k

.

:1,

‘2

:: Bone Marrow Transplantation: T Clinical and Aspects1 Shayle Claire Robert Herbert

Radiologic

B. Patzik, MD Smith, MD A. Kubicka, MD Kaizer, MD, PhD

With

the

advent

ofhistocompatibility

typing,

use

ofbone

marrow

transplantation increased. .

.

I

for treating hematogenous cancer has dramatically Marrow grafting is preceded by intense immunosuppressive, marrow ablative treatment, usually with high-dose chemotherapy and whole-body irradiation. Because the recipient may be immunocompromised for months after transplantation due to this regimen, complications are numerous. Complications are classified according to the following intervals: pre-engraftment (from pretransplantation treatment to engraftment), postengraftment (3 months afterward), and delayed (longer than 3 months after engraftment) Pre-engraft.

ment

complications

include

bacterial,

fungal,

and

viral

infections;

tis-

sue-damaging effects (eg, toxic pneumonitis) ; hepatic veno-occiusive disease; and graft rejection. Postengraftment complications include viral, fungal, and protozoa! infections; acute graft-versus-host disease (GVHD); and pneumatosis intestinalis. Delayed complications include chronic GVHD and recurrence of cancer. As part of the follow-up team, radiologists should be familiar with clinical aspects of marrow transplantation and be alert for early, potential life-threatening cornplications. U INTRODUCTION Great strides have been made in the use of bone peutic technique. In the past decade, the number plantations performed worldwide has increased

Abbreviations: Index

GVHD

terms:

Bone

RadloGraphics ‘

From

plant 1990 May C

1991;

the

Department

Center (H.K.), RSNA scientific 3. Address

RSNA,

reprint

graft-versus-host

marrow,

disease,

transplantation,

441

HLA

1.455

=

human

#{149} Grafts,

marrow transplantation and variety ofbone (1).

lymphocyte infection

as a theramarrow

trans-

antigen #{149} Leukemia,

myelogenous,

40.341

11:601-610 of Diagnostic

Radiology

Rush-Presbyterian-st

assembly. requests

Luke’s

Receivedjanuary

and

Nuclear

Medicine

(S.B.P.,

CS.,

R.A.K.)

and

the

Bone

Marrow

Trans-

Medical Center, 1653 W Congress Pkwy, Chicago, IL 60612. From the 16, 1991; revision requested March 14 and received April 20; accepted

to S.B.P.

1991

601

Figure

1.

marrow

bone

Bone

defects

aspiration.

marrow

after

Radiograph

donor

shows

bone of a multi-

pie, small, round areas of decreased opacity in the iliac crests that coincide with the sites of marrow aspiration. Sclerosis around these areas indicates healing. These areas can cause considerable confusion to radiologists if the pertinent past medical history is not available.

Bone marrow transplantation whole organ transplantation. pluripotent

stem

cells

are

differs from In the former, transferred

This

from

tion

donor to recipient; those cells must regenerate the entire marrow system of the host. Improvements in histocompatibiity typing and supportive

the

care

long-term

have

increased

survival

the

of bone

chances

marrow

of

recipi.

myelogenous

leukemia

who

emphasizes

and

cure.

Commonly,

intensity

plantation,

referring

continued tial

for

tial

of these

recipients

return home to their primary physicians for follow-up and radiologic monitoring. It is essenradiologists

to be

familiar

portant clinical aspects of bone plantation and the complications develop in these patients. The be the first physician to detect life-threatening

abnormality.

with

the

im-

marrow trans. that may radiologist may an

early,

poten-

diation

. The and neic,

for

Sources

it possible

U

Patzik

et a!

limits

the

therapy

marrow system large

or total

is

transis regendoses

body

irra-

cure.

of Marrow between the marrow donor can be syngeneic, alloge-

autologous

allows

in patients

RadioGrapbics

that

to use

agents

relationship the recipient or

factor

the

(3)

donor

.

and

In syngeneic

trans-

recipient

are

identi-

cal twins (ie, have identical genomes). In allogeneic transplantation, the donor of the bone marrow is genetically different from the recipient, although they are usually HLA matched. When all HLAs are matched, a decrease in frequency and intensity of graft-versus-host disease (GVHD) is observed (4). In autologous transplantation, the patient’s own bone marrow is aspirated, subjected to dure

U

that

BONE

cytoreductive

With bone hematopoietic

cryopreservation,

602

evaluation

complications

the

of systemic

in a tertiary

transplant

practical

unique

ASPECTS OF TRANSPLANTATION

myelosuppression. plantation, the erated, making of chemotherapeutic

many

basic transplanta-

develop.

lymphocyte antigen (HLA)-matched Its role is expanding in the treatment acute leukemias, Hodgkin and nonHodgkin lymphoma, aplastic anemias, and congenital immunodeficiency disorders. Bone marrow transplantation is also being investigated for use in patients with selected solid tumors (2). Although the bulk of the initial radiologic workup for these patients may be performed center,

important

marrow the

multiple

U CLINICAL MARROW

ble have

human donors. of the

medical

the

of bone

Many malignant diseases are not curable by means of surgery or other regional therapy. In these patients, systemic chemotherapy offers the only chance for disease control and possi-

The great majority of bone marrow transplantations are performed in patients with cancer. Currently, bone marrow transplantation is the treatment of choice for patients chronic

and

may

reviews

aspects

of the

ents.

with

article

clinical

and

more with

reinfused.

intensive disseminated

Volume

This

systemic

proce-

therapy

disease.

11

Number

4

.

Patient

crease

Preparation

preceded by intense, immunosuppressive, marrow ablative treatment of the recipient. This conditioning treatment commonly consists of high-dose chemotherapy, frequently combined with to. tal body irradiation. Goals in preparing the patient for transplantation include destruction of neoplastic cells; destruction of endogenous hematopoietic cells to provide space for the infused marrow; and, in the case of the allogeneic transplant, immunosuppression to prevent graft rejection in the recipient (5). Marrow

.

grafting

Bone

and

is almost

Marrow

always

Acquisition

Infusion

The aspiration and infusion of bone marrow are relatively simple procedures that do not involve surgery and are rarely associated with serious morbidity (6). Marrow aspiration is performed

in the

operating

room

with

of either general or spinal anesthesics. most common site from which bone is acquired

is the

posterior

ilium

(Fig

the

use

The marrow 1).

sufficient

to achieve

engraftment

average adult patient. The particles from the aspirate are strained through multiple stainless steel filters to produce a suspension of single cells (7) . The suspension is preserved in tissue culture medium containing heparin and is either frozen and stored or infused intravenously into the recipient. In autologous transplantation, the marrow is frozen before reinfusion.

Support

In contrast

to the

acquisition

and

relative infusion

tensive pretransplantation men predisposes the bidity

and

death

simplicity procedures,

cytoreductive patient to serious

following

of marrow the

in-

regimor-

1991

red

transfublood

cells,

prophylactic antibiotics. The most common early signs of engraftment are rise in total leukocyte count, foltowed by a rise in granulocytes. Platelets are usually the last to recover. As expected, the regenerating bone marrow is the donor’s genetic type (5).

U

PRE-ENGRAFTMENT

COMPLICATIONS Complications after bone marrow transplantation are numerous. Because recipients of bone marrow transplants may be immunocompromised for months after engraftment as a consequence of chemotherapy, radiation therapy, or GVHD, complications can be seen at any time after transplantation. Radiologically, complications can be grouped according to the approximate interval when they are most likely to occur: pre-engraftment, postenand

delayed.

The period

pre-engraftment or peritransplantation begins when the immunosuppressive marrow ablative treatment is begun and extends until bone marrow engraftment. Complications are mostly infections but can also include the tissue-damaging effects of the systemic cytoreductive therapy, veno-occlusive disease of the liver, and graft rejection.

.

Infections

After the patient temic chemotherapy the bone marrow This

can

graftment

last

for

undergoes substantial sysand radiation treatment, is left in an aplastic state. 4 weeks

occurs

hematopoietic other neutropenic ents are highly

and

or more, an

until

adequate

en-

number

of

cells

are produced. As with patients, transplant recipisusceptible to infections. It is

uncommon

for

a patient

to remain

afebrile throughout the entire posttransplantation course. Clinical or microbiologic evidence of infection is present in about 30% of these patients. Most documented infections are caused by bacteria or fungi (8).

transplantation.

After the bone marrow transplantation, the patient needs to be supported until the transplanted progenitor cells begin producing blood cells. The time interval in which the progenitor cells produce an adequate amount of blood elements to sustain the patient ranges between 3 and 10 weeks. Mandatory supportive therapies include isolation to de-

July

packed

and

extremely

Patient

of infection, and

in

the

.

occurrence

of platelets

graftment,

Re-

peated aspirations may be needed to obtain the necessary amount of bone marrow. Only approximately 2% of the donor’s bone marrow cells are aspirated. Because only a relatively small number of progenitor cells are required to support regeneration of the entire lymphohematopoietic system, this volume is usually

the

sions

Bacterial Infections-The bacterial organism causing tures in marrow transplant phylococcus epidermidis usually the central venous

Patzik

most common positive blood culrecipients is Sta(8). The source is catheters used in

Ct

a!

U

RadioGraphics

U

603

Figure 2. Acute plete opacification

sinusitis. of both

Radiograph shows commaxillary sinuses, con-

sistent

sinusitis.

This

with

acute

is a common

source ofsepsis in neutropenic the peritranspiantation period.

Figure

3.

Esophago-

gram

gross

shows

sloughing,

with

membranes

mucosal pseudo-

of necrotic

throughout

agus.

the

Although

tis-

esoph-

candidiasis

may be suspected, endoscopy is usually necessary to confirm diagnosis.

Figure

4.

tomographic attenuation necrosis.

all such bacterial

patients. organisms

Other commonly isolated include Escbericbia coli,

Klebsiellapneumoniae,

and

inosa, ganisms

Pseudomonas

Staphylococcus

commonly

aureus.

cause

out an identifiable source. the paranasal sinuses may occult infection (Fig 2).

a bacteremia

Disseminated

asis

and

species candidal

(8).

604

U

RadioGraphics

U

Patzik

(Fig

et a!

occur

as-

orwith-

common by Candida and

can

A necrotic

aerug-

These

more

esophagitis

frequently. Aspergillosis locally (Figs 4-6).

Computed

upper lung was seen at radiography. pergilloma was found at bronchoscopy.

In our experience, often harbor an

Mucocutaneous

aspergillosis.

(CT) scan shows a central area of low with an air-fluid level compatible with An ill-defined soft-tissue mass in the right

Virallnfections.-The

most

infections in the caused by herpes gingivostomatitis,

Fungal Infections.-The gal infections are caused pergillus

during

Candidal

esophagitis.

sue

patients

funAs-

can with

occur.

frequent

pre-engraftment simplex virus esophagitis,

These

acyclovir

infections

or

may

viral

period are (8) . Severe pneumonitis

be controlled

therapy.

candidi-

.

3) occur

diffusely

or

Tissue-damaging

Pretransplantation cause severe toxic branes, gastrointestinal der, central nervous

Effects conditioning regimens can effects in the mucous memtract, liver, lung, bladsystem, and other tissues

Volume

11

Number

4

Figures

5, 6.

(5)

right

Aspergillosis

mass

in the

upper

(b)

T2-weighted

magnetic

the

right

lobe

parietal

(6) Pulmonary

of the

lung

that

cavity

position.

(b)

“fungus

ball”

CT

resonance

brain.

image

an

right

better

ofAspergillus

upper

shows

lobe. the

brain

The

lesion.

anemia

or

Within apy,

2 weeks

patients

involving

often the

esophagitis. most

weeks. regimen

July

Diarrhea must

1991

have

since

conditioning malignant

mass

shows

shows

patient

a focal died

radiograph moved

At pathologic

they

treatment disease.

of pretransplantation develop

oropharynx, Nausea

patients

radiograph The

area

shows the

signal

aspergillosis

a soft-tissue patient

examination,

the

round

mental

of increased

of disseminated

when

a large,

developed

mass

was

turned

ovoid

mass

soft-tissue confusion.

intensity

in

4 days

later.

(arrow) with a to the decubitus proved

to

be

a

hyphae.

immunodeficiency,

require less intensive than do patients with

Chest

patient

chest The

(9). As expected, complications due to toxicity are generally less severe in patients who undergo bone marrow transplantation for aplastic

(a)

aspergilloma.

of the

location.

(a) Posteroanterior

in the

scan

and

to be

in a parasagittal

aspergilloma.

well-defined

lung

proved

and

mucositis or without

vomiting

moderate

related to the be distinguished

dition

ther-

severe with

occur, diarrhea

and for

otic-induced pseudomembranous colitis, viral or bacterial gastroenteritis, or diarrhea due to GVHD (9). Toxic pneumonitis related to the pretransplantation regimen may also occur. This con-

2-4

may

be

difficult

pneumonitis due to infections. There is for idiopathic toxic some patients have oids (9).

to distinguish

from

cytomegalovirus or other no established treatment pneumonitis, although responded to corticoster-

conditioning from antibi-

Patzik

et a!

U

RadioGraphics

U

605

8.

7. Figures

7, 8.

(7) Viral

4 weeks

before

shows

Cultures graph finding

pneumonitis. diffuse bilateral

of bronchoscopic shows severe in P carinil

other

include

were

interstitial

pneumonia.

Miscellaneous effects

aspirate

diffuse

Chest radiograph of a patient who received a bone marrow transplant interstitial infiltrates, more pronounced in the middle of the left lung.

positive

infiltrates

Bronchoscopic

tissue-damaging

hemorrhagic

cystitis

due

cultures

Hepatic

Veno-occiusive

Graft

.

to

Graft

or

pneumonia. a pneumothorax,

and

Chest a common

radio-

Rejection

rejection is an uncommon complication following transplantation for malignant disease. Occasionally, after transplantation, the bone

marrow

sequently specimens void

Disease

(8) P carinii

both lungs grew P carinii.

side

cyclophosphamide therapy, central nervous system complications with severe dementia leukoencephalopathy, sterility for men and women, and cataracts (9).

.

for cytomegalovirus. throughout

may

stops from

ofmyeloid

begin

to function

producing such cases, elements.

but

sub-

cells. In biopsy the marrow is deGraft

rejection

oc-

veno-occiusive disease, clinically by abdominal pain, hepatomegaly, ascites, and jaundice, develops in over 20% of recipients of bone marrow transplants (10). The condition is defined as a

curs most frequently in patients who have undergone transplantation for aplastic anemia. The cause of marrow rejection is uncertam, but it may be related to sensitization of the recipient due to prior blood transfusions

nonthrombotic

(3).

Hepatic

characterized

occlusion

veins produced thelium. The by the

of small

by inflammation disease is thought

chemotherapeutic

agents

therapy used before tation. Duplex Doppler in detection

bone

and

marrow

sonography

of hepatic

intrahepatic

of the endoto be caused

veno-occlusive

radiation

transplanmay

be useful disease,

even in its early or subclinical stages, if serial studies are obtained and compared with baseline images before chemotherapy and transplantation (11).

U

POSTENGRAFTMENT

COMPLICATIONS The postengraftment period lasts for 3 months after engraftment. Postengraftment complications include infections; acute GVHD, which is the most common complication

during

this

period;

and

pneumatosis

in-

testinalis.

.

Infections

infections of the pre-engraftment the majority of infections that after the period of initial engraftment to opportunistic organisms, particularly Unlike

phase,

ruses,

606

U

RadioGrapbic.s

U

Patzik

et a!

fungi,

and

occur are due vi-

protozoa.

Volume

11

Number

4

igure

9.

skin

L

Severe

acute

in an infant

ved a bone

GVHD

who

of

recently

marrow

transplant.

F--e is a diffuse macular, erytheriatous rash involving most of the LAW,, with areas of skin desquama-

The

Virallnfections.tions

to occur

period are varicella-zoster

during

viral,

infectious

that

monia,

adenovirus

a diffuse

especially About

pneumonia

50% seen

mately

15%

positive

for

of the

mortality pneumonia

acute immune

the

or

because

to treat

Fungal

Infections.-Both

with

op.

and

period

tends viral

to occur esophagitis

and

between sity

by the

GVHD

it-

immunosuppressive

or prevent

it (13).

candidal

after may

occur

during

this

esophagitis

transplantation exhibit

some

than un-

features, candidiasis may be clinically and radiologically indistinguishable from infections caused by other agents. Endoscopic examination of the esophagus is often necesfor

definite

1991

during

regimen,

tity

bone

of the who

and

of the

ditioning

recipient, the

marrow

the

inten-

con-

nature

and

transplant

of acute

GVHD

receive

allogeneic

fre-

of GVHD disparity

pretransplantation

and

siblings

The

manifestations degree ofgenetic

quan-

itself.

is 30%-60% transplants

The

in pafrom

(2).

The skin, liver, and gastrointestinal tract are the targets of acute GVHD. Acute GVHD of the skin causes a macular erythematous rash on the face, trunk, and extremities (Fig 9). Acute GVHD also causes elevation in the 1evels of hepatic enzymes and may lead to liver

diagnosis.

Protozoal Infections. flu commonly caused transplant recipients

July

donor

toxicity

HLA-identical

infec-

complica-

recipients

by T lymphocytes.

clinical by the

the

and

frequency

usual

sary

a rare

transplantation.

common

transplant

is mediated

reducing

either

candidal

later

is currently marrow

is a relatively

in allogeneic

quency and are affected

with

by

can

Although

sulfamethoxcomplication,

GVHD

GVHD

patient’s

infection

aspergillosis

(8).

and this

the first 3 months after engraftment (4). Acute GVHD results from engraftment of immunocompetent cells from the donor bone marrow that react against recipient tissues. The reac-

tients tions

of bone

Acute

tion

of cytomegaloviin patients

of the

used

tests

a 50%-60%

the

. tion

a severe

even

reduces

competence

therapy

blood

with

frequency

to control

pneumonia

P caninli

Acute

develop which,

GVHD

of intersti-

whose

is higher

GVHD.

ability

The

infecpneu-

cases

is associated

(3).

for

Toxoplasma gondii infection occurs rarely. When it does, it is usually due to reactivation of latent organisms and commonly involves the brain, heart, and lungs (8).

herpes

agent, most com(Fig 7) (12). Approxi-

pneumonitis, treatment,

effective

complication

transplantation

patients

trimethoprim

is highly

of allogeneic

cytomegalovirus

interstitial timal

ofall

and

and common

interstitial

after

prophylactic azole

and

in recipients

have a definable etiologic monly cytomegalovirus

self

infec-

cytomegalovirus being the most

and

produce

transplants.

rus

common

postengraftment

virus being less common (8). lungs are often the site for viral

tions

tial

with virus

agents

simplex The

most

the

-Pneumocystis canpneumonia in marrow in the past (Fig 8). Use of

Patzik

et a!

U

RadioGrapbic.s

U

607

10. Figures 10, 11. diced approximately study demonstrates a ribbonlike

11. Acute GVHD in a patient who experienced episodes ofdiarrhea and became jaun1 month after bone marrow transplantation. Image from a small bowel follow-through classic changes of GVHD. The mucosa is sloughed, causing a loss of mucosal contour

(10)

appearance

to the

bowel.

It may

be difficult

to differentiate

acute

GVHD

of the

bowel

from

and viral

gastroenteritis, radiation effects, or ischemia on the basis of radiologic findings alone. Usually, the clinical circumstances are not confusing. (11) Acute GVHD in a patient who underwent bone marrow transplantation 6 weeks before. In the previous 3 weeks, she developed nausea, vomiting, and diarrhea and began to have clay-colored stools. Image from an upper gastrointestinal tract series shows a diffuse abnormality in the small bowel. There are thickened folds, separation ofbowel loops, and patchy areas ofmucosal destruction. The transit time was remarkably rapid; contrast material was seen throughout the colon (including the rectum) 3 minutes after it was ingested.

failure. Involvement of the gastrointestinal tract causes a profuse secretory diarrhea, abdominal cramping, nausea, and vomiting. There can be severe mucosal sloughing with resultant increased transit time through the gastrointestinal tract (Figs 10, 1 1). Isolated acute GVHD of the bowel is rare. Acute GVHD is staged according to the Severity and number oforgans involved. Minima! disease is usually not treated; severe disease can be treated with steroids and cyclosporine. Unfortunately, these drugs have immunosuppressive side effects. The length

of treatment depends on the time course of the disease, and some patients may continue to receive these drugs even after discharge from the hospital. Because patients with acute GVHD have a greater degree of immunodeficiency than unaffected patients, death is usually due to opportunistic infections rather than direct manifestations of the disease. The frequency

crease ent.

. The

pathogenesis

factorial.

U

RadioGraphics

U

Patzik

et a!

the

Pneumatosis

in bone

608

and

with

marrow

Steroid

severity

age

of acute

of the

GVHD

transplant

in-

recipi-

Intestinalis of pneumatosis transplant

therapy

intestinalis

recipients

may

Volume

be

11

is multi-

a significant

Number

4

12. Figures

12,

pneumatosis

13.

(12)

of the

Pneumatosis

large

intestinalis.

bowel

in a patient

Plain who

13. ofthe

radiograph

received

abdomen

an allogeneic

bone

shows

marrow

extensive

line’

transplant

r

3 weeks

pre-

viously. Despite the extent of the pneumatosis, this patient did not suffer any adverse clinical effects, and the pneumatosis intestinalis resolved without intervention or therapy. (13) Chronic GVHD ofthe skin in an infain. The hand has areas ofdry, scaling skin with cracks and fissures that may bleed. This severe dermatitis may

serve

factor

as a source

in the

roids

induce

in the

of superimposed

development atrophy

of the

may

into

the

12).

Infectious

even

or

agents

mucosal

of intramural

subserosal

may

subsequent

is detected

(Fig

contribute

to

intestinalis. intestinalis in development

retroperitoneal air or pneumoperitoneum, does not necessitate surgery or indicate grave prognosis. However, if pneumatosis intestinalis

gas

region

also

of pneumatosis of pneumatosis with

Ste-

aggregates resultant

dissection

submucosal

the development The presence itself,

tract;

allow

disease.

oflymphoid

gastrointestinal

defects

infection.

in the

temic infection or shock, tation of life-threatening an asymptomatic patient, nalis is probably oflittle

context

of

a

Chronic

S

GVHD

Chronic GVHD 30% of allogeneic Chronic GVHD gastrointestinal serosal

bles

surfaces,

it may be a manifesintestinal disease. In pneumatosis intesticlinical importance

(14).

and

a connective with

ciency. Treatment dude long-term and cyclosporine. therapy, infection

use

ofboth

tions

of the

most with

common chronic

upper

Recurrence

of disease

is another

it resem-

(Fig

long-lasting

13),

and

immunodefi-

of chronic GVHD may inof steroids, azathioprine, chronic

GVHD

and

respiratory

tract

are

late infections seen GHVD. The bacterial

gram-positive

organisms

and

tococcuspneumoniae

tion.

Clinically,

disorder

its

patients may have many episodes that can be fatal (15). Bacterial

usually

U DELAYED COMPLICATIONS A third major risk period begins approximately 3 months after engraftment. The most common delayed problem in patients with allogeneic transplants is chronic GVHD (15). The syndrome itself and its treatment cause an associated immunosuppression that increases the patient’s susceptibility to infec-

lung.

tissue

it is associated

As a result of sys-

occurs in approximately transplant recipients (4). involves the skin, oral mucosa, tract, liver, skeletal muscle,

of infecthe

in patients agents are such

as Stnep-

S auneus.

.

Recurrence of Disease Recurrence of disease usually occurs within 2 years of engraftment. This late complication is thought to be secondary to persistence of malignant cells, despite the pretransplantation cytoreductive

therapy.

delayed

complication.

July

1991

Patzik

et a!

U

RadioGrapbic.s

U

609

U CONCLUSION In the past decade, tion

has

become

treatment

an

for

all

its basic

varied

clinical

aspects

as well

that

may

used

disseminated

therapeutic makes

to become

complications

6.

It is being with

The growing transplantation

radiologists

transplantapromising

patients.

in patients

tumors. marrow

tial

marrow

important,

for many

experimentally

solid bone

bone

role of it essen-

familiar as with

7. 8.

with the

develop. 9.

REFERENCES

U 1.

2.

Barrett J. Worldwide bone marrow transplantation activity in the last decade: new strategies in bone marrow transplantation. New York: Wiley-Liss, 1991; 1-6. Gratwohl A. Bone marrow transplantation: indications and technique. Radiother Oncol

1990; 3.

18(supp

Clift RA, Petersen transplantation.

Sullivan

KM.

tion

Graft-versus-host

disease.

of

12.

marrow 13.

15.

U

RadioGrapbics

U

Patzik

et a!

BP, Abu-Yousef

M, Farner

transplantation.

Blood

R, LaBreque

1988;

71:

1432-1437.

14.

610

Transplanta-

D, Gingrich R. Doppler sonography: a noninvasive method for evaluation of hepatic venocclusive disease. AJR 1990; 154:721-724. WingardJR, Yen-Hung Chen D, Burns WI-I, et al. Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone

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Volume

11

Number

4