Leukemia
Types
Leukemia is classified by how quickly it progresses. Acute leukemia is fast-growing and can overrun the body within a few weeks or months. By contrast, chronic leukemia is slow-growing and progressively worsens over years.
Acute versus Chronic Leukemia The blood-forming (hematopoietic) cells of acute leukemia remain in an immature state, so they reproduce and accumulate very rapidly. Therefore, acute leukemia needs to be treated immediately, otherwise the disease may be fatal within a few months. Fortunately, some subtypes of acute leukemia respond very well to available therapies and they are curable. Children often develop acute forms of leukemia, which are managed differently from leukemia in adults.
In chronic leukemia, the blood-forming cells eventually mature, or differentiate, but they are not "normal." They remain in the bloodstream much longer than normal white blood cells, and they are unable to combat infection well.
Myelogenous versus Lymphocytic Leukemia Leukemia also is classified according to the type of white blood cell that is multiplying - that is, lymphocytes (immune system cells), granulocytes (bacteria-destroying cells), or monocytes (macrophage-forming cells). If the abnormal white blood cells are primarily granulocytes or monocytes, the leukemia is categorized as myelogenous, or myeloid, leukemia. On the other hand, if the abnormal blood cells arise from bone marrow lymphocytes, the cancer is called lymphocytic leukemia.
Other cancers, known as lymphomas, develop from lymphocytes within the lymph nodes, spleen, and other organs. Such cancers do not originate in the bone marrow and have a biological behavior that is different from lymphocytic leukemia.
There are over a dozen different types of leukemia, but four types occur most frequently. These classifications are based upon whether the leukemia is acute versus chronic and myelogenous versus lymphocytic, that is:
Acute Myelogenous (granulocytic) Leukemia (AML)
Chronic Myelogenous (granulocytic) Leukemia (CML)
Acute Lymphocytic (lymphoblastic) Leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)
Acute Myelogenous Leukemia (AML) Acute myelogenous leukemia (AML) - also known as acute nonlymphocytic leukemia (ANLL) - is the most common form of adult leukemia. Most patients are of retirement age (average age at diagnosis = 65 years), and more men are affected than women. Fortunately, because of recent advances in treatment, AML can be kept in remission (lessening of the disease) in approximately 60% to 70% of adults who undergo appropriate therapy. Initial response rates are approximately 65-75% but the overall cure rates are more on the order of 40-50%.
AML begins with abnormalities in the bone marrow blast cells that develop to form granulocytes, the white blood cells that contain small particles, or granules. The AML blasts do not mature, and they become too numerous in the blood and bone marrow. As the cells build up, they hamper the body's ability to fight infection and prevent bleeding. Therefore, it is necessary to treat this disease within a short time after making a diagnosis. AML, particularly in the monocytic M5 form, may spread to the gums and cause them to swell, bleed, and become painful. AML also may metastasize (spread) to the skin, causing small colored spots that mimic a rash.
Acute leukemia, such as AML, is categorized according to a system known as French-American-British (FAB) classification. FAB divides AML into eight subtypes:
undifferentiated AML (M0) - In this form of leukemia, the bone marrow cells show no significant signs of differentiation (maturation to obtain distinguishing cell characteristics).
myeloblastic leukemia (M1; with/without minimal cell maturation) - The bone marrow cells show some signs of granulocytic differentiation.
myeloblastic leukemia (M2; with cell maturation) - The maturation of bone marrow cells is at or beyond the promyelocyte (early granulocyte) stage; varying amounts of maturing granulocytes may be seen. This subtype often is associated with a specific genetic change involving translocation of chromosomes 8 and 21.
promyelocytic leukemia (M3 or M3 variant [M3V]) - Most cells are abnormal early granulocytes that are between myeloblasts and myelocytes in their stage of development and contain many small particles. The cell nucleus may vary in size and shape. Bleeding and blood clotting problems, such as disseminated intravascular coagulation (DIC), are commonly seen with this form of leukemia. Good responses are observed after treatment with retinoids, which are drugs chemically related to vitamin A.
myelomonocytic leukemia (M4 or M4 variant with eosinophilia [M4E]) - The bone marrow and circulating blood have variable amounts of differentiated granulocytes and monocytes. The proportion of monocytes and promonocytes (early monocyte form) in the bone marrow is greater than 20% of all nucleated (nucleus-containing) cells. The M4E variant also contains a number of abnormal eosinophils (granular leukocyte with a two-lobed nucleus) in the bone marrow.
monocytic leukemia (M5) - There are two forms of this subtype. The first form is characterized by poorly differentiated monoblasts (immature monocytes) with lacy-appearing genetic material. The second, differentiated form is characterized by a large population of monoblasts, promonocytes, and monocytes. The proportion of monocytes in the bloodstream may be higher than that in the bone marrow. M5 leukemia may infiltrate the skin and gums, and it has a worse prognosis than other subtypes.
erythroleukemia (M6) - This form of leukemia is characterized by abnormal red blood cell-forming cells, which make up over half of the nucleated cells in the bone marrow.
megakaryoblastic leukemia (M7) - The blast cells in this form of leukemia look like immature megakaryocytes (giant cells of the bone marrow) or lymphoblasts (lymphocyte-forming cells). M7 leukemia may be distinguished by extensive fibrous tissue deposits (fibrosis) in the bone marrow.
In addition, patients sometimes develop isolated tumors of the myeloblasts (early granulocytes). An example of this is isolated granulocytic sarcoma, or chloroma - a malignant tumor of the connective tissue. Individuals with chloroma frequently develop AML, so they usually are treated with an aggressive, AML-specific chemotherapy program.

Chronic Myelogenous Leukemia (CML) Chronic myelogenous leukemia (CML) is known as a myeloproliferative disorder - that is, it is a disease in which bone marrow cells proliferate (multiply) outside of the bone marrow tissue.
CML is easy to diagnose, since it has a genetic peculiarity, or marker, that is readily identifiable under a microscope. About 95% of CML patients have a genetic translocation between chromosomes 9 and 22 in their leukemic cells. This abnormality, which is known as the Philadelphia chromosome (Ph1), is named after the city in which it was discovered. The Philadelphia chromosome causes uncontrolled reproduction and proliferation of all types of white blood cells and platelets (blood clotting factors). Sadly, CML is not yet curable by standard methods of chemotherapy or immunotherapy.
CML tends to occur in middle- and retirement-aged people (the median age is 67 years). It occasionally affects people in their 20s, but it is rare in the very young; only 2% to 3% of childhood leukemias are CML. Early disease often is without symptoms (asymptomatic) and is discovered accidentally. Individuals with more advanced cases of CML may appear sickly and experience fevers, easy bruising, and bone pain. Laboratory and physical findings include enlarged spleen (splenomegaly), a high white blood cell count, and absent or low amounts of the white blood cell enzyme alkaline phosphatase.
Like other forms of leukemia, CML is not "staged". Rather, this unstable disease is categorized according to the three phases of its development: chronic, accelerated, and blast.
Chronic phase - Patients in this initial phase have fewer than 5% blast cells and promyelocytes (immature granulocytes) in their blood and bone marrow. This phase is marked by increasing overproduction of granulocytes. Individuals generally experience only mild symptoms, and they respond well to conventional treatment.
Accelerated phase - Patients in this progressive phase have more than 5%, but fewer than 30% blast cells. Their leukemic cells exhibit more chromosomal abnormalities besides the Philadelphia chromosome, and so more abnormal cells are produced. Noticeable symptoms such as fever, poor appetite, weight loss occur, and patients may not respond as well to therapy.
Blast phase (acute phase, blast crisis) - Patients in this final phase have more than 30% blast cells in their blood and bone marrow samples. The blast cells frequently invade other tissues and organs outside of the bone marrow. During this phase, the disease transforms into an aggressive, acute leukemia (70% acute myelogenous leukemia, 30% acute lymphocytic leukemia). If untreated, CML is fatal in roughly 20% of all patients each year.
Acute Lymphocytic Leukemia (ALL) Acute lymphocytic leukemia (ALL) - also known as acute lymphoblastic leukemia - is a malignant disease caused by the abnormal growth and development of early nongranular white blood cells, or lymphocytes. The leukemia originates in the blast cells of the bone marrow (B-cells), thymus (T-cells), and lymph nodes. ALL occurs predominantly in children, peaking at 4 years of age. ALL is seen more frequently in industrialized nations, and it is slightly more common among white children and boys.
ALL often is diagnosed after a patient experiences a 4- to 6-week period of illness. Initial symptoms may include a nonspecific infection (e.g., respiratory infection) that persists or recurs despite antibiotic therapy. During this period, the person may start to experience aching bone pain in the back, limbs, and/or joints. Walking difficulties may be seen in some children who have extreme swelling of the large joints. But the symptoms that most often suggest referral for a blood count (measure of the number of blood cells within the blood) are a purplish-brown rash or the onset of excessive bruising.
If ALL is T-cell in type, the thymus is involved. Leukemia-related enlargement of the thymus may lead to coughing, shortness of breath, or compression of the superior vena cava (SVC), the large vein that carries blood from the head and arms back to the heart). Such venous blockage may induce head and arm swelling and may cause a life-threatening condition known as SVC syndrome.
Both children and adults with ALL are at risk of developing complications due to central nervous system (CNS) involvement. CNS invasion is especially likely among patients with the L3 subtype of ALL. When leukemic cells infiltrate the CNS, they can cause increased pressure within the skull and paralysis of cranial nerves that connect the brain with other organs, muscles, etc.
Age is an important prognostic factor in ALL. Studies have suggested that patients who are younger than 35 years of age fare better than older patients; however, this observation may be related to the higher incidence of the Philadelphia chromosome (Ph1) among older ALL patients - a subgroup that has a poorer chance of survival. Fortunately, though, 60% to 80% of children and adults with ALL will achieve complete remission of the disease after completing appropriate therapy.
There is no standard staging system for ALL. Rather, ALL is categorized according to a system known as the French-American-British (FAB) Morphological Classification Scheme for ALL:
L1 - Mature-appearing lymphoblasts (T-cells or pre-B-cells). Cells are small with uniform genetic material, regular nuclear shape, nonvisible nucleoli (round bodies within the nucleus, the site of RNA synthesis), and little cytoplasm (substance of a cell, excluding the nucleus).
L2 - Immature and pleomorphic (variously shaped) lymphoblasts (T-cells or pre-B-cells). Cells are large and variable in size, with variable genetic material, irregular nuclear shape, one or more large nucleoli, and variable cytoplasm.
L3 - Lymphoblasts (B-cells; Burkitt's cells) are large and uniform; genetic material is finely stippled and uniform; nuclear shape is regular (oval to round); there are one or more prominent nucleoli; and cytoplasm is moderately abundant.
Chronic Lymphocytic Leukemia (CLL) Chronic lymphocytic leukemia is the most common leukemia in North America and in Europe. It is a disease of older adults and is very rare among people who are younger than 50 years of age. Men with CLL outnumber women by a 2-to-1 average. The disease usually is detected accidentally during a doctor's examination for an unrelated complaint.
CLL is thought to result from the gradual accumulation of mature, long-lived lymphocytes. Therefore, this cancer is caused not so much by overgrowth as it is by the extreme longevity and build-up of malignant cells. Although the rate of accumulation varies among individuals, the extensive tumor burden eventually causes complications in all CLL patients.
CLL is classified by one of two staging systems, although these systems are based on cytology (the study of cell characteristics) and are different from the staging used to evaluate other, nonleukemic cancers. The first system - known as Rai Classification - is used more often in the United States; the other system - known as Binet Staging - is more popular in Europe. Both methods are correlated with prognosis.

The process of becoming a Bone Marrow Donor is very simple through the Anthony Nolan Trust
1) You need to make sure you meet the following General Criteria:
- age 18 - 40 : health and circumstances permitting, you remain on the Register until your 60th birthday, so don't be put off joining if you are close to 40
- in general good health
- weight over 51kg / 8 stone
- women must not be pregnant
- women with children under the age of 12 months cannot join the register or donate marrow during that time
In addition you will need to check that you not excluded through the Medical Criteria (set out below)
Although it costs up to £70 to recruit each donor, tissue-type each sample, and maintain the donor's records there is no cost or charge for you and you can ‘sign up’ from anywhere in United Kingdom, so long as you are a UK resident.
2) Completing the Paperwork
You can obtain an information pack and medical questionnaire in four ways:
- calling Anthony Nolan hotline number - 0901 88 22 234 : calls are charged at 25p per minute and a proportion of the call charge comes to the Trust
- writing to: The Anthony Nolan Trust, Units 2 - 3, Heathgate Place, 75 - 87 Agincourt Road, London, NW3 2NU
- attending a donor recruitment clinic near you
- email: newdonor@anthonynolan.org.uk
3) Giving a Blood Sample
A blood testing kit can be sent to you by the Anthony Nolan Trust, so that you can take this to your local GP or health clinic, where a small sample of your blood will be taken - about 4ml. Needless to say, on no account should you attempt to take the sample yourself.
The sample will be forwarded to the Anthony Nolan laboratories, where it is tested to establish your tissue type. The results are stored on their database, which is, of course, confidential.
As a new member of the Register you will receive confirmation of your status as a potential life saver.
You may be found to be a match for a patient almost immediately; other people wait many years before being asked to donate - and some never are.
Every single person on our Register is still making a wonderful commitment – to make themselves available to support another person in need of a life saving transplant.

Find out more at www.anthonynolan.com

Medical Criteria
For a variety of reasons which can relate to the outcome of a transplant, or to your own welfare as a donor, certain conditions prevent you from joining the Register.
The application you complete before giving a blood sample covers all of the following medical conditions.

ALCOHOL
Sometimes Acceptable
No - if you are alcoholic or regularly consumer more than 40 units a week as a man or 30 units a week as a woman; or if you are on antabuse.
Exception - if you have recovered from alcoholism, and it has been two years or longer since recovery

ALLERGY : drug-induced
Generally Not Acceptable
Exception - if environmentally produced

ANAEMIA
Generally Acceptable
No - especially if there is a history of persistent anaemia or if someone is regularly anaemic i.e. more than three times a year.
Exception - you are only temporarily or rarely anaemic, you are not taking medication and you haemoglobin count is within the accepted range

ANKYLOSING SPONDYLITIS
Definitely not acceptable

ANGINA
Definitely not acceptable

ASTHMA
Generally not acceptable
No - if you are on continuous high dose medication (more than 8 inhalations /puffs per day) as people suffering from asthma are more likely to have post-operative complications.
Exception - if medication is taken rarely, less than 8 inhalations/puffs per day or if the asthma is brought on by an allergy

BACK PROBLEMS
Generally Not Acceptable
No - if upper back / neck problems, chronic lumbar vertebrae problems, such as slipped discs or sciatica, chronic lower back problems, or any injury which means that you are have to avoid certain sports, heavy lifting, prolonged seating
Exception - minor muscular problems or minor problems in the cervical or thoracic areas of the spine

BRAIN SURGERY
Generally Not Acceptable
Exception - if the brain surgery was performed after September 1992

CANCER
Definitely Not Acceptable
No - if any form of cancer including skin cancer even if you have been given the all clear by your treating physician.

CHRISTMAS DISEASE
Definitely Not Acceptable

CIRRHOSIS
Definitely Not Acceptable
No - there is a risk with general anaesthetic and bleeding.

COAGULATION DISORDERS
Definitely Not Acceptable
No - if you have a history of DVT, PE, Leiden factor, Von Willebrands.

CELIAC DISEASE
Definitely Not Acceptable
No - intolerance to gluten may relate to the auto-immune system

CROHN'S DISEASE
Definitely Not Acceptable
No - auto-immune

CYSTIC FIBROSIS
Definitely Not Acceptable
No - medical risks associated with general anaesthetic

DEPRESSION
Generally Acceptable
No - if endogenous, manic or severe.
Acceptance criteria - mild, short-term reactive depression with short term medication
N.B. individual assessment is obligatory

DIABETES
Generally Not Acceptable
No - insulin or tablet dependent diabetes can be associated with auto-immune disease which could be passed on to the patient.
Exception - non insulin-dependent diabetes, well controlled by diet

DERMATITIS HERPETIFORMIS
Definitely Not Acceptable
No - as often associated with coeliac disease.

DOWNS SYNDROME
Definitely Not Acceptable

ECZEMA
Generally Acceptable
No - if atopic (since childhood and severe) or if auto-immune related
Exception - mild and irregular

ENDOMETRIOSIS
Generally Acceptable
Acceptance Criteria - if well controlled.

EPILEPSY
Generally Not Acceptable
No - if on medication, due to risks associated with general anaesthetic
Exception - if you have not had a seizure for a minimum of 3 years and have not taken medication during that time. Donors must be aware that there is a small risk of fitting when awakening from the anaesthetic but this can be well-controlled

GALL STONES
Generally Not Acceptable
Exception - If you have undergone surgery and have no current problems.

GASTRO-INTESTINAL SYMPTOMS such as ulcers, general gastritis
Generally Acceptable
Exception - If the condition is well-controlled, with no internal bleeding or other complications.

GLANDULAR FEVER
Generally Acceptable
No - if a current condition or if you are still suffering from after effects
Acceptance criteria - if in the past and mild.

GRAVES DISEASE
Definitely Not Acceptable
No - auto-immune

HEART CONDITIONS
Generally Not Acceptable
No - angina, cardiomegeneral anaestheticity, cardiomyopathy, past history of heart attacks, heart arrhythmia, pacemaker, or a congenital condition such as thickened valve, hole in heart, heart murmur or any other condition which requires individuals to take antibiotic cover at any time, as all are considered a risk under general anaesthesia
Exception - if you have a congenital heart condition but do not have to take any prophylactic antibiotic cover at any time and are in good health

HEPATITIS A
Generally Acceptable
Acceptance criteria - if you have been clear for longer than 12 months and you are currently asymptomatic.

HEPATITIS B OR C
Definitely Not Acceptable
No - these viruses are found in body fluids, including blood and bone marrow.

HIGH BLOOD PRESSURE
Generally Not Acceptable
Exception - if the condition is well-controlled by medication and the most recent blood pressure reading is below: 150/95

HIP REPLACEMENT
Generally Acceptable
Acceptance Criteria - as long as no current problems at all but you must be aware that some short-term back pain could arise if you donate

HIV EXPOSURE
Definitely Not Acceptable
No - if you have been knowingly exposed to HIV you are considered a high risk category

HUMAN PITUITARY EXTRACT TREATMENT
Generally Not Acceptable
No - if treated with growth hormones or gonadotrophins
Exception - if treatment started after 1987

HYPOTHYROIDISM (MYXOEDEMA)
Generally Not Acceptable
Exception - if the cause is not auto-immune related

HYSTERECTOMY
Generally Acceptable
Acceptance Criteria - if the operation was over 6 months ago and there were no malignancies

ITP
Definately Not Acceptable
No - auto-immune

JAUNDICE
Generally Not Acceptable
Exception - the jaundiced was experienced as a baby or at a young age.

LUPUS (SLE)
Definitely Not Acceptable
No - auto-immune

MAJOR SURGERY OR OPERATION
Generally Not Acceptable
Exception - if at least six months must have elapsed since the operation and you are clear of all post operative symptoms.

MALARIA
Generally Not Acceptable
No - especially if within the last 12 months
Exception - if you have taken a full course of anti-malarial tablets, the timespan was longer than 12 months ago, and no symptoms are being experienced

ME / POST VIRAL SYNDROME
Generally Acceptable
Acceptance Criteria - only one episode over 12 months ago and no relapses have occurred

MIGRAINE
Generally Acceptable
Acceptance Criteria - if mild or infrequent (less than every 2 months

MS
Definitely Not Acceptable
No - auto-immune

MYASTHENIA GRAVIS
Not Acceptable
No - Autoimmune

OCD (OBSESSIVE COMPULSIVE DISORDER)
Generally Not Acceptable
No - especially if severe
Exception - depends on severity/ treatment - individual assessment necessary

OSTEO-ARTHRITIS
Generally Acceptable
No - especially if severe
Acceptance Criteria - if the treatment is mild, you are not on steroids and the hip and spine areas are unaffected

OSTEOGENESIS IMPERFECTA
Definitely Not Acceptable
No - there is a risk of fracture

OSTEOPOROSIS
Definitely Not Acceptable
No - a risk of bone damage

PANCREATITIS
Generally Not Acceptable
No - especially if chronic and with diarrhoea.
Exception - if there has been just one episode and you are fully recovered

PARAPLEGIC / TETRAPLEGIC
Not Acceptable

PERICARDITIS
Generally Not Acceptable
Exception - if fully recovered and no antibiotic cover needed

PERNICIOUS ANAEMIA
Definitely Not Acceptable
No - auto-immune

PITUITARY TUMOUR
Generally Not Acceptable
Exception - if benign, with no post-operative complications

PLEURISY
Generally Not Acceptable
Exception - if just a single incident with no recurrence

POLIO
Generally Not Acceptable
No - with serious physical disabilities which could be aggravated by donating marrow
Exception - if mild and no serious physical disabilities

POLYCYSTIC KIDNEY
Not Acceptable

PRE-CANCEROUS CELLS
Generally Not Acceptable
Exception - if your last two smear tests have been clear

PREGNANCY
Generally Not Acceptable
Exception - you can only join after your baby is 12 months old

PROCTITIS
Generally Not Acceptable
No - If autoimmune

PSORIASIS
Generally Not Acceptable
Exception - if very mild

PSORIATIC ARTHRITIS
Definitely Not Acceptable
No - auto-immune

PULMONARY EMBOLISM
Definitely Not Acceptable

PUPURA
Definitely Not Acceptable
No - could be auto-immune

RAYNAUD'S SYNDROME
Generally Not Acceptable
No - if associated with SLE

ROSACEA
Generally Not Acceptable
Exception - if localised, e.g. on the face.

RHEUMATIC FEVER
Definitely Not Acceptable

RHEUMATOID ARTHRITIS
Definitely Not Acceptable
No - auto-immune disease

SARCOIDOSIS
Definitely Not Acceptable
No - the cause is unknown, can affect any system, heart, lungs bone

SCIATICA
Generally Not Acceptable
Exception - the condition is mild and does not interfere with your normal lifestyle

SCHEUERMANNS DISEASE
Generally Not Acceptable
Exception - no current problems

SCHIZOPHRENIA
Definitely Not Acceptable
No - medication given is usually a contra-indication to general anaesthetic

SCOLIOSIS
Generally Not Acceptable
Exception - if you have no current back problems or rods inserted

SICKLE CELL DISEASE
Generally Not Acceptable
Exception - as trait only

SLEEP APNOEA
Definitely Not Acceptable
No - there is a risk with airway post general anaesthetic

SLE
See Lupus

SPINA BIFIDA OCCULTA
Generally Not Acceptable
Exception - if you are free from problems or mobility problems

TACHYCARDIA
Generally Not Acceptable
Exception - if mild and you are not on medication

TATTOOS / BODY PIERCING (Recent)
Generally Not Acceptable
Exception - if 12 months since tattoo or piercing

TAY SACHS DISEASE
Generally Not Acceptable
Exception - as trait only

TESTOSTERONE INJECTIONS
Generally Not Acceptable
Exception - synthetic injection

THALASSAEMIA
Generally Not Acceptable
Exception - as trait only

THROMBOCYTOPENIA
Definitely Not Acceptable

THYROID
Generally Acceptable
No - if you have Graves disease or Hashimoto's disease, due to auto-immune association
Acceptance Criteria - if you are on thyroxine. If you are on other drugs individual assessment is necessary

TB
Generally Not Acceptable
Exception - if you have been clear for more than 24 months and are not on medication

TURNERS SYNDROME
Generally Not Acceptable
Exception - if the donor has no heart problems

ULCERATIVE COLITIS
Definitely Not Acceptable
No - auto-immune.

URTICARIA
Generally Not Acceptable
Exception - if the condition is mild. Individual assessment is necessary

VITILIGO
Definitely Not Acceptable
No - can be associated with auto-immune disorders.

The following medical conditions do not preclude donating, but should be noted on your registration to join our bone marrow register :
- Gilberts' syndrome
- Hormone replacement therapy
- Irritable bowel syndrome
- PID (Pelvic Inflammatory Disease)
- peritonitis
- polycystic ovary
- renal colic (kidney stone)
- shingles
- termination of pregnancy
- Toxoplasmosis

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.