For MLK Day – On Giving Blood, and Maybe Being the Match

January is National Blood Donor Month. For those who can give, it’s never too late; the need is year-round.

A few years back, I wrote on the value of donating blood, as many will do today to honor the birthday of Dr. Martin Luther King, Jr. When I was practicing hematology I wasn’t aware of this practice, which now seems integrated with nationwide MLK National Day of Service events. The Orlando Sentinel published an article linking blood donation with MLK on January 14 1988.

Here are some resources for people who’d like to know more about giving blood:

Give Your Blood To Save a Life, Poster (American National Red Cross), U.S. National Archives

Give Your Blood To Save a Life, Poster (American National Red Cross), U.S. National Archives

The American Red Cross provides information on when and where to donate blood, as well as helpful instruction on the process of giving for first-time donors.

The AABB, formerly the American Association of Blood Banks, covers transfusions and related therapies.

America’s Blood Centers – a large network of non-profit community blood centers.

The New York Blood Center – a terrific local resource for my neighbors, a pioneer in blood banking and resources for patients worldwide.

For those who’d consider bone marrow donation, the National Marrow Donor Program helps patients with leukemia and other conditions find matching bone marrow donors.  The agency provides, also, financial assistance to some who can’t afford needed transplants.

Today, I learned that Robin Roberts, the GMA anchor who has been through breast cancer treatment and, subsequently, a bone marrow transplant for a rare blood disorder (MDS), has launched a public service campaign to encourage blood and marrow donors. Each of us can only do what we can. That she is alive and putting her name behind the drive, telling her audience what they can might to do to aid others, is heartening.

As someone who has benefited from the generosity of healthy donors, and the kindness of strangers among those, thank you!

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Blood and Hip Surgery: New Study Supports Fewer Transfusions

Under the radar, over the holiday week, the NEJM published a report on transfusion requirements in older adults who surgical hip repair. The main finding is that most patients, including the elderly and those at risk for cardiac complications of the procedure, don’t benefit from getting so many red blood cell transfusions as is commonly prescribed.

The study, funded by the NHLBI, involved more than 2000 adults over 50 years of age who underwent hip surgery. Overall the patients were quite elderly, with a mean age above 80 in each group. The trial included patients with heart disease and risk factors for cardiac complications. Participants were randomized to receive red blood cells if their hemoglobin fell to a level below one of either two thresholds: 10 or 8 gm/dl. What happened is that, at the time of discharge from the hospital and by 60 days after the procedure, the rates of death, coronary syndrome and other complications were the same.

An accompanying editorial weighs in on the study and conclusion, that a standard threshold for ordering transfusions in the context of major hip surgery might be lowered. Reducing transfusions would lower demands on the blood supply, lessen the costs of administering these infusions, and reduce complications from infected or otherwise-damaging pints.

The study is important because it bolsters the evidence that too many units of blood are administered routinely.  Sometimes with good reason, busy surgeons recommend a threshold for what’s almost an automatic order that blood to be given. If there is such a threshold in a SICU (surgical ICU), operating room or elsewhere, this report suggests it’s often too high.

It would be better, for sure, if transfusions were ordered on a case-by-case basis, with input by a doctor who would assess each patient’s baseline level of hemoglobin and other relevant factors. For example, a patient who’s been anemic for years may tolerate a lower hemoglobin level than someone who’s never been anemic before, or whose lung function is marginal.

Still, the main take is that many patients undergoing surgery need less blood than their doctors realize, and that we can safely, overall, reduce the number of transfusions ordered for many patients, even in those who are older and with risk of heart disease.

What patients might do: if you’re going to have major surgery, talk with your doctor about whether you might need blood and how the surgeon will decide if you need blood or not, and how much. If you have a strong preference to avoid transfusion, let your doctor know about that and discuss how you might avoid getting unnecessary pints.

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Gregg Allman Stars in Hepatitis C Awareness Campaign, with Merck

This weekend I learned that Gregg Allman, of the Allman Brothers, has hepatitis C. Not just that; he underwent a liver transplant last year for treatment of liver cancer. This information came my way via CNN, in a clip narrated by Dr. Sanjay Gupta. The cable TV crew filmed the old rocker in Macon, Georgia, at the band’s Big House.

Gregg Allman, performing in 2010 (Wikimedia Commons)

“He’s taping a public service announcement for the drug company Merck, about hepatitis C,” Gupta says 40 seconds or so into the clip (italics added, ES).

Hepatitis C stays silent in many carriers, meaning that most people with the virus are unaware of their infected state. The liver-infecting virus spreads most often by contaminated needles, sexual relations or transfusion of infected blood. Over time, the virus tends to cause liver damage and blood problems including anemia and, rarely, a condition called mixed cryoglobulinemia. In patients with long-standing hepatitis C, there’s a significantly elevated risk of developing liver cancer.

For two decades there have been a few, fairly effective anti-viral drugs available for hepatitis C. Treatment generally reduces patients’ anemia and liver disease, which leads them to feel better, and also reduces the risk of the long-term effects of infection, including liver cancer. Last month the FDA approved two new drugs for hep C: Victrelis (boceprevir), manufactured by Merck, and Incivek (telaprevir), by Vertex Pharmaceuticals.

While I have no formed opinion as to which of these new drugs is most effective or less toxic or more affordable in the long term for patients with hepatitis C, I do find it strange that Gregg Allman will be singing for Merck.

Eat a Peach (album cover)

The ethics of this are complicated: On the one hand, it might be a good thing for a music icon to raise public awareness about hepatitis C, so that more people at risk might get tested and then treated early before they develop severe liver disease and cancer, and would feel better. Gregg Allman is in a position to spread that message effectively: “If I have hep C, you might have hep C. Let me tell you about it…” (somewhat in the style of Magic Johnson, on HIV).

On the other hand, the notion of a post-transplant musician serving as the public’s primary source for information on hepatitis C seems preposterous, especially if he’s tied in with a pharmaceutical company with a stake in the matter. The situation is reminiscent of Sally Fields starring in commercials for Boniva, an osteoporosis drug.

You might ask yourself – and it’s not a trivial exercise – who can best, and objectively, inform the public about viral liver infections and the potential benefits of treatment: doctors? (we harbor biases; many have industry ties); patient peers? (Allman is a heightened example, but he’s hardly objective about this, either); newspapers? (or radio…

Will Allman’s be wasted words? (Hard to resist.) Really I’m not sure.

But I might go to Allman’s concert for the American Liver Foundation, at the Beacon Theater, scheduled for July 27.

All for now.




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Dr. Greenfield is Human

A few days ago I read that Dr. Lazar Greenfield, Professor Emeritus at the University of Michigan, resigned as the president-elect of the American College of Surgeons over flak for authoring a Valentine’s Day-pegged, tacky, tasteless and sexist piece in Surgery News. The February issue is mysteriously absent in the pdf-ied archives. According to the Times coverage: “The editorial cited research that found that female college students who had had unprotected sex were less depressed than those whose partners used condoms.

From Pauline Chen, also in the Times:

It begins with a reference to the mating behaviors of fruit flies, then goes on to discuss studies on the menstrual cycles of heterosexual and lesbian women who live together. Citing the research of evolutionary psychologists at the State University of New York, it describes how female college students who had been exposed to semen were less depressed than their peers who had not, concluding: “So there’s a deeper bond between men and women than St. Valentine would have suspected, and now we know there’s a better gift for that day than chocolates.”

Not that I’m OK with any of this, as I’ve known the ickiness of older male physicians who don’t even realize when they’re being inappropriate.

But this morning I learned from Orac that Dr. Greenfield is the Dr. Greenfield, the one that invented the Greenfield filter. This threw me a bit, because I admire Dr. Greenfield for his work. He’s saved a lot of lives, perhaps tens of thousands. (I’m guessing on this number; it could be more, the point is – a Tsunami’s worth of lives.)

Doctors, including non-surgeons like me, would sometimes advise insertion of Greenfield filters in patients with blood clots and a contraindication to blood thinning. One example of countless I recall in my own experience as an oncologist: an elderly patient with pancreatic cancer and limited mobility who had a DVT in the leg and a brain met. We wouldn’t want to give the patient a standard blood thinner, like heparin or coumadin, because the tumor in the brain might bleed with catastrophic effect.

The common teaching was that a Greenfield filter, inserted through a large thigh vein up to the inferior vena cava, would prevent a blood clot from spreading from a patient’s leg up to the heart’s right chamber and into the lung’s circulation, where it might lodge in the form of a pulmonary embolus, a serious and sometimes lethal condition.

As a patient, I once had a newer-model Greenfield placed on a temporary basis. Because I’d had a major DVT while immobilized after spine surgery for scoliosis as a teenager, and then I had breast cancer – another risk factor for DVT – when I needed spinal repair as an adult in 2003, my orthopedist and hematologist were concerned that my risk for developing another major clot was great. Because they couldn’t put me on an anticoagulant for days after such a big operation, they advised prophylactic insertion of a temporary Greenfield device. I accepted the plan, hesitatingly, as reasonable.

So from both my professional doctor’s and my patient’s perspective, I’ve perceived value in Dr. Greenfield’s contribution and possibly benefited from his work. Then again, a 2000 review in Blood suggests more evidence is needed to support the filters’ widespread use. I agree.

The clearest take, maybe, is that some powerfully driven, innovative and brilliant people make personal mistakes.

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Thoughts on Geraldine Ferraro, and Myeloma

Like many New Yorkers, feminists?, hematologists and other people, I was saddened to learn yesterday of Geraldine Ferraro‘s death. The Depression-era born mother, attorney, criminal prosecutor, Congresswoman, 1984 Democratic VP-candidate and part-time neighbor to yours truly, succumbed to complications of multiple myeloma at the age of 75.

Abnormal plasma cells in a bone marrow sample said to be from a patient with myeloma (Wikimedia Commons). Plasma cells have nearly-round, eccentric nuclei and abundant cytoplasm (ES).

Myeloma is a cancer of plasma cells – specialized white blood cells (mature B lymphocytes) that make antibodies. Plasma cells normally develop in the bone marrow; they can exit into the bloodstream, which is why this condition is often called a tumor of the bone marrow or, occasionally, sometimes, as a leukemia. The term myeloma comes from Greek roots – muelo (which can refer to the bone marrow) and –oma, which in medical parlance has come to stand for a tumor and may derive from soma (body).

According to the NCI, over 20,000 North Americans receive a myeloma diagnosis, and approximately 10,000 die from the disorder each year. It tends to arise in older folks, and is slightly more prevalent in men than in women. According to the SEER data, in 2007 there were over 61,000 men and women in the U.S. alive with a history of this disease.

What’s notable to me, as a hematologist, about the former congresswoman is that she lived with myeloma for over 12 years: She survived with a disease for which there were few treatments available when she was on the Presidential ticket. This was partly due to luck – always a factor in cancer outcomes, as some cases are intrinsically more aggressive than others; partly due to her access to excellent doctors and good care; and, also, likely due to advances in myeloma treatment over the past two decades.

Some perspective: When I completed my fellowship in 1993, the median survival for someone with myeloma was less than 3 years. Starting around then, most specialists steered patients under the age of 65, and in some communities, older patients as well, toward autologous stem cell transplantation – an aggressive approach that’s been shown to prolong lives of patients in randomized studies. (For the record, I’ve never been convinced by those data.) More recently, old drugs like thalidomide and its fresher derivative, lenalidomide (Revlimid), along with new drugs like bortezomib (Velcade) have demonstrated efficacy in this disease.

In my opinion, what’s ahead for doctors caring for myeloma patients – and for the patients, even more so – in this next decade, is to see if these old and new pills might be better, less costly and less toxic than transplant-based treatment regimens.

A final thought on Ferraro’s care, is that it seems she benefited from the care of experts: hematologist-oncologists, transplant physicians and other specialists and subspecialists. With all the push now for more primary care doctors – who are indeed needed – her survival with what might have been a quickly terminal illness is a testament to the value of knowledgeable, well-trained physicians who keep up with developments in an evolving field.

As for the ceiling-breaking congresswoman, my thoughts are with her family now. She was a remarkable lady in many ways.

(all links accessed 3/27/11)

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Tennis News and Why a Healthy Young Woman Might Get a Pulmonary Embolism

Yesterday I learned that Serena Williams, the tennis pro, has been treated for a pulmonary embolus. My husband found out this morning upon reading the newspaper. He wondered why this would happen to a strong, young, athletic woman.

Without delving into the private or specific aspects of her case:

A pulmonary embolism, or PE in doctor-speak, happens when a blood clot enters or forms in the blood supply to the lungs. It’s a serious condition, because when blood vessels in the lungs are compromised, the lung cells can’t deliver fresh oxygen to hemoglobin that would normally pass through in red blood cells. Symptoms sometimes but not always include shortness of breath, pain in the chest that’s sharp in quality, and fatigue. Usually the diagnosis is made by a scan, such as a VQ or a special kind of (spiral) CT.

tennis racket and ball (Wikimedia Commons)

Treatment includes a blood-thinner, usually for a period of months. At first, and depending on the severity of the circumstances, patients may benefit from oxygen treatment through a light face mask or by nasal prongs. In general, doctors monitor patients for a short time in a hospital, to make sure the clot doesn’t get worse and that they don’t need additional oxygen support, and that the anti-coagulant is working.

When patients get blood clots it’s usually because they have a genetic tendency combined with some situation that aggravates that disposition. For example, if someone is born with a deficiency in a protein – of which there are quite a few – that normally dissolves clots, they might feel fine throughout life and be unaware of their hypercoaguable state. But after a big surgery, or if they were immobilized and dehydrated on a long plane ride, that might lead to a clot formation.

Sometimes surgery or inflammation in an extremity, such as a leg, can dispose to clot formation. When a clot forms there, it’s called a deep venous thrombosis (DVT) and that can, especially if untreated, break off and move through the large veins, to the right side of the heart, and then enter the pulmonary artery and smaller vessel or vessels in the lung. In that case it’s a PE.

Pregnancy, in itself and especially in women with underlying clotting disorders, can dispose young women to a DVT or PE. The same is true for estrogen-containing medications including birth control. Smoking, too –

A short personal perspective is that I once cared for a woman who had a PE who was young and attractive. She had been on a long, international flight a few days before she came to the E.R. It took hours for her to get past triage, and I suspect that was because she looked so healthy. It turned out she had a huge clot in her lungs, and a complex clotting disorder.

If a person with a DVT or PE turns out to have a genetic disposition, it doesn’t mean they need life-long treatment with a blood thinner. Depending on the location, severity of the clot and the circumstances, treatment is given for weeks or months. But it can be helpful to know if you have a clotting disorder. Some patients take prophylactic, low-doses of blood thinners when they travel or after immobilizing surgery, like a hip replacement.

Here are some useful websites that provide information on blood clots:

The American Society of Hematology (which confirms that March is DVT Awareness Month)


Medline Plus

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On the Importance of Giving Blood

The other day I wrote on advances in artificial red blood cells and developing platelets from stem cells. But those methods are in early research phases. Meanwhile, many patients need blood donated by adult humans, now.

I have personally benefited from the generosity of blood donors. Some were strangers: In 1974 I received seven units during and after surgery. I cannot thank those kind people directly, because I don’t know who they are, but I am surely grateful, besides forever fortunate that those units didn’t harbor hepatitis or other now-known viruses. In 2003, friends and acquaintances – a college friend’s wife, who over time has become as a cousin; a generous and strong physical therapist who worked with me then, whom I’ve never thanked sufficiently, among others; and family – stepped in and helped me get through another tough procedure by offering those vital pints.

If you’re healthy and without anemia, please consider donating blood through one of these agencies:

The American Red Cross

America’s Blood Centers

New York Blood Center

Thank you,


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Notes On a New Kind of Anticoagulant

On the hematology front –

Last weekend at the annual meeting of the American Society of Hematology (ASH), researchers presented data on a new kind of blood thinner. Rivaroxaban (Xarelto) is a pill that works by blocking the activated form of human clotting factor X (Xa). The NEJM published the EINSTEIN* findings on-line ahead of print, coincident with the presentation.

The research includes two reported trials. In the first, an open-label randomized study of 3449 patients with acute deep venous thrombosis (DVT), subjects received either rivaroxaban pills or a standard treatment regimen starting with an injected blood thinner (enoxaparin) followed by an oral Vitamin K antagonist, like coumadin.  The main findings in this Acute DVT Study was that the new drug, rivaroxaban, is as good (“non-inferior”) in terms of preventing recurrent clot as is the older regimen and bears a similar safety profile.

The second, parallel EINSTEIN-extension trial involved randomization of 1197 patients after treatment for acute DVT to take oral rivaroxaban or a placebo for an additional 6-12 month period. In this study, patients taking the experimental anticoagulant had fewer blood clots than those on placebo. Unsurprisingly, there was a slightly increased reported incidence of major bleeding (4 patients, 0.7%) in patients on the blood thinner relative to placebo (0 patients, 0%). This difference was not statistically significant.

Both trials were funded by Bayer Schering Parma and Ortho-McNeil. According to a Bayer press release of last August: “If approved by the FDA, Ortho-McNeil, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. (a Johnson & Johnson Company), will commercialize rivaroxaban in the U.S.”

What’s good, clearly, is that several effective anticoagulants are emerging as alternatives to heparin, which must be injected, and coumadin. In October the FDA approved the first of these drugs, dabigatran (Pradaxa), for prevention of stroke in patients with atrial fibrillation. This was big news in cardiology circles, with reason. Another area of use for these agents would be in prophylaxis for DVT in patients who undergo hip replacement and some other kinds of major surgery.

In my experience as a hematologist, and as a patient who’s had a DVT, I know that coumadin dosing is not straightforward. Because the therapeutic dose varies so much among individuals in ways that depend on genetic factors and potentially change over time with diet, patients need provide initially frequent and then periodic blood samples. The repeated blood tests don’t require large amounts of blood, but they’re annoying and costly. What’s more, the hassle – pain of blood draws, driving or walking to a clinic for sample taking, waiting for results – interferes with quality of life.

Giving intravenous blood thinners is not convenient either, as these need carefully-monitored infusion of the drug, and it’s easy to overshoot or undershoot the dose. Injectable blood thinners like low molecular weight heparin are easier to dose than conventional heparin, but still it’s pretty unpleasant for a patient to have to inject herself once or twice a day with a needle.

Soon we’ll see what the FDA says about rivaroxaban. I’m not excited about this one agent as opposed to any other, but I am enthusiastic about this new class of drugs. These should benefit people whose medical conditions warrant the use of blood thinners.

*The “EINSTEIN” investigators are based in the Netherlands and are listed in the original paper. It’s hard to find an explanation of the acronym.

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Considering Evidence for a New Drug for Immune Thrombocytopenia Purpura

I’ve been wondering, lately, why so many of the medical blogs cover the same topics, like last week’s lung cancer detection trial, which are often the exact same studies as are reported by conventional news outlets. I’ve been trying, here, to sometimes consider new published articles that seem important to me but, for whatever reasons, don’t get so much attention.

Here’s one:

Yesterday’s NEJM includes an article Romiplostim or Standard of Care in Patients with Immune Thrombocytopenia.* It’s about a drug, manufactured and sold by Amgen as NPlate, that received FDA approval for treatment of chronic immune thrombocytopenia purpura (ITP) in August, 2008. Some consider ITP a rare disease, and I suppose it is; my perception is skewed by the fact that as a practicing hematologist I saw patients with ITP almost constantly in the clinic and hospital. In patients with this autoimmune condition, the body produces pathologic antibodies that bind and lead the tiny, clot-forming blood cells to destruction. Sometimes patients with chronic ITP need treatment, such as steroids, surgical removal of the spleen (splenectomy) or other drugs that raise the platelet count and reduce their risk of bleeding.

The new-ish drug, romiplostim, is effective in raising the platelet count in most patients who are said to have chronic ITP. It’s similar to another platelet-stimulating agent, eltrombopag, that’s manufactured and sold by GlaxoSmithKline under the brand name Promacta. Eltrombopag received FDA approval for the same condition in November, 2008.

So long before reading the thoughtful editorial* by Dr. James George, this hematologist was impressed by the availability of two agents that work by stimulating platelet production in the bone marrow. Dr. George considers the possibility that these new drugs alter the usual but debatable algorithms that most hematologists use in caring for patients for ITP. He acknowledges having consulted to the study’s sponsor, Amgen, on this drug and serving as an investigator in clinical trials, and considers:

…In this randomized study, 85 investigational sites in 14 countries enrolled 234 patients…The conclusions are clear. The outcomes were better in patients receiving romiplostim than in patients receiving standard care (short of splenectomy): romiplostim was associated with a greater incidence of a sustained platelet response, less bleeding and fewer transfusions, a decreased requirement for other treatments (including splenectomy), and greater improvement in quality of life. The side effects of romiplostim therapy were minimal, but …confidence about the safety of the drug requires that more patients be observed for a longer time. Because patients treated with romiplostim had better outcomes, does the work of Kuter and colleagues establish romiplostim as the new standard of care?

As I read the original study results, this issue – of possibly changing the standard of care in this disease – became evident. His question is on-point.

The problem is this: In the study, the authors treat a total of 234 patients who are said to have chronic ITP. But, if you look closely at the eligibility for enrollment, besides having a low platelet count (defined for the study as less than 50,000 platelets per microliter of blood, which in itself is a questionable criterion), examination of a bone marrow-biopsy specimen was required to confirm the diagnosis of immune thrombocytopenia in patients older than 60 years. According to Table 1 in the paper, the median age for study participants was 57 years. This means that more than half of the participants were under 60 years and, as far as we know, they did not have a diagnostic pathology test for ITP. They might instead have a myelodysplastic syndrome or other bone marrow disorder that was missed.

Why this matters, besides to patients who have low platelets and their hematologists, is that it’s really a problem in the practice of evidence-based medicine. If data are derived and published from fundamentally flawed studies, in which the patient groups who respond or don’t to a particular intervention are not well-defined by careful diagnostic parameters, the conclusions we draw from those studies may be incorrect.

I am definitely in favor of evidence based medicine, but we need to be careful in how we evaluate the results of published studies, even in the best of journals, and how we incorporate those findings into recommendations for care.


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Noting the Death of Jill Clayburgh Who Lived For 21 Years With a Chronic Form of Leukemia

I was saddened yesterday to learn of the death of Jill Clayburgh. The 66 year old actress died on Friday in her Connecticut home. According to ABC news and the LA Times among other reports, she’d had chronic lymphocytic leukemia (CLL) for 21 years. This means she lived with CLL for nearly a third of her life.

It happens that I used to spend much of my time thinking about CLL; it was the focus of my laboratory’s research program, and I cared for many patients with this particular form of leukemia.

It’s an instructive disease at several levels:

Chronic lymphocytic leukemia is the most common form of leukemia in adults in Europe and North America. The National Cancer Institute reports that there are approximately 15,000 new cases each year in the U.S. Although CLL is not curable, it is an indolent type of tumor, a slow-growing cancer a person might live with for years and even decades. For this reason, it is perhaps the best example of a malignancy for which a “watch and wait” approach is often, but not always, appropriate.

By now, in 2010, it seems the public has a good sense that the big C, i.e. “cancer” is not one disease, but many. For leukemia it’s the same deal: there are at least several dozen forms, perhaps over a hundred identified by now. The nomenclature can be confusing to people who receive a new diagnosis and to doctors, as well, who many not be up-to-date on new molecular classification schemes.

The image to the left, from Wikimedia Commons, reveals a high-power magnification (1000 X) of a Wright’s stained peripheral blood smear from a patient with CLL. The lymphocytes, with the darkly staining nuclei and scant cytoplasm, are CLL cells.

A helpful framework, I find, for understanding leukemia is to think, first, in terms of what kind of cell has become malignant in each case – what an oncologist would call the cell of origin for the tumor. Leukemia is, by definition (from the Greek roots leuk, for white, and haima, of blood) an excess of white cells in the blood. But there are multiple kinds of white blood cells, and each type can form one or more type of leukemia. The most basic leukemia categories are three: tumors of myeloid cells, such as neutrophils and their precursors; tumors of lymphocytes, such as T or B cells; and tumors of other white blood cells that are less common in the circulation. CLL is a tumor of B-lymphocytes, the kind of white blood cells that normally mature to form antibodies.

A second way of classifying leukemia is based on the rapidity of tumor cell growth. In CLL, the malignant B cells tend to divide slowly, rendering this a chronic, i.e. indolent disease in most cases. Now, the disease might be detected in its earliest phases upon routine blood testing, sometimes years before it would become clinically apparent by causing symptoms like uncomfortably swollen glands or fatigue from anemia.

Here are some websites that provide open-access information about CLL:

American Cancer Society

Cancer.net (ASCO)

Leukemia & Lymphoma Society


National Cancer Institute


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