Release Date:  September 4, 1998


RFA:  HL-98-022

National Heart, Lung, and Blood Institute
National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  October 26, 1998
Application Receipt Date:  November 24, 1998



The Cellular Hematology Scientific Research Group, Division of Blood Diseases
and Resources, NHLBI, and the Hematology Program, Division of Kidney,
Urologic, and Hematologic Diseases, NIDDK, announce the availability of a
Request for Applications (RFA) on the above subject. The objective of this
initiative is to develop improved and novel preparative regimens that will
permit incompatible hematopoietic stem cell transplantation in immunized
recipients with hemoglobinopathies.  The possibility of successful stem cell
transplantation for hemoglobinopathies being performed where complete
myeloablation is not desirable and partial replacement of defective marrow may
be sufficient for clinical benefit needs to be explored.  The overall goal of
the initiative is to focus on approaches to enable successful stem
transplantation for hemoglobinopathies and minimize recipient morbidity and
mortality. It is important that the approaches proposed include the potential
to evolve into human clinical studies.  Such studies will undoubtedly improve
the morbidity and mortality associated with marrow and stem cell
transplantation for hemoglobinopathies.


The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This initiative is related to the priority
areas of maternal and infant health and cancer.  Potential applicants may obtain
a copy of "Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or Summary
Report:  Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone


Applications may be submitted by domestic and foreign, for-profit and
nonprofit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State or local governments, and eligible
agencies of the Federal government.  Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as Principal
Investigators.  Domestic applications may include foreign components. FOREIGN
INSTITUTIONS: Awards under this announcement may be made to foreign
institutions provided the application (1) is of high scientific merit and (2)
offers a special opportunity for furthering research programs through the use
of unusual talents, resources, populations, or conditions in other countries
which are not readily available in the United States or which augment existing
U.S. resources.  All current policies and requirements that govern the
research grant programs of the NIH will apply to grants awarded under this


This RFA will use the NIH individual research project grant (R01) mechanism of
support.  Newly independent investigators who may wish to consult with a
program representative (see INQUIRIES section) are encouraged to apply. 
Specific application instructions have been modified to reflect "MODULAR
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH.  The
modular grant concept establishes specific modules in which direct costs may
be requested as well as a maximum level for requested budgets.  Only limited
budgetary information is required under this approach.  The just-in-time
concept allows applicants to submit certain information only when there is a
possibility for an award.  It is anticipated that these changes will reduce
the administrative burden for the applicants, reviewers and Institute staff.

For this RFA, funds must be requested in $25,000 direct cost modules and a
maximum of ten modules ($250,000 direct costs) per year may be requested.  Any
necessary escalation must be included within the number of modules being 
requested.  Only limited budget information will be required and any budget
adjustments made by the Initial Review Group will be in modules of $25,000. 
Instructions for completing the Biographical Sketch have also been modified. 
In addition, Other Support information and the application Checklist page are
not required as part of the initial application.  If there is a possibility
for an award, necessary budget, Other Support and Checklist information will
be requested by NHLBI or NIDDK staff following the initial review.  The
APPLICATION PROCEDURES section of this RFA provides specific details of 
modifications to standard PHS 398 application kit instructions.

Applicants, who will plan and execute their own research programs, are
requested to furnish their own estimates of the time required to achieve the
objectives of the proposed research project.  Up to four years of support may
be requested.  At the end of the official award period, renewal  applications
may be submitted for peer review and competition for support through the
regular grant program of the NHLBI and NIDDK.  It is anticipated that support
for the present program will begin August 1999.  Administrative adjustments in
project period or amount of support may be required at the time of the award. 
Since a variety of approaches would represent valid responses to this
announcement, it is anticipated that there will be a range of costs among
individual grants awarded.  All current policies and requirements that govern
the research grant programs of the NIH will apply to grants awarded in
connection with this RFA.


It is anticipated that for fiscal year 1999, $2 million total costs will be
available for the first year of support for this initiative by the NHLBI. 
Award of grants pursuant to this RFA is contingent upon receipt of such funds
for this purpose.  It is anticipated that approximately five to six new grants
will be awarded under this program.  The NIDDK plans to allocate an additional
$1 million in total costs for the first year of support and plans to fund up
to three applications.  Applicants may request up to four years of support.
The specific number to be funded will, however, depend on the merit and scope
of the applications received and on the availability of funds.  Direct costs
will be awarded in modules of $25,000, less any overlap or other necessary
administrative adjustments.  Facilities and administrative costs will be
awarded based on the negotiated rates.  If collaborative arrangements involve
subcontracts with other institutions, Ms. Jane R. Davis of the NHLBI Grants
Operations Branch (telephone: (301) 435-0166) should be consulted regarding
procedures to be followed.



The objective of this initiative is to develop improved and novel preparative
regimens that will permit incompatible hematopoietic stem cell transplantation
in immunized recipients with hemoglobinopathies.  The possibility of
successful stem cell transplantation for hemoglobinopathies being performed
where complete myeloablation is not desirable and partial replacement of
defective marrow may be sufficient for clinical benefit needs to be explored. 
The overall goal of the initiative is to focus on approaches to enable
successful stem cell transplantation for hemoglobinopathies and minimize
recipient morbidity and mortality.  It is important that the approaches
proposed include the potential to evolve into human clinical studies.  Such
studies will undoubtedly improve the morbidity and mortality associated with
marrow and stem cell transplantation for hemoglobinopathies.

Sickle cell disease is a complex syndrome with multiple organ system
disturbances brought about through the interplay of genetic, humoral,
vascular, and environmental factors.  The clinical course can be one of abrupt
and insidious exacerbations and remissions, often migratory and repetitive.
These events may result in impairment of function, permanently damaged organs,
and ultimately death. Although there is wide variability in the clinical
expression of sickle cell disease, ranging from mild to very severe, this
complex set of clinical manifestations is experienced by most patients. 
Recent progress has now enabled clinicians to offer patients with sickle cell
disease treatment that extends beyond traditional supportive care (1). 
However, these therapies are not free from risk and are not appropriate for
every patient. Transfusions carry risks of alloimmunization, iron overload,
and transfusion transmitted infections. In the absence of effective iron
chelation therapy, iron overload leads to numerous complications including
delayed or absent sexual development, diabetes mellitus, cirrhosis, cardiac
arrhythmias, and congestive heart failure.  Recently, histocompatible
hematopoietic stem cell transplantation for sickle cell disease was
demonstrated to have curative potential, a feature which distinguishes it from
ameliorative therapies such as hydroxyurea and chronic red cell blood
transfusions (2,3).  Thus, HLA-matched stem cell transplantation for sickle
cell disease in Europe and the U.S. has clearly benefitted a selected group of
patients experiencing recurrent neurological, pulmonary, and vaso-occlusive
events.  However,  the morbidity and mortality  associated with
transplantation has led most patients with hemoglobinopathies (see Cooley's
anemia below) and their physicians in the United States to pursue alternative
therapies which only ameliorate the disease.  An additional confounding factor
in selecting patients for marrow transplantation is that there are no reliable
predictors to identify the patients who are at the greatest risk of
progressing to significant morbidity and mortality.

Cooley's anemia, another genetic blood disease, results in an inadequate
production of hemoglobin, the essential oxygen-carrying substance in blood. 
This causes severe anemia that begins shortly after birth.  As a group,
thalassemic disorders comprise one of the most common single-gene genetic
diseases worldwide.  In the United States, thalassemia mainly affects specific
ethnic groups, including people of Mediterranean, Middle Eastern, African,
Southeast Asian, Chinese, and Asiatic Indian origin.  Individuals affected
with Cooley's anemia require frequent and lifelong blood transfusions to
sustain life.  Because there are no natural means for the body to eliminate
iron, the iron contained in the transfused red blood cells builds up over many
years and eventually becomes toxic to tissues and organ systems.  This excess
iron must be removed from Cooley's anemia patients or they may not survive
beyond the second decade of life.  To accomplish this, patients must use the
iron-binding or chelating drug, deferoxamine, that is administered for about
ten hours every day by pumping it through a needle inserted either under the
skin or intravenously.  The addition of chelation therapy with deferoxamine to
the treatment of Cooley's anemia has dramatically improved the outcome for
affected patients. With regular chelation therapy, the accumulation of
excessive iron can be prevented. Studies have demonstrated that well chelated
patients have normal or only modest increases in liver iron, improved growth,
normal sexual development, and most importantly, a markedly reduced chance of
developing iron induced heart disease. Therefore, well chelated patients have
a greater chance of achieving long-term survival.  However, compliance with
this demanding treatment regimen remains a difficult challenge for many
patients.  The majority of patients with Cooley's anemia report a negative
impact of this onerous regimen on their quality of life.  Thus, some patients
are unable to continue this treatment during late childhood and adolescence. 
In the United States, the inability of patients with Cooley's anemia to comply
with prolonged subcutaneous or intravenous infusions represents the primary
obstacle to the reduction of body iron and is the reason some patients still
die of the complication of iron overload.

Bone marrow transplantation is used frequently in other countries as an
alternative approach to the treatment of patients with sickle cell disease and
Cooley's anemia (4,5). For patients undergoing transplantation with bone
marrow from a matched sibling, the probability of thalassemia-free survival is
reported to be between 75% and 95%, depending upon their disease status at the
time of transplantation.  The outcome depends on several factors including the
severity of liver damage, the degree of iron overload, and the transplant

Due to the morbidity and mortality associated with bone marrow
transplantation, few hemoglobinopathy patients have received this treatment in
the United States.  Thus, the development of novel nontoxic or minimal
myeloablative conditioning with the aim of creating stable donor-host mixed
chimerism and decreasing the toxicities associated with transplantation is
central to this RFA.  Murine studies indicate significant levels of
engraftment following 100 cGy whole body irradiation.  This level of
myeloablation is associated with minimal myelotoxicity (6).  Studies by
Ildstad and colleagues (7) indicate that relatively nontoxic treatment can
lead to high rates of chimerism in mismatched murine allogeneic models.  These
data can potentially be extrapolated to humans.  Recent data, in older
patients with chronic lymphocytic leukemia (CLL), suggest that stable
allochimerism can be created with relatively nontoxic preparative regimens for
treatment of hemoglobinopathies (8).  Walters and colleagues reported sickle
cell disease patients with stable mixed chimerism for two years who are free
of symptoms (9).  For hemoglobinopathy patients, split chimerism may produce
stabilization/cure without some of the toxicities associated with complete
donor lymphohematopoietic engraftment.

Since most patients with hemoglobinopathies have normal immune systems and
would have been transfused, preparative regimens that will permit
histoincompatible hematopoietic stem cell engraftment in immunized hosts
should be developed.  More information is needed on different "minimal"
ablative regimens for obtaining split chimerism, on approaches for maximizing
tolerance induction, on post-transplant therapy to minimize the risk of acute
and chronic graft-versus-host disease and on stem cell and facilitator cell
doses and roles in such engraftment.  In addition, further information is
needed on host treatment which might modify the degree of chimerism.  The
results of these studies could significantly impact the treatment of
hemoglobinopathies and have broader implications for the field of
transplantation and treatment of autoimmune diseases such as lupus,
scleroderma, rheumatoid arthritis, diabetes and multiple sclerosis.  The above
examples of research approaches are not meant to be all inclusive or
restrictive.  Prospective applicants are encouraged to develop their own ideas
of research on which to focus to address the goals of the RFA.  Proposals
which include basic and preclinical models that will evolve into future human
clinical studies would be responsive to this RFA.


Upon initiation of the program, the NHLBI and the NIDDK will sponsor annual
meetings to encourage the exchange of information among investigators who
participate in this program.  In the preparation of the budget for the grant
application, applicants should REQUEST ADDITIONAL TRAVEL FUNDS for one meeting
each year to be held in Bethesda, Maryland.  Applicants should also include a
statement in the applications indicating their willingness to participate in
such meetings.


It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided that inclusion is
inappropriate with respect to the health of the subjects or the purpose of
research.  This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43) and supersedes and strengthens the
previous policies (Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations) which have been
in effect since 1990.  The policy contains some new provisions that are
substantially different from the 1990 policies.  All investigators proposing
research involving human subjects should read the "NIH Guidelines for
Inclusion of Women and Minorities as Subjects in Clinical Research", which
have been published in the Federal Register of March 28, 1994 (FR 59
14508-14513), and in the NIH GUIDE FOR GRANTS AND CONTRACTS of March 18, 1994,
Volume 23, Number 11.

Investigators may obtain copies from these sources or from the program staff
or contact person listed below.  Program staff may also provide additional
relevant information concerning the policy.


It is the policy of the NIH that children (i.e., individuals under the age of
21) must be included in all human subjects research, conducted or supported by
the NIH, unless there are specific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for receipt
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at the following URL


Prospective applicants are asked to submit, by October 26, 1998, a letter of
intent that includes a descriptive title of the proposed research, the name,
address, and telephone number of the Principal Investigator, the identities of
other key personnel and participating institutions, and the number and title
of the RFA in response to which the application may be submitted.  Although a
letter of intent is not required, is not binding, and does not enter into the
review of a subsequent application, the information that it contains allows
staff to estimate the potential review workload and to avoid conflict of
interest in the review.  The letter of intent is to be mailed, or faxed, to:

Dr. C. James Scheirer
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7220, MSC 7924
Bethesda, MD  20892-7924
Telephone:  (301) 435-0266
FAX:  (301) 480-3541


Applications are to be submitted on the research grant application form PHS
398 (rev. 5/95).  Application kits are available at most institutional offices
of sponsored research and may be obtained from the Division of Extramural
Outreach and Information Resources, National Institutes of Health, 6701
Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267,
email:  Use the conventional format for research grant
applications and ensure that the points identified in the section on REVIEW
CONSIDERATIONS are fulfilled.


Sample budgets and justification page will be provided upon request or
following the submission of a letter of intent.

The total direct costs must be requested in accordance with the program
guidelines and the modifications made to the standard PHS 398 application
instructions described below:

As a reminder, Item 7 should be completed to indicate Modular Direct Costs
requested and Item 8 should reflect Total Costs (Modular Direct plus F&A

Do not complete Form Page 4 of the PHS 398 (rev 5/95).  It is not required nor
will it be accepted at the time of application.

Do not complete the categorical budget tables on Form page 5 of the PHS 398
(rev. 5/95).  Only the requested total direct costs line for each year must be
completed based on the number of $25,000 modules being requested.  Applicants
may not request a change in the amount of each module.  A maximum of ten
modules ($250,000 direct costs) per year may be requested and each applicant
may request up to four years of support for this RFA.  Direct cost budgets
will remain constant throughout the life of the project (i.e., the same number
of modules requested for all budget periods).  Any necessary escalation should
be considered when determining the number of modules to be requested. 
However, in the event that the number of modules requested must change in any
future year due to the nature of the research proposed, appropriate
justification must be provided.  Total Direct Costs for the Entire Proposed
Project Period should be shown in the box provided.


Budget justifications should be provided under "Justifications" on Form Page 5
of the PHS 398.

List the names, role on the project and proposed percent effort for all
project personnel (salaried or unsalaried)and provide a narrative
justification for each person based on his/her role on the project.

Identify all consultants by name and organizational affiliation and describe
the services to be performed.

Provide a general narrative justification for individual categories
(equipment, supplies, etc.) required to complete the work proposed.  More
detailed justifications should be provided for high cost items.  Any large
one-time purchases, such as large equipment requests, must be accommodated
within these limits.  No specific costs for items or categories should be

CONSORTIUM/CONTRACTUAL COSTS - If collaborations or subcontracts are involved
that require transfer of funds from the grantee to other institutions, it is
necessary to establish formal subcontract agreements with each collaborating
institution.  A letter of intent from each collaborating institution should be
submitted with the application.  Only the percentage of the
consortium/contractual TOTAL COSTS (direct and indirect) relative to the total
DIRECT COSTS of the overall project needs to be stated at this time.  The
following example should be used to indicate the percentage cost of the
consortium, "The consortium agreement represents 27% of overall $175,000
direct costs requested in the first year".  A budget justification for the
consortium should be provided as described in the "Budget Justification"
section above (no Form Page 5 required for the consortium).  Indicate whether
the consortium will be in place for the entire project period and identify any
future year changes in the percentage relative to the parent grant.

If there is a possibility for an award, the applicant will be requested to
identify actual direct and facilities and administrative costs for all years
of the consortium.  Note that total subcontract costs need not be calculated
in $25,000 modules.  However, when subcontract funds are added to the parent
grant budget, the total direct cost amount must be included in the number of
$25,000 modules requested.  If clarification of the policy is needed, contact
Ms. Jane R. Davis (under INQUIRIES).

BIOGRAPHICAL SKETCH - A biographical sketch is required for all key personnel,
following the modified instructions below.  Do not exceed the two-page limit
for each person.

- Complete the educational block at the top of the form page; - List current
position(s) and those previous positions directly relevant to the application;

- List selected peer-reviewed publications directly relevant to the proposed
project, with full citation;

- The applicant has the option to provide information on research projects
completed and/or research grants participated in during the last five years
that are relevant to the proposed project.


- Do not complete the "Other Support" pages (Form Page 7).  Selected other
support information relevant to the proposed research may be included in the
Biographical Sketch as indicated above.  Complete Other Support information
will be requested by NHLBI staff if there is a possibility for an award.


- No "Checklist" page is required as part of the initial application.  A
completed Checklist will be requested by NHLBI or NIDDK staff if there is a
possibility for an award.

- The applicant should provide the name and phone number of the individual to
contact concerning fiscal and administrative issues if additional information
is necessary following the initial review.

Applications not conforming to these guidelines will be considered
unresponsive to this RFA and will be returned without further review.

Applicants from institutions that have a General Clinical Research Center
(GCRC) funded by the  NIH National Center for Research Resources may wish to
identify the GCRC as a resource for conducting the proposed research.  If so,
a letter of agreement from either the GCRC program director or principal
investigator could be included with the application.

The RFA label available in the PHS 398 (rev. 5/95) application form must be
affixed to the bottom of the face page of the application.  Failure to use
this label could result in delayed processing of the application such that it
may not reach the review committee in time for review.  In addition, the RFA
title and number must be typed on line 2 of the face page of the application
form and the YES box must be marked.

Send or deliver the completed application and three signed, exact photocopies
of it to the following, making sure that the original application with the RFA
label attached is on top:

6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

Send an additional two copies of the application to the Dr. Scheirer at the
address listed under LETTER OF INTENT.  It is important to send these two
copies at the same time as the original and three copies are sent to the
Center for Scientific Review (CSR).  Otherwise the NHLBI cannot guarantee that
the application will be reviewed in competition for this RFA.

Applications must be received by November 24, 1998.  If an application is
received after that date, it will be returned to the applicant without review. 
The CSR will not accept any application in response to this RFA that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application.  The CSR will not accept any
application that is essentially the same as one already reviewed. This does
not preclude the submission of substantial revisions of applications already
reviewed, but such applications must include an introduction addressing the
previous critique.


Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NHLBI and NIDDK.  Incomplete and/or non-responsive
applications will be returned to the applicant without further consideration. 
Applications that are complete and responsive to the RFA will be evaluated for
scientific and technical merit by an appropriate peer review group convened by
the NHLBI in accordance with the standard NIH peer review procedures.  As part
of the initial merit review, all applications will receive a written critique
and undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of applications under review,
will be discussed, assigned a priority score, and receive a second level
review by the appropriate national advisory council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. In
judging the likelihood that the proposed research will have a substantial
impact on the pursuit of these goals and those of the RFA, the reviewers will
address each of the listed criteria, and consider them in assigning the
overall priority score, weighting them as they feel appropriate for each
application.  Please note that your grant application may not need to be
strong in all categories to be judged likely to have a major scientific impact
and thus deserve a high priority score.  For example, an investigator may
propose to carry out important work, that by its nature is not innovative but
is essential to move a field forward.

(1) Significance.  Does the study address an important problem?  If the aims
of the application are achieved, how will scientific knowledge be advanced? 
What will be the effect of these studies on the concepts or methods that drive
this field?

(2) Approach.  Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project?  Does the applicant acknowledge potential problem areas and consider
alternative tactics?

(3) Innovation.  Does the project employ novel concepts, approaches or
methods?  Are the aims original and innovative?  Does the project challenge
existing paradigms or develop new methodologies or technologies?

(4) Investigator.  Is the investigator appropriately trained and well suited
to carry out this work?  Is the proposed study appropriate to the experience
level of the principal investigator and other researchers (if any)?

(5) Environment.  Does the scientific environment in which the work will be
performed contribute to the probability of success?  Do the proposed
experiments take advantage of unique features of the scientific environment or
employ useful collaborative arrangements?  Is there evidence of applicant
institutional support?

In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities, and their
subgroups, and children as appropriate for the scientific goals of the
research.  Plans for the recruitment and retention of subjects will also be

o  The reasonableness of the proposed budget and duration in relation to the
proposed research.

o  The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project
proposed in the application.

The initial review group will also examine the provisions for the protection
of human and animal subjects and the safety of the research environment.

The personnel category will be reviewed for appropriate staffing based on the
requested percent effort.  The direct costs budget request will be reviewed
for consistency with the proposed methods and specific aims.  Any budgetary
adjustments recommended by the reviewers will be in $25,000 modules.  The
duration of support will be reviewed to determine if it is appropriate to
ensure successful completion of the requested scope of the project.


The anticipated date of award is August 1999.  Funding decisions will be made
on the basis of scientific and technical merit as determined by peer review,
program needs and balance, and the availability of funds.

Awards in response to this RFA will be made to foreign institutions only for
research of very unusual merit, need, and promise, and in accordance with PHS
policy governing such awards.  Designated funding levels are subject to change
at any time prior to award, due to unforeseen budgetary, administrative and/or
scientific developments.


Inquiries concerning this RFA are encouraged.  Potential applicants should
request a copy of the full RFA, which will include sample budget pages as
previously stated.  The opportunity to clarify any issues or questions from
potential applicants is welcome.

Inquiries regarding programmatic issues may be directed to:

Dr. Helena O. Mishoe
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 10156
Bethesda, MD  20892-7950
Telephone:  (301) 435-0050
FAX:  (301) 480-0868

Dr. David G. Badman
Division of Kidney, Urologic, and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS-13C, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-7717
FAX:  (301) 480-3510

Direct inquiries regarding fiscal matters to:

Ms. Jane R. Davis
Grants Management Office
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, MSC 7926
Bethesda, MD  20892-7926
Telephone:  (301) 435-0166
FAX:  (301) 480-3310

Ms. Aretina Perry-Jones
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AN-38B, MSC 6600
Bethesda  MD  20892-6600
Telephone:  (301) 594-8862


This program is described in the Catalog of Federal Domestic Assistance Nos.
93.839 and 93.848.  Awards will be made under the authority of the Public
Health Service Act, Section 301 (42 USC 241) and administered under PHS grant
policies and Federal regulations, most specifically 42 CFR Part 52 and 45 CFR
Part 74.  This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or to Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a
smoke-free workplace and promote the non-use of all tobacco products.  In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking
in certain facilities (or in some cases, any portion of a facility) in which
regular or routine education, library, day care, health care or early
childhood development services are provided to children.  This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.


1.  Charache S; Terrin ML; Moore RD; Dover GJ; Barton FB; Eckert SV; McMahon
RP; Bonds DR:  Effect of hydroxyurea on the frequency of painful crises in
sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in
Sickle Cell Anemia [see comments] N Engl J Med May 18;332(20):1317-22, 1995.

2.  Olivieri NF, et al: Hydroxyurea in children with sickle cell disease:
impact on splenic function and compliance with therapy. J Pediatr Hematol
Oncol. Jan; 20(1): 26-31, 1998.

3.  Rana S, Houston PE, Surana N, Shalaby-Rana EI, Castro OL:  Discontinuation
of long-term transfusion therapy in patients with sickle cell disease and
stroke. J Pediatr Nov;131(5):757-760, 1997.

4.  Vermylen C, et al: Bone marrow transplantation for sickle cell anemia.
Curr Opin Hematol. Mar; 3(2): 163-166, 1996 Review.

5.  Lucarelli G:  Bone marrow transplantation for thalassemia. J Intern Med
Suppl; 740:49-52, 1997.

6.  Stewart FM, Zhong, S, Wuu J, Hsieh C, Nilsson SK, Quesenberry PJ:
Lymphohematopoietic engraftment in minimally myeloablated hosts. Blood; May
15;91(10):3681-7, 1998.

7.  Colson YL, Li H, Boggs SS, Patrene K, Johnson PC, Illdstad ST: Durable
mixed allogeneic chimerism and tolerance by a non-lethal radiation-based
cytoreductive approach.  J Immuno157: 2820, 1996.

8.  Montserrat E: New therapeutic issues in CLL.  Hematol and Cell therapy 39:

9.  Walters MC; Patience M; Leisenring W; Eckman JR; Scott JP; Mentzer WC;
Davies SC; Ohene-Frempong K; Bernaudin F; Matthews DC; Storb R; Sullivan KM:
Bone marrow transplantation for sickle cell disease [see comments] N Engl J
Med Aug 8;335(6):369-76, 1996.

Return to Volume Index

Return to NIH Guide Main Index

Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS) - Government Made Easy

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.