PNH Patient Brochure

TRUTH:
You are not alone.
Although PNH is rare,
support is not hard to
come by. Call OneSource™
at 1.888.765.4747.
An Alexion Nurse Case
Manager can help answer
your questions about PNH
and connect you with
other people who have
PNH, just like you.
Taking a closer look.
And taking control of PNH.
Paroxysmal nocturnal hemoglobinuria (PNH) is a
serious disease. And living with it can be scary. You
may feel lost and alone. But with the right tools and
support, you can take control.
It starts with the right information.
If you have been diagnosed with PNH,
you probably have a lot of questions.
What is PNH?
What causes PNH?
What are the symptoms?
How can I manage PNH?
How can I find help?
2
I see PNH
differently.
Use this brochure to take a closer look at PNH. Find
out how it works — and what you can do about it. It
just might change the way you see PNH.
“At first I was really scared.
But when I met someone else
who was managing her PNH,
I realized I could take control.”
– Kathy*
As you are reading:
Find underlined terms in the Glossary on pages 26 and 27.
*Fictitious patient and account. Adapted from real patient stories.
3
Building your
healthcare team.
With rare diseases like PNH,
it’s common for doctors to
take a team approach. You
and your doctor may choose
to work with someone
who has more in-depth
experience — especially if
you are the only one with
PNH your doctor is treating.
There are doctors who
conduct research in PNH,
or who care for a greater
number of people who have
it. Speak with your doctor
about how you could benefit
by seeing a doctor with this
kind of experience from time
to time.
?
Have more questions?
Call OneSource™ at
1.888.765.4747 to speak
one-to-one with an Alexion
Nurse Case Manager.
4
What is PNH?
Start learning — and change
the way you see PNH.
Find answers to your questions here.
PNH is a serious and unpredictable disease. It comes
with a wide range of signs and symptoms that are
often similar to other diseases. As a result, everyone
experiences PNH differently, making it tough to
diagnose. But PNH is also treatable and there’s a lot
you can do. Understanding the disease is the first step
toward taking control.
What is PNH?
PNH is an acquired disease that destroys an important
part of your blood: the red blood cells. Red blood
cells develop in your bone marrow. They’re important
because they help deliver oxygen and remove waste
from your body.
What is PNH?
Who gets PNH?
PNH is a rare disease, but
that doesn’t mean you’re
alone. It affects about 8,000
to 10,000 people in North
America and Western Europe.
s Both men and women
can get PNH
s PNH occurs across
all races
What does PNH do?
With PNH, some or all of your red blood cells are
destroyed. This is called hemolysis. In PNH, it happens
constantly and at high rates, which could put you at
risk. Hemolysis is the main cause of the major health
problems in PNH, including the most severe.
s In PNH, hemolysis happens all the time
s Ongoing hemolysis happens to people with PNH
because some or all of their red blood cells are
missing an important protective protein
s Your body’s defense system attacks red blood cells
without this protein
s PNH is progressive. This means your disease can
get worse over time, increasing your risk of major
PNH health problems
s PNH can occur at any
age; the average age at
diagnosis is in the early 30s
Defining clone size.
You may have heard your
doctor use the term “clone
size.” This refers to the
percentage of red blood cells
in your body that are affected
by PNH. A larger clone size
means you have more PNH
cells, but even patients who
have a small clone size can
have symptoms that may
greatly limit their lives, such
as fatigue, stomach pain,
chest pain, shortness of
breath, and dark-colored urine.
What is PNH? 5
I see PNH
differently.
“Once I learned the facts
about PNH, it was easier
to understand and manage.”
– Dan*
Other bone marrow
failure disorders.
Aplastic anemia (AA) and
myelodysplastic syndromes
(MDS) are also bone marrow
failure disorders. Unlike PNH,
AA and MDS don’t destroy
red blood cells. Instead, AA
and MDS cause your body
to make fewer healthy ones.
Both these diseases, as well
as PNH, can lead to anemia,
but in different ways. If
you have AA or MDS and
PNH, ask your doctor about
treatment options for each
of these conditions.
6 What is PNH?
What are the risks of having PNH?
The biggest risk of PNH is that you cannot always see or
feel its effects. So serious health risks can take you by
surprise. If left untreated, PNH can lead to:
Blood clots:
These form when parts of your body’s blood
clump together. Clots can block veins and
arteries and lead to heart attack, stroke, and
organ damage, as well as other problems.
Kidney damage:
Get to the bottom
of blood clots.
Hemolysis can put you at
greater risk of having a
blood clot.
With PNH, blood clots:
s Can occur at any time,
and can happen with any
size clone
Almost /3 of people with PNH have chronic
kidney disease, a life-threatening condition.
s Can be life threatening —
even the first time you
experience one
Fatigue:
s Occur most often in the
legs and lungs
2
Hemolysis affects the way oxygen gets
delivered throughout your body. This can
make you feel weak and tired to the point
where once-normal, everyday activities
become a struggle.
Lung problems:
Patients with smaller clone
sizes can still develop blood
clots that can lead to more
serious and life-threatening
health problems.
Speak with your doctor about
finding a treatment to reduce
your risk of blood clots.
Almost 1/2 of PNH patients have signs
of lung problems. Lung problems can be
caused by pulmonary hypertension. This
can lead to shortness of breath and other
serious health problems.
*Fictitious patient and account. Adapted from real patient stories.
What is PNH? 7
PNH
What’s in a name?
PNH stands for
paroxysmal nocturnal
hemoglobinuria. The
disease was called this
before much was known
about it. Today, more is
known about the disease,
but doctors still call it
PNH. So the name is a
little misleading.
Here’s why:
s Paroxysmal
MYTH: The disease
comes and goes
TRUTH: PNH is always present
and hemolysis is always
happening, whether it flares
up or not
s Nocturnal
MYTH: PNH happens at night
TRUTH: The effects of
PNH don’t just happen at
night — they happen all
the time
s Hemoglobinuria
MYTH: Hemoglobin found in
urine is the main part of PNH
diagnosis
TRUTH: Not everyone with PNH
has dark-colored urine when
diagnosed, though most will
experience it at some point
8 What is PNH?
What can I do about it?
PNH can be life threatening. But with the right
treatment, people with PNH can live long,
full lives. It’s important to start treatment
early — and aggressively. By working closely with
your doctor, you may be able to keep the risks of
PNH at bay.
Together, you and your doctor will track:
s Your symptoms: Stomach pain, difficulty
swallowing, shortness of breath, fatigue, and
erectile dysfunction, among others
s Your lab results: Lactate dehydrogenase
(LDH) as a measure of hemolysis, hemoglobin
(Hgb) levels, and others
There’s no one sign, symptom, or lab result
that defines PNH. You may feel fine, even when
your lab results show problems. To get the full
story, your signs and symptoms — as well as your
lab results — need to be watched closely. Find
helpful tools in the back of this brochure or visit
PNHSource.com/patients/helpful-resources.
Checkup: Quick facts about PNH.
s PNH is serious. It starts with your blood, but it can affect your entire body
s PNH is dangerous. If you don’t take care of PNH, it can lead to serious health
problems, including some that can be life threatening
s PNH is constant. Even though you can’t see it, hemolysis is always happening
s PNH is treatable. In fact, treatment is vital. And there are options. Speak with your
doctor to find out what’s right for you
What is PNH? 9
Hemolysis: The threat you cannot see.
LDH: Putting
hemolysis to
the test.
Lactate dehydrogenase
(LDH) is an enzyme found
inside red blood cells. LDH
measures hemolysis. If you
have high levels of it in your
bloodstream, it means a lot
of your red blood cells have
been destroyed. Your doctor
can check for LDH through
a simple blood test. Testing
your LDH regularly is a vital
part of taking control of
your disease.
Taking action is key to fighting PNH.
Ongoing hemolysis is the root cause of the signs,
symptoms, and serious health problems of PNH.
It happens when red blood cells burst. With PNH,
hemolysis is always happening — even if you can’t see
or feel it.
Why is hemolysis so bad?
When red blood cells burst, they release hemoglobin.
Hemoglobin is good for the body when it’s inside your
red blood cells. When it’s outside, it is very dangerous
and can harm your body in many ways. Over time, it
is very dangerous and can build up and cause serious
health problems that are hard to predict.
These health problems can include:
s Kidney failure
s Blood clots
s Stroke
Support is just a
phone call away.
Call OneSource™ at
1.888.765.4747 for more
information about PNH
and personalized support
from an Alexion Nurse
Case Manager.
10 What causes PNH?
s Heart attack
s Damage to organs such as your liver, brain,
and lungs
You cannot always see or feel hemolysis, which
makes it tough to manage. The results of it often
can affect the way you feel and live your life. Left
untreated, hemolysis can make you feel very tired
and weak.
It can also lead to signs and symptoms like:
s Fatigue
s Impaired quality of life
s Trouble swallowing
s Stomach pain
s Shortness of breath
s Dark-colored urine
s Erectile dysfunction (ED)
Why am I so tired?
In PNH, there are actually
two causes of fatigue:
hemolysis itself, which is
the main cause of fatigue,
and the anemia that’s
caused by hemolysis.
Fatigue is often worse than
the amount of anemia you
have, as measured by your
hemoglobin level.
If you have AA or MDS and
PNH, you may also have
anemia caused by these
disorders. Unlike PNH, the
anemia associated with AA
and MDS is caused by poor
red blood cell production
by the bone marrow.
Speak with your doctor
about treating hemolysis,
as well as different options
to treat AA or MDS.
Checkup: Quick facts about hemolysis.
s (EMOLYSISISTHEBURSTINGOFREDBLOODCELLS
s )N0.(HEMOLYSISISALWAYSHAPPENING
s /NGOINGHEMOLYSISCANLIMITTHEWAYYOULIVEANDCAUSESERIOUS
health problems such as heart attack or stroke
s !SIMPLEBLOODTESTFOR,$(LEVELSCANTELLYOUTHELEVELS
of your hemolysis
s #ONTROLLINGHEMOLYSISISTHEKEYTOCONTROLLING0.(
What causes PNH? 11
What causes PNH?
How will I know hemolysis
is happening?
What to look for with PNH.
MYTH:
My PNH is only
bad when I don’t
feel well.
With PNH, you can have
serious health problems
even if you feel fine. Be
aware of how you’re feeling
and let your doctor know.
This will help you both
manage your PNH in the
best way possible.
12 What are the symptoms?
Know yourself. Know your symptoms.
The signs and symptoms of PNH can be silent and
unpredictable. They affect everyone differently, and
they can change from day to day. Even when you can’t
see or feel symptoms, you can still be at risk of serious
health problems.
Symptoms you can see or feel.
Fatigue:
s
s
s
s
s
Tiredness
Difficulty performing
daily activities
Trouble concentrating
Dizziness
Weakness
Pain:
s
s
s
Stomach pain
Leg pain or swelling
Chest pain
Back pain
s
s
s
s
s
Dark-colored urine
Shortness of breath
Difficulty swallowing
Yellowing of the skin
and/or eyes
Erectile
dysfunction (ED)
What are the symptoms?
s
Other signs and
symptoms:
PNH is just like an
iceberg — what you
can’t see or feel can
hurt you the most.
TRUTH:
Less hemolysis can
lead to better health.
Blood clots
Kidney disease
Because most of the
dangers of PNH are caused
by ongoing hemolysis,
lowering it is a big part of
treatment. Speak with your
doctor about what you can
do to make this happen.
Damage to your organs
Stroke
Heart attack
Signs you may not always see or feel.
What are the symptoms? 13
How to speak with your doctor.
It’s easier to find success with PNH when you know
how to speak with your doctor. When you talk about
how you’re feeling, be sure to give your doctor the
whole story.
What: Describe all of your symptoms, even if you don’t
think they’re related to your PNH.
I see PNH
differently.
“For a long time I felt fine and
just ignored my PNH. I know
better now.”
– Abby*
When: When did they start? Do you feel them all the
time or just in certain situations?
Where: Show your doctor where on your body you’re
feeling the symptoms the most.
How much: Use a scale of 1 to 5 to describe how
intense your symptoms are.
Always there through
the ups and downs.
Call OneSource™ at
1.888.765.4747 to get
personalized support and
encouragement from a
registered nurse as you
manage your PNH.
14 What are the symptoms?
Giving details about your symptoms will help both you
and your doctor get the most out of each visit.
The new “normal.”
When you deal with PNH
every day, you can start
to get used to feeling its
symptoms. They may even
start to feel “normal.” That’s
why it’s important to track
your signs and symptoms, so
you can tell if they’re getting
worse over time. Speak with
your doctor about treatment
options — you shouldn’t have
to feel like being sick is normal.
Symptom tracking,
made easy.
Record your symptoms and
track your lab results, including
LDH levels, with the PNH
Symptoms Checkup Chart
from OneSource. Using this
helpful tool can help you and
your doctor monitor PNH—
call 1.888.765.4747 or visit
PNHSource.com/patients/
helpful-resources to get
yours today.
Checkup: Quick facts about PNH signs and symptoms.
s .OTEVERYONEWITH0.(HASTHESAMEEXPERIENCEORFEELSTHESAMEWAY
s 4HESYMPTOMSYOUCANTSEEORFEELCANBETHEMOSTDANGEROUS
s 9OUMAYFEELFINEBUTSTILLHAVESERIOUSHEALTHPROBLEMS
s +EEPTRACKOFYOURSIGNSANDSYMPTOMSANDSHARETHEMWITHYOURDOCTOR
*Fictitious patient and account. Adapted from real patient stories.
What are the symptoms? 15
MYTH:
I only need to track
my hemoglobin.
Hemoglobin is used to
measure anemia, a common
symptom of PNH. Anemia
is also a symptom of
other bone marrow failure
disorders, such as AA and
MDS. When hemoglobin
is tested, it’s hard to tell
which disease is causing
the results. To measure
hemolysis, the underlying
cause of PNH health
problems (including anemia),
you need to track your LDH.
Keep in mind what’s out of sight.
Track your signs, symptoms, and
lab results.
With PNH, your signs and symptoms only tell part of the
story. They can’t always tell you what’s going on inside
your body. Your signs and symptoms — combined with
lab results — give you and your doctor the full story of
your PNH.
Know your signs and symptoms.
Find support every
step of the way.
Call OneSource™ at
1.888.765.4747 to find
helpful information and
personalized support from
a registered nurse as you
manage your PNH.
When you track your signs and symptoms over time, you
and your doctor can be more aware of changes in your
health. So take note of how you’re feeling and share it with
your doctor. And remember, always contact your doctor if
you have any sudden changes to your health. Find helpful
tools in the back of this brochure or visit
PNHSource.com/patients/helpful-resources
for online resources and downloads.
Know your numbers.
There are a number of important lab tests that can help
tell you and your doctor how your PNH is progressing.
16 How can I manage PNH?
You can help your
doctor — help you.
How can I manage PNH?
s Lactate dehydrogenase (LDH): Frequent testing
of your LDH is an important part of PNH
management. This will give you and your doctor
an idea of how much hemolysis is going on in
your body. By tracking LDH levels over time, you
and your doctor can check your progress. Also,
your LDH levels can tell your doctor if you might
be at risk for serious health problems
Visit PNHSource.com/
patients/helpful-resources
to download a Lab Tracker
and a PNH Symptom
Checkup Chart. They’ll help
you and your doctor watch
your signs and symptoms
and your lab test results,
so you can get more out of
each doctor’s visit.
Along with LDH and other tests, your doctor may
also check:
s Red blood cells (RBCs): These deliver oxygen
and remove waste from your body. Tests will
check the amount in your blood
s White blood cells (WBCs): These protect the
body from infection. Tests will check the amount
in your blood
s Hemoglobin (Hgb): This is a part of your red blood
cells that carries oxygen throughout your body. Low
levels of hemoglobin can cause anemia, which can
make you feel weak and tired. Tests will check the
amount in your blood
How can I manage PNH? 17
Know the full story.
At times, you may be feeling better, but your lab results
won’t show improvement. The reverse of this can also
happen. No one sign, symptom, or lab result defines
PNH. This is why it’s important to keep a close watch
on all three. It’s the best way for you and your doctor
to understand the full story of what’s going on with
your PNH.
Speaking with your doctor about
your lab results.
I see PNH
differently.
“I used to think hemoglobin
was all that mattered in PNH.
Now I check my LDH to see
what’s really going on.”
– Carlos*
To understand your lab results, you don’t need to learn
another language. Remember, your doctor is there to
help you. So don’t be afraid to ask questions!
Here are a few to help you get started:
“What does this lab test mean?”
“Are my results normal?”
“What does it mean if my results are above/
below normal?”
“Is there anything I can do to get them within a
normal range?”
Speaking openly can help you and your doctor better
manage your PNH.
18 How can I manage PNH?
Checkup: Quick facts about tracking your PNH.
s +NOWYOURLABRESULTSANDKEEPTRACKOFTHEM
s ,$(ISTHEMOSTIMPORTANTLABVALUEBECAUSEITMEASURESHEMOLYSISTHEUNDERLYING
cause of health problems in PNH
s 2EMEMBERNOONESIGNSYMPTOMORLABRESULTDEFINES0.(4RACKINGSYMPTOMSAS
well as lab results, is key to PNH success
s 3HAREANYCHANGESYOUNOTICEINYOURHEALTHWITHYOURDOCTOR
s $ONTBEAFRAIDTOASKQUESTIONS
*Fictitious patient and account. Adapted from real patient stories.
How can I manage PNH? 19
Change the way you see PNH.
Finding a treatment
that fits.
While PNH is serious, a
lot is known about the
disease, and treatments
are available. Speak with
your doctor to find one
that’s right for you.
And get the help you need along the way.
PNH can be a scary disease. But understanding how it works
in your body can help you see it differently. It is possible
to manage PNH. And, even though it’s rare, you don’t have
to do it alone. There are a number of people and resources
available to help you take control of your disease.
Your healthcare team
Together, you and your doctor and nurses can develop a
plan to treat your PNH and watch your progress. But your
healthcare team is not just a source of treatment—they’re
also a source of information. Feel free to ask them any
questions about PNH.
Your loved ones
PNH can take a lot out of you, so it’s important to lean on
friends and family for support. Be sure to let them know what
PNH is and how you’re feeling day to day. That way they’ll
know when they need to reach out to lend a helping hand.
20 How can I find help?
T R E A T M E N T
S U P P O R T
Available to people with
PNH and their caregivers.
Your PNH community
PNH is a rare disease, but that makes those who have
it that much closer. Connect with others with PNH to
help you learn about, cope with, and confront your
disease. There are a number of online resources you
can use to find support (see page 25).
Call with no obligation:
1.888.765.4747
Monday – Friday
8:30
AM
to 5
PM
OneSource™
How can I find help?
Sometimes you just need to talk to someone who
understands. Through OneSource, you can do just
that. With one phone call, you can reach an Alexion
Nurse Case Manager who can provide information and
helpful tools to help you manage your PNH. They can
connect you with other people who have the disease.
Ask questions. Find answers. And do something that
you may not be able to do with others: talk about
your disease.
How can I find help? 21
Helpful resources
Aplastic Anemia & MDS International Foundation
(AA & MDSIF)
A nonprofit resource for assistance, advocacy, and
support for patients living with AA, MDS, and PNH.
www.aamds.org
National Institutes of Health
Part of the U.S. Department of Health and Human
Services, and a trusted source of research.
www.nih.gov
National Organization for Rare Disorders (NORD)
Dedicated to helping people with rare disorders like PNH.
www.rarediseases.org
OneSourceTM
Alexion Nurse Case Managers can help answer
questions about PNH and provide personal support
for people living with PNH and their caregivers.
1.888.765.4747
PNH Research and Support Foundation
Helps raise funds for PNH research and may offer
limited financial support for PNH-related expenses.
www.pnhfoundation.org
PNH Source
Complete information about PNH and helpful tools to
manage your disease, all in one resource.
www.PNHSource.com
PNH Support Group
An online support group for people with PNH.
www.pnhdisease.org
22 How can I find help?
Checkup: Quick facts about living with PNH.
s )TSOKAYTOASKFORHELP3TARTWITHYOURDOCTOR/NE3OURCEANDTHOSECLOSESTTOYOU
to build a strong support team
s 4HEREAREANUMBEROFRESOURCESYOUCANUSEFORINFORMATIONADVICEANDSUPPORT
s /NE3OURCECANHELPANSWERQUESTIONSANDCONNECTYOUWITHOTHERSLIVINGWITH0.(
How can I find help? 23
Building a better future.
It starts with the right tools.
Actively managing your PNH can go a long way. Use
these tools to help you take control.
PNH Symptom Checkup Chart
Record your symptoms. And track your lab results,
including your LDH levels. This tool was designed to
help you and your doctor keep your PNH in check. Bring
it with you on every visit.
Lab Tracker
Track your lab results over time and see your progress.
Bring this tool with you to your doctor’s visits and
record your lab test dates and results.
24 Toolkit
Patient/Doctor Discussion Guide
To get all your questions answered, go to each doctor’s
visit prepared. Add your own questions to this list and
take note of your doctor’s answers so you will remember
them later and be able to discuss them with your loved
ones and family members.
Interactive Symptoms Viewer
Knowing how you’re feeling will help you and your doctor
keep better track of your PNH and the risks associated
with it. Register to use this tool online at
PNHSource.com/patients/helpful-resources.
Toolkit
Download and access these tools
at PNHSource.com/patients/
helpful-resources or order them
by calling OneSourceTM at
1.888.765.4747.
Toolkit
25
Glossary of terms
Acquired
An acquired disease is not contagious or inherited from a family member. It’s a disease that
you develop over time.
Anemia
A condition in which your body does not have enough hemoglobin (the part of your blood that
carries oxygen). With anemia, you may have fewer whole red blood cells. This may cause you to
feel weak and tired.
Aplastic anemia (AA)
“Aplastic” means that bone marrow can’t produce new blood cells properly. As a result,
patients with aplastic anemia have fewer red blood cells, white blood cells, and platelets.
PNH is often found along with aplastic anemia.
Blood clot
Blood clots form when parts of your body’s blood clump together. In a healthy body, this can
stop bleeding when you’re cut or injured. But in certain conditions, these clumps can block
blood flow in the veins and arteries, which can be dangerous. In PNH, a clot can happen at
any time and can cause serious health problems.
Bone marrow
The soft tissue inside your large bones. It works to create the cells in your blood: red blood
cells, white blood cells, and platelets.
Bone marrow failure disorder
A disorder that causes bone marrow to decrease or stop making blood cells. AA and MDS are
bone marrow failure disorders.
Clone size
The percentage of cells in your body affected by PNH.
Complete blood count (CBC)
A lab test that gives the amounts of different cells in your blood.
Enzyme
A type of protein that helps reactions/processes happen in the body.
Erectile dysfunction (ED)
A condition found in men that affects their ability to achieve an erection.
Hemoglobin (Hgb)
The reddish-brown material found inside red blood cells. It carries oxygen throughout your
body. When it gets outside of your cells, it is harmful and can lead to serious health problems.
26 Toolkit
Hemoglobinuria
Hemoglobin in the urine. About 25% of patients with PNH have it at diagnosis, but most will
experience it at some time. Because of the reddish-brown color of hemoglobin, it results in dark,
sometimes “cola-colored” urine.
Hemolysis
When red blood cells burst. Hemolysis is the main cause of the major health problems in PNH.
Lactate dehydrogenase (LDH)
An enzyme found in red blood cells, released during hemolysis. Testing for LDH can help show how
much hemolysis is happening in your body.
Myelodysplastic syndromes (MDS)
A condition in which there’s a problem with the way bone marrow makes blood cells. About 2% of
PNH patients also have MDS.
Paroxysmal nocturnal hemoglobinuria (PNH)
A disease where red blood cells are created without a protective protein. This causes them to
burst (a process called hemolysis) and can result in serious health problems. Signs and symptoms
include stomach pain, difficulty swallowing, anemia, shortness of breath, and tiredness. Lifethreatening complications from PNH include blood clots, kidney failure, and damage to organs.
Progressive
A progressive disease is one that gets worse over time.
Pulmonary hypertension
High blood pressure in the arteries that deliver blood to the lungs. This means that blood has a
hard time getting to the lungs, causing your heart to pump harder.
Red blood cells (RBCs)
A type of cell found in your blood that delivers oxygen and removes waste (carbon dioxide) in your
body. Red blood cells affected by PNH are attacked and destroyed because they are missing a
protective protein.
White blood cells (WBCs)
A type of cell found in your blood that helps your immune system fight disease and infection.
Toolkit
27
In PNH, what you CAN’T see can hurt
you the most.
PNH is a disease that happens in the blood but impacts your entire body. And even
though it’s always happening, your body may not always show signs or symptoms.
You CAN do something about it.
Even if you can’t see or feel it, it’s important to manage your PNH. With the right
tools and support, you can take control. Start by speaking with your doctor to find a
treatment plan that’s right for you.
© 2011, Alexion Pharmaceuticals, Inc. All rights reserved. SOL-1221