractory Acute Non-lymphocytic Leukemia (Considered on a case by case basis)
3. Acute Non-lymphocytic Leukemia in early relapse (<30 blasts)
4. Acute Lymphocytic Leukemia in 1st, 2nd or greater remission (adult) and Acute Lymphocytic Leukemia in 2nd or greater remission (children)
5. Chronic Myelogenous Leukemia in chronic or accelerated phase
6. Chronic Myelogenous Leukemia in 2nd chronic phase (after blast crisis)
7. Chronic Lymphocytic Leukemia - symptomatic advanced Stage III and IV
8. Juvenile Chronic Myelogenous Leukemia
9. Myelodysplasia
10. Hodgkin's Disease or Non-Hodgkin's Lymphoma
11. Aplastic Anemia
12. Multiple Myeloma
B. Unrelated, Matched
1. Acute Non-lymphocytic Leukemia in 1st, 2nd or greater remission (adult) and Acute Non-lymphocytic Leukemia in 2nd or greater remission (children)
2. Acute Non-lymphocytic Leukemia in early relapse (<30% blasts)
3. Acute Lymphocytic Leukemia in 2nd or greater remission
4. Chronic Myelogenous Leukemia in chronic or accelerated phase
5. Myelodysplasia (Refractory Anemia with Excess Blasts)
III. Source of progenitor cells
A. Bone Marrow
B. Peripheral blood stem cells
C. Cord blood


Indications - Autologous

I.


Disease Status - All patients must demonstrate chemotherapy responsive disease prior to autologous transplantation and evidence of normal cellular, malignancy - free bone marrow on marrow aspirate and biopsy. Peripheral blood stem cells will be the primary source of progenitor cells for autologous transplantation.
II. Diagnoses (Adults and Children)
A. Advanced Stage, Recurrent Hodgkin's Disease; non-purged
B. Advanced Stage, Recurrent Intermediate and/or High Grade, Non-Hodgkin's Lymphoma; non-purged
C. Low Grade Non-Hodgkin's Lymphoma, non-purged (adult)
D. Acute Nonlymphocytic Leukemia in 1st, 2nd or greater remission; non-purged (adults only)
E. Acute Nonlymphocytic Leukemia in 1st remission; purged (children only)
F. Neuroblastoma; purged and non-purged (adult and children)
G. Multiple Myeloma
H. Selected Solid Tumors
III. Source of Progenitor cells
A. Peripheral blood stem cells
B. Bone marrow with or without peripheral blood stem cells


Contraindications

I. Relative
A. Age
B. Cardiopulmonary Disease
C. Renal Disease
D. Liver Disease
E. Active Infection
F. Psychosocial dysfunction
II. Absolute
A. HIV seropositivity
B. Chronic Active Hepatitis
C. Any active soft tissue infection
D. Inability to give informed consent


Allogeneic and Autologous Eligibility Criteria

Adults and Adolescents (Allogeneic)

Patients must be >12 years but < 60 years of age for related donor transplants, and >12 years but < 60 years of age for non-related donor transplants, and < 75 years for non myeloablative, related donor transplant.

Patients must have an ECOG Performance Status of 2 or less.

Patients must have no evidence of active infection at the time of transplantation.

Patients must be HIV nonreactive.

Patients must have a multi-organ assessment prior to transplantation with the following outcome:

A resting ejection fraction of 50% or greater which increases with exercise as demonstrated by Resting/Exercise MUGA

A diffusion capacity of 50% or greater of predicted, a FEV1 of 60% or greater, and PO2 of 80 mm Hg as demonstrated on pulmonary functions testing

A serum creatinine of less than or equal to 2.0 mg/dL and a creatinine clearance of 50 ml/min or greater on 24 hr. urine collection

A total bilirubin of <2.5 mg/dL and/or a AST <2 times the upper limit of normal.

Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse are ineligible.

Patients who have any active infection such as a soft tissue infection, sinus infection, dental infections, fungal infections or hepatitis including chronic active hepatitis are ineligible; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date.

Patients who have diabetes mellitus will be considered on a case-by-case basis. However, patients with diabetes who are not controlled by medical management will be ineligible.

Psychosocial assessment by the bone marrow transplant team may identify individuals for whom this form of therapy may be contraindicated. These decisions will be based upon estimated adequacy of patient support systems and prediction of patient's compliance with medications, required diagnostic procedures and/or follow-up care.

Patients or their guardians must give written informed consent in accordance with institutional and federal regulations.

Patients or their guardians must demonstrate proof-of-payment.

Small Children and Infants (Allogeneic)

Patients must be <12 years of age for related donor transplants, and >1year but <12 years of age for non-related donor transplants.

Patients must have an ECOG Performance Status of 2 or less, or appropriate for age.

Patients must have no evidence of active infection at the time of transplantation.

Patients must be HIV non-reactive.

Patients must have a multi-organ assessment before transplantation with the following outcome:

A normal echocardiogram

O2 saturation >95% by pulse oximetry

A serum creatinine within normal limits for age

Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse are ineligible.

Patients who have any active infection such as a soft tissue infection, sinus infection, dental infections, fungal infections or hepatitis including chronic active hepatitis are ineligible; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date.

Patients who have diabetes mellitus will be considered on a case-by-case basis. However, patients with diabetes who are not controlled by medical management will be ineligible.

Guardian must give written informed consent in accordance with institutional and federal regulations.

Guardian must demonstrate proof-of-payment.

Adults and Adolescents (Autologous)

Patients must be ≥12 years but ≤ 70 years of age.

Patients must have a life expectancy without therapy of >4 weeks.

Patients must have an ECOG Performance Status of 2 or less, or appropriate for age.

Patients must have no evidence of active infection at the time of transplantation.

Patients must be HIV non-reactive.

Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater that the risk of relapse are ineligible.

Patients must have a multi-organ assessment before to transplantation with the following outcome:

A resting ejection fraction of 45% or greater which increases with exercise as demonstrated by Resting/Exercise MUGA with no documented coronary artery disease, history of congestive heart failure, or uncontrolled cardiac dysrhythmia.

A PO2 greater than 60% on room air, O2 saturation of greater than 90% on room air, a FEV1 of greater than 50% and diffusion capacity greater than 40% of predicted.

A serum creatinine of less than 2.0 mg/dL and a creatinine clearance of 50 ml/min or greater on 24 hr. urine collection.

A total bilirubin <2.5 mg/dL, AST<3 times normal.

Patients who have diabetes mellitus will be considered on a case-by-case basis. However, patients with diabetes who are not controlled by medical management will be ineligible.

Psychosocial assessment by the bone marrow transplant team may identify individuals for whom this form of therapy may be contraindicated. These decisions will be based upon estimated adequacy of patient support systems and prediction of patient's compliance with medications, required diagnostic procedures and/or follow-up care.

Patients or their guardians must give written informed consent in accordance with institutional and federal regulations.

Patients or their guardians must demonstrate proof-of-payment.

Small Children and Infants (Autologous)

Patients must be > 3 months but < 18 years of age at time of diagnosis.

Patients must have no evidence of active infection at the time of transplantation.

Patients must be HIV non-reactive.

Patients must have a multi-organ assessment before transplantation with the following outcome:

A normal echocardiogram

O2 saturation >95% by pulse oximetry

A serum creatinine within normal limits for age

Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse are ineligible.

Patients who have any active infection such as a soft tissue infection, dental infections, fungal infections or hepatitis including chronic active hepatitis are ineligible; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date.

Patients who have diabetes mellitus will be considered on a case-by-case basis. However, patients with diabetes who are not controlled by medical management will be ineligible.

Guardian must give written informed consent in accordance with institutional and federal regulations.

Guardian must demonstrate proof-of-payment.

Indications and Contraindications for Retransplantation

Allogeneic

Related Donor - Patients who have a related donor are eligible for a second allogeneic bone marrow transplant if they do not demonstrate evidence of engraftment or if graft failure occurs due to rejection or graft versus host disease. Patients must not have evidence of overwhelming infection or end-stage organ dysfunction.

Unrelated Donor - Patients who have an unrelated donor transplant are eligible for a second unrelated donor transplant if they do not demonstrate evidence of engraftment or if graft failure occurs. However, our Bone Marrow Transplant Program must abide by the retransplantation policy and procedures of the National Marrow Donor Program. Those patients who experience a recurrence of their disease following allogeneic bone marrow transplantation will be eligible for a second transplant if they are greater than six months from the first transplant, (first transplant which included ablative chemotherapy alone or in combination with radiotherapy), and if the status of their disease (malignancy only) is minimal or a remission has been achieved with salvage therapy. In addition, patients must have no evidence of major organ dysfunction and/or evidence of active infection. Each patient will be considered by the transplant team on a case-by-case basis.

Autologous

It is not our policy to perform second autologous transplants for patients with recurrent disease.

At this time, we do not perform tandem transplants, however, we do participate in an ECOG study that investigates the efficacy of tandem transplants for patients with testicular cancer.

Evaluation

Patient

A transplant physician in the outpatient clinic evaluates all patients considered for bone marrow transplantation. This evaluation consists of a review of medical records, pathology slides and x-ray films to determine medical history, diagnosis, stage (if applicable) and current disease status. Prior to transplantation, a multi-organ assessment is performed to demonstrate there are no contraindications to transplantation. Appropriate consultations are obtained when indicated. In addition, all transplant candidates and family members are interviewed by the transplant coordinator, primary outpatient nurse and social worker.

Donor

Potential donors are HLA-A, B and DR typed in addition to ABO typing. State- of-the-art, molecular, DR typing is also performed. All HLA testing must be performed at UWHC. Prior to transplantation, the potential donor must have an evaluation which includes: 1) complete history and physical; 2) CBC with differential and platelet count; 3) prothrombin time (PT) and partial thromboplastin time (PTT); 4) chemistry panel that includes glucose, electrolytes, and liver and renal function tests; 5) antibody screen for Hepatitis B and C; 6) antibody screen for toxoplasmosis, Epstein-Barr virus, RPR, HTLV I/II, cytomegalovirus and HIV antigen and antibody; 7) urinalysis. Other tests may be ordered when necessary, such as chest x-ray, electrocardiogram, and pregnancy test.

Also, adult donors may donate one unit of blood for autologous transfusion if it is planned that more than 500 ml of bone marrow will be collected. Donors who are minors will be evaluated on an individual basis regarding the necessity of transfusion following the marrow collection and/or the feasibility of their donating blood for autologous transfusion.

A detailed list of tests performed during the evaluation follows the Summary Statistics.

Acceptance

Patients are accepted/rejected as transplant candidates after the transplant team, which is comprised of transplant physicians, nurses, coordinators and social worker, reviews the initial evaluation. Patients who are accepted for transplantation must satisfy UWHC's financial requirements through written confirmation of insurance coverage or alternative financial arrangements.

When patients are not accepted for transplantation, either because they do not meet the indications or have a condition, which is contraindicated, the transplant physician informs them. When necessary, support from a social worker is available. In addition, we communicate information regarding non-acceptance to the appropriate referring or primary physician to whom the patient is referred back for continuing medical care.