Pic Of The Day

Posted by rob on December 20, 2004 under Uncategorized | Be the First to Comment

A woman walks through the fresh snow, near a tree, under a cloudy sky in Saint-Georges, in the Jura region of the Canton of Vaud, Switzerland. Overnight Saturday wind with speeds up to 105 miles per hour have been measured and snow has fallen in some lower areas along the alps of Switzerland.

Pic Of The Day

Posted by rob on December 19, 2004 under Uncategorized | Read the First Comment

Christmas lights are seen on a home in the Bay Ridge section of the borough of Brooklyn in New York, December 18, 2004. Homes in this neighborhood are especially festive every year, with families adding to their annual displays in friendly competition.

In search of the sugar-coating

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In search of the sugar-coating
The new product patents regime will decide the future of hundreds of leukemia patients
Posted online: Sunday, December 19, 2004 at 0000 hours IST

â??â??Iâ??VE lost everything trying to battle this illness,â??â?? shudders P Sundaram (name changed), resting in his cramped two-room home in Bhandup, a Mumbai suburb. The 59-year-old was devastated when he was diagnosed with Chronic Myeloid Leukemia (CML), a cancer of the white blood cells, back in 2002. His condition has improved, he says, after a yearâ??s treatment with a locally manufactured drug.

Doctors agree. Though they admit they cannot predict the long-term impact of the drug, they have told Sundaram it is fighting the cancer better than anything else he has taken.

The generic drug regimen costs Sundaram Rs 10,000 per month. Itâ??s a considerable sum for the ailing man, and the former businessman doesnâ??t even want to think about the fallout of the Patent Act amendments.

While doomsayers are unlikely to be proved right in their prediction that generic drugs will disappear altogether come January 1, 2005, theoretically, the only option for Sundaram and others like him â?? the estimated prevalence of CML in India is 15,000 patients every year â?? would be the imported brand Gleevec (Glivec in India), produced by Swiss pharma major Novartis.

Introduced in India in 2002, the cost of the drug is Rs 1,20,000 per month.

TO protest against law amendments that will bar local drug companies from manufacturing patented products through a different process, Mumbai-based NGO Cancer Patientsâ?? Aid Association (CPAA) filed a writ petition in the Supreme Court in September 2004. The petitioners challenged Novartisâ?? exclusive marketing rights (EMR) for Gleevec.

Novartisâ?? EMR, acquired in November 2003, prevents competitors from duplicating and selling the same compound â?? Imanitab Meyslate â?? under other brand names and at cheaper prices for five years. In essence, it means the pharma major has a monopoly over Gleevec.

â??â??Itâ??s illegal for Novartis to ask for exclusive rights, since Imanitib is a pre-1995 molecule. For patients who cannot afford their prices, local drugs are the only way to prolong life,â??â?? says Dr Purvish Parikh, professor and head, medical oncology, Tata Memorial Hospital, Mumbai.

Prior to the EMR, nine Indian companies were making this drug. Six of them â?? Ranbaxy, Cipla, Sun Pharma, Camlin, Emicure and Intas â?? have been barred from further production by the Madras High Court, while Shanta Biotech and NATCO are among the three still producing the generic drugs.

The CPAA petition says that the absence of low-cost versions of the drug would mean denial of the right to life enshrined in Article 21 of the Constitution. The association has also sought government price control over life-saving drugs.

But Novartis is not open to price controls. â??â??Since 3,000 patients receive the drug free, we see no reason for price control,â??â?? says a company spokesperson.

WATCHING the unfolding patent drama closely are the 3,000 patients on the Glivec International Patient Assistance Program (GIPAP). Novartisâ?? altruistic initiative is a rare effort in the pharma industry.

Chosen on the basis of medical and economic criteria, the beneficiaries include Laxman Waskar, a leukemia patient. â??â??The tablets are miracles. I feel much better after taking them,â??â?? says the 29-year-old screen-printer. The six-pills-a-day he receives under GIPAP are a part of routine now. His blood count is better, his spleen is no longer enlarged, and he has more energy.

BUT questions are being raised about the term of this scheme. â??â??Will they support these patients throughout their lives? And what about the many others who are in as dire need?â??â?? asks Y K Sapru, founder-chairman of CPAA.

Quizzed on the future of the free drug scheme, the Novartis spokesperson would only say, â??â??Following the launch of the generic Imanitab, the GIPAP was modified between May and December 2003. Newly diagnosed patients were asked to avail of generic manufacturersâ?? assistance programmes.â??â??

http://www.indianexpress.com/full_story.php?content_id=61095&spf=true

Preview: Healing Music, Sustaining Love: Mother with leukemia and daughter play through pain

Posted by rob on December 18, 2004 under Uncategorized | 2 Comments to Read

December 18, 2004

By Paul Denison 
The Register-Guard
  

 

 

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Anyone who sees Misty River in concert might notice something special going on between two of the four women in this popular Northwest folk group: the older woman who plays guitar and the petite bass player who is young enough to be her daughter.

That’s because Carol Harley, 55, and Laura Quigley, 28, are mother and daughter. It’s also because they’ve been through a lot together.

Laura was just a toddler 26 years ago when her mother survived melanoma that was supposed to kill her.

She was not yet a teenager when an out-of-control downhill skier at Mount Bachelor swerved to avoid her and slammed into her mother instead, crushing her spine. The pain was so intense, even with painkillers, that Harley had to give up her job as a teacher at River Road Elementary School.

Four years later, while still in high school, Laura was a 24/7 home caregiver for an entire summer as her mother painfully recuperated from surgery to fuse several vertebrae in her back.

And now, she’s at her mother’s side, on the road and on stage, as they confront the third major medical crisis of their lives: chronic myelogenous leukemia, or CML.

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mother and daughter

Carol Harley (right) has had to lean on daughter and band mate Laura Quigley as she goes on playing in their band, Misty River, while being treated for leukemia. “The ante’s been upped a little on this one,” Quigley says of her mother’s illness.

Photo: Brian Davies / The Register-Guard

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“The ante’s been upped a little on this one,” Quigley says of her mother’s illness. “It scares me pretty good.”

Harley got the diagnosis in March of this year. The band was then recording its third album, “Willow,” and had just been selected to represent Americana music at the Shanghai International Music Festival in China.

The go or no-go decision was pretty much up to Harley. “I knew I wanted to go,” she says. She got her doctors’ blessings and agreed to start oral chemotherapy before she left, with the understanding that she could stop if the medicine made her sick (which it did).

Unable to sit because of her chronic back pain, Harley bought three economy-class seats for less than a single first-class or business-class ticket for the China trip so she could lie down.

“It was awesome,” she says. “I slept all the way over and all the way back.”

In Shanghai, where Misty River performed briefly three times a day for seven days, she enjoyed evenings out in a wheelchair, pushed by one of the others, with orthopedic pads to help take the pressure off her lower back.

“The entire experience was just fabulous,” she says. “The Chinese people are wonderful.”

Back in Oregon, Misty River released “Willow” and promptly went on a Northwest tour to promote the album. After that, they went back into the studio and recorded “Midwinter,” a Christmas album, which their fans had been requesting for years. Now they’re on tour to promote that album.

Starting with an appearance on Oregon Public Broadcasting, the group did 11 performances in a row before taking a brief break earlier this week. The band performed in Corvallis on Friday, will do two shows in Florence today and will do two more Sunday in the Hult Center’s Soreng Theatre.

On Monday, they will perform for residents of Spring Valley Assisted Living in Springfield and then climb back into their minivan for a trip to Madras and yet another concert.

This is a tough schedule for any band, but even more so for Harley. She has to ride in a reclining position and has to be helped into and out of the van (into a recliner they carry with them) and on and off stage. It’s also demanding for Quigley, accordionist Dana Abel of Eugene and fiddler Chris Kokesh of Portland, who do all of the driving, lifting and other physical work of touring.

“I get so much help from these hard-working, talented, intelligent young women I’m with,” Harley says. “I’m just astounded as to the help I have. It gives me a lot of energy. Misty River has been a great therapy for me. I’m lucky.”

She also gets support from Misty River fans.

Harley can’t afford a bone marrow transplant, the only cure for her type of leukemia, because Medicare doesn’t cover it. She’s now in a one-year clinical trial at Oregon Health & Science University in Portland. The program pays for the relatively new “miracle drug” Gleevec but not for Interferon, an older medicine that’s also part of her treatment. She has no prescription coverage.

The Interferon initially cost about $1,000 a month out of pocket, she says, but she’s now taking a lower dose and her costs have dropped to $300 or $400 a month. When the clinical trial ends next May, she will have to find about $8,000 a month to pay for Gleevec.

“I get overwhelmed about that,” she says. “You get wiped out pretty quickly.”

Abel, who serves as Misty River’s de facto CEO, says she would like to “go public” with Harley’s story as an example of how people can fall between the cracks in today’s health insurance system.

Misty River at first decided not to make a fuss about Harley’s illness. “We didn’t want our fans to get depressed about this,” Abel says. “We didn’t want them to come to our shows and feel sad.”

But now the band puts out a can at each show to collect contributions to the Carol Harley Leukemia Treatment Fund.

“We get several hundred dollars a show,” she says. The fund is now up to more than $20,000. Others in the Northwest music community are organizing 2005 benefit shows for the fund, including one set for April 9 at the Shedd Concert Hall.

Harley says she draws strength and energy from the audience reaction to Misty River’s music and group chemistry. Although she has to take a painkiller before each concert, she believes that on-stage adrenalin rush stimulates the production of endorfins, which are natural painkillers. And she says she knows that sound waves are healing, especially the “big, booming upright bass” played by her daughter.

“Sometimes I’ll be in the middle of a song or a banjo song, and I’ll feel like hurling,” Harley says. “My daughter knows when this is happening, and she just comes out of her body and hugs me and says, `Keep going mom, you can do it.’ ”

If the time ever comes when she does have to leave the stage to throw up, Harley says, her daughter intends to tell the audience that the truth has finally come out: “My mother is allergic to the banjo.”

Quigley says she has “always been my mom’s companion in life and survival,” through two divorces, health crises, starting and building a band. She says she relates to her mother on many levels: as daughter, co-worker, de facto sibling, adult companion, even tenant (she rents a Portland house from Harley). And definitely as a caregiver.

For more than a year before Harley was diagnosed with CML, both women sensed that something was seriously wrong.

“I could feel it deep inside me, at a deep cellular level,” Harley says, “and it was.” When her mother broke the news, Quigley says, “I just said `Aha,’ and asked her to tell me the name of it again. Then I sat down, held her arms and told her this was no big deal: `You’re the same, I’m the same, and we can deal with this.’ ”

But it’s not always easy, for either of them.

After a show one night, Quigley was guiding her adrenalized and neurologically wobbly mother offstage through a mess of cords on the floor when her heel caught on one of them and she couldn’t free herself.

“She had a miniature meltdown,” Quigley says. “She said, `My shoe is stuck! I’m such a mess! I’m a total mess! I’m so sorry!’ She almost totally lost it. She was mad about that shoe. I was steady as a rock. She took a deep breath, put her stage face on and did a 180. `OK. I’m ready for the encore.’ All this took only a few seconds. It was extremely dynamic of her to be able to oscillate that far. I said to myself, `Go, mom! That’s an incredible display.’

“My mom’s incredible. She’s absolutely incredible. She’s really strong, and she’s really dedicated to her fans.”

Quigley admits to being irritated with her mother sometimes – “Why does she have to freak out?” – and to being fearful about her long-range prospects.

“I’m holding it at bay,” she says. “It is what it is. If I think of it too much, I often get a little scared about the span-of-life thing.”

Having related to her mom in so many different ways in varying circumstances over the years, Quigley wishes they had more time now to be just mother and daughter.

“We kind of fit it in now and then,” she says.

PREVIEW

Misty River CD release concerts for “Midwinter – Songs of Christmas”

When and where: 2 p.m. and 7 p.m. today at North Fork Grange, North Fork Siuslaw Road, Florence; 2 p.m. and 7 p.m. Sunday (with guitarist Doug Smith and the Oregon Junior Girlchoir) in the Soreng Theatre, Hult Center, Seventh Avenue and Willamette Street, Eugene

How much: $12 general admission in Florence; $12 and $16 in Eugene

Tickets: For the Florence show, Old Town Books or at the door; for Eugene, 682-5000 or www.hult center.org

Pic Of The Day

Posted by rob on under Uncategorized | Read the First Comment

In this image released by NASA on Thursday, Dec. 16, 2004, a sidelong glance at Saturn and its magnificent rings is shown as Cassini pierced Saturn’s ring plane

Pic Of The Day

Posted by rob on December 17, 2004 under Uncategorized | Be the First to Comment

This handout picture from the US Coast Guard shows lenticular clouds hovering over Mount Erebus volcano in McMurdo Sound where massive icebergs from the Ross Ice Shelf are clogging the sea.

Re-analysis of the cell line NALM-1 karyotype by GTG-banding, spectral karyotyping, and whole chromosome painting

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Pelz AF, Weilepp G, Wieacker PF
Cancer Genet Cytogenet. 2005 Jan 1; 156(1): 59-61
Chronic myelogenous leukemia (CML) is a clonal bone marrow disease with progression from a chronic phase to an aggressive blast crisis. The cell line NALM-1 was originally established by Minowada and coworkers from the peripheral blood of a patient in CML blastic crisis. A karyotype analysis of the NALM-1 cell line was performed in the 1970s. To the best of our knowledge, this karyotype was not re-analyzed by molecular cytogenetic techniques, although this cell line is the source of many molecular investigations including expression studies. To establish this cell line as a CML control in our own laboratory, NALM-1 was analyzed by GTG banding, fluorescence in situ hybridization, and spectral karyotyping. Our results differ from the original publication of Sonta and coworkers. We describe for the first time the karyotype of the NALM-1 cell line: 44,X,-X,der(7)t(7;9;15)(q10;?;q15),der(9)t(9;9)(p24;q33 approximately q34)t(9;22)(q34;q11),der(15)t(7;9;15) (?;?;q15),der(22)t(9;22)(q34;q11).

http://www.hubmed.org/display.cgi?issn=01654608;uids=15588857

A case of myelodysplastic syndrome with acquired monosomy 7 in a child with a constitutional t(1;19) and a mosaicism for trisomy 21

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Hu J, Shekhter-Levin S, Shaw PH, Bay C, Kochmar S, Surti U
Cancer Genet Cytogenet. 2005 1 1; 156(1): 62-67
A 3-year-old patient presented with anemia, thrombocytopenia, and blasts in the peripheral blood. A bone marrow aspirate revealed a myelodysplastic syndrome (MDS). A mosaic abnormal female karyotype 46,XX, t(1;19)(q42; p13.1)c[12]/ 47,idem,+21c[3]/ 47,idem,-7,+21c,+mar[7] was obtained on G-banded metaphases from unstimulated bone marrow aspirate cell culture. To rule out constitutional abnormalities, we performed a cytogenetic analysis on the patient’s phytohemagglutinin-stimulated peripheral blood and cultured skin fibroblasts. A karyotype of 46,XX,t(1;19) (q42;p13.1)c was found in all 20 peripheral lymphocytes analyzed, confirming the constitutional origin of the translocation. In addition, 5 out of 50 cells from two separate cultures of the skin fibroblasts contained an extra chromosome 21. The presence of two cell lines in multiple cultures indicates that the patient is a true low-level mosaic for trisomy 21. Because of the finding of monosomy 7 and a marker chromosome only in the trisomy 21 clone, we conclude that the leukemic clone arose from a hematopoietic precursor with constitutional trisomy 21. It is also possible that the t(1;19) played some role in the development of the MDS. Because acute myelogenous leukemia (AML) and MDS with Down syndrome (DS) have distinct biologic and clinical features, the identification of DS patients with a mild or normal phenotype in the AML/MDS population is of fundamental importance for clinical diagnosis and management.

http://www.hubmed.org/display.cgi?issn=01654608;uids=15588858

Localization of bone morphogenetic proteins (BMPs)-2, -4, and -6 within megakaryocytes and platelets

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Sipe JB, Zhang J, Waits C, Skikne B, Garimella R, Anderson HC
Bone. 2004 12 ; 35(6): 1316-1322
In this study, we localized bone morphogenetic proteins (BMPs), proteins known to induce ectopic osteogenesis, within megakaryocytes and in lysates of human platelets. Immunohistochemistry localized BMP-2, -4, and -6 within marrow megakaryocytes of 5-week-old rat tibias. In situ hybridization was utilized to confirm the presence of BMP-2, BMP-4, and BMP-6 mRNA in 2- to 3-week-old mouse tibial marrow megakaryocytes. Finally, the presence of BMP-2, -4, and -6 was confirmed in human platelet lysates using Western blot technique. The expression and release of BMPs by megakaryocytes, within platelets and perhaps by secretion, may help to explain recent reports of excessive bone formation associated with increased numbers of marrow megakaryocytes in GATA-1- or NF-E2 gene-deficient mice. Also, excess local release of BMPs may provide an explanation for the bone overgrowth (osteosclerosis) seen in human patients suffering from a type of myelogenous leukemia characterized by increased numbers of marrow megakaryocytes.

http://www.hubmed.org/display.cgi?issn=87563282;uids=15589212

Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics

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Fang B, Zheng C, Liao L, Han Q, Sun Z, Jiang X, Zhao RC
Blood. 2004 12 9;
Overwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. Interestingly, the BCR/ABL fusion gene, which is present in chronic myelogenous leukemia (CML), was also detected in the endothelial cells of CML patients, suggesting that CML might originate from hemangioblastic progenitor cells that can give rise to both blood cells and endothelial cells. Here we isolated Flk1(+) cells carrying BCR/ABL fusion gene from the bone marrow of 17 Ph(+) CML patients and found that these cells could differentiate into malignant blood cells and phenotypically defined endothelial cells at the single cell level. These findings provide direct evidence for the first time that rearrangement of BCR/ABL gene might happen at or even before the level of hemangioblastic progenitor cells, thus resulting in detection of BCR/ABL fusion gene in both blood and endothelial cells.

http://www.hubmed.org/display.cgi?issn=00064971;uids=15591120

Imatinib (Gleevec(R))-induced Hepatotoxicity

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Ayoub WS, Geller SA, Tran T, Martin P, Vierling JM, Poordad FF
J Clin Gastroenterol. 2005 1 ; 39(1): 75-77
Imatinib (Gleevec(R), Novartis Pharmaceuticals Corp, East Hanover, NJ) is widely used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. To our knowledge, only one case report of histologically proven Imatinib-induced hepatotoxicity has been reported. We describe another case of hepatotoxicity in a 22-year-old woman including the histopathologic changes and the clinical course after the discontinuation of Imatinib.

http://www.hubmed.org/display.cgi?issn=01920790;uids=15599217

Pic Of The Day

Posted by rob on December 16, 2004 under Uncategorized | Be the First to Comment

Giant Christmas baubles containing Christmas trees sit in the prestigious Place Vendome in Paris.

Some Photos Of Chelsea

Posted by rob on December 15, 2004 under Uncategorized | Be the First to Comment

Chelsea and cousin Emily, 8/04

Chelsea, Aunt Lori, and Emily (Lori’s daughter), 8/04

Development of c-Kit-expressing small-cell lung cancer in a chronic myeloid leukemia patient during imatinib treatment.

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Gambacorti-Passerini C, Piazza R, Tornaghi L, Pilotti S, Pogliani E
J Natl Cancer Inst. 2004 Nov 17; 96(22): 1723-4
 
No abstract

http://www.hubmed.org/display.cgi?issn=14602105;uids=15547187

Imatinib mesylate may improve fasting blood glucose in diabetic Ph+ chronic myelogenous leukemia patients responsive to treatment.

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Breccia M, Muscaritoli M, Aversa Z, Mandelli F, Alimena G
J Clin Oncol. 2004 Nov 15; 22(22): 4653-5
 
No abstract
http://www.hubmed.org/display.cgi?issn=0732183X;uids=15542819

The influence of St. John’s wort on the pharmacokinetics and protein binding of imatinib mesylate.

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Smith P
Pharmacotherapy. 2004 Nov ; 24(11): 1508-14
STUDY OBJECTIVE: To determine the effect of St. John’s wort on the pharmacokinetics of imatinib mesylate. DESIGN: Open-label, complete crossover, fixed-sequence, pharmacokinetic study. SETTING: Clinical research center. SUBJECTS: Ten healthy adult volunteers. INTERVENTION: Single 400-mg oral doses of imatinib were administered before and after 2 weeks of treatment with St. John’s wort 300 mg 3 times/day. MEASUREMENTS AND MAIN RESULTS: The pharmacokinetics of imatinib were significantly altered by St. John’s wort, with reductions of 32% in the median area under the concentration-time curve from time zero to infinity (p=0.0001), 29% in maximum observed concentration (p=0.005), and 21% in half-life (p=0.0001). Protein binding ranged from 97.7-90.3% (mean 94.9%), was concentration independent, and was not altered by St. John’s wort. Therapeutic outcomes of imatinib have been shown to correlate with both dose and drug concentrations. CONCLUSION: Coadministration of imatinib with St. John’s wort may compromise imatinib’s clinical efficacy.

http://www.hubmed.org/display.cgi?issn=02770008;uids=15537555

[Imatinib–a new perspective in the treatment of tumors]

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Klener P, Klamová H
Cas Lek Cesk. 2004; 143(9): 579-80, 582-3
Among novel promising approaches to anticancer therapy belongs the targeting inhibition of signal transduction. This review outlines present-day experiences with imatinib (Glivec), a potent inhibitor of the tyrosine kinases bcr-abl, c-kit and platelet-derived growth factor receptor kinase. Due to inhibition of bcr-abl tyroxine kinase, imatinib has rapidly become the standard therapy for chronic myelocytic leukemia; inhibition of c-kit receptor explains its effectivity in the treatment of patients with gastrointestinal stromal tumors. Another known target of imatinib is tyrosine kinase of PDGFR, which is activated in numerous malignancies, particularly in dermatofibrosarcoma protuberans. Discovery of the novel fusion gene in hypereosinophilic syndrome (FIPILI-PFGFRA, whose product is an imatinib sensitive protein kinase) permitted to treat successfully this event. Possible combination of imatinib with conventional chemotherapeutic drugs and other key signal transduction inhibitors are mentioned.

http://www.hubmed.org/display.cgi?issn=00087335;uids=15532894

Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in chronic myeloid leukemia patients treated with imatinib.

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Loriaux M, Deininger M
Leuk Lymphoma. 2004 Nov ; 45(11): 2197-203
Treatment of chronic myeloid leukemia (CML) with imatinib (Gleevec) induces a much higher rate of partial and complete cytogenetic responses (CCR) than interferon-alpha (IFN)-based therapies. Conventional wisdom suggests that elimination of the Philadelphia (Ph)- positive cells will lead to re-establishment of normal Ph-negative hematopoiesis. Surprisingly, karyotypic abnormalities were detected in the chromosome negative cells of some patients with cytogenetic response to imatinib. In some cases, this was associated with a myelodysplastic syndrome (MDS). While clonal evolution in Ph-positive cells is considered part of the progression of CML, clonal evolution in Ph-negative cells had been observed only rarely in a small number of patients treated with IFN or bone marrow transplantation, raising the question whether the phenomenon may be causally linked to imatinib therapy. In this manuscript, we will review the currently available data, suggest possible causes and discuss potential implications for patient management. We are fully aware that a systematic study of a larger patient cohort will be required to conclusively address these issues.

http://www.hubmed.org/display.cgi?issn=10428194;uids=15512807

Pic Of The Day

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As the first signs of winter push into the Northeast, Cornell University researchers have some good news for fair weather fans, spring is coming a week earlier than it did 40 years ago. The lilacs say so. In one of the most comprehensive studies that plants in the Northeast are responding to the global warming trend, Cornell scientists and their colleagues at the University of Wisconsin found that lilacs are blooming about four days earlier than in 1965.

Kinder, gentler procedure gives superior results for stem cell transplants

Posted by rob on December 14, 2004 under Uncategorized | Be the First to Comment

Contact: Gwen Ericson
ericsong@wustl.edu
314-286-0141
Washington University School of Medicine

 

St. Louis, Dec. 13, 2004 — An improved stem cell transplant regimen that is well-tolerated and has a high success rate has been developed by researchers at Washington University School of Medicine in St. Louis. The procedure holds promise for treatment of blood and bone marrow disorders, immune dysfunction and certain metabolic disorders.

Designed for transplants that replace a patient’s bone marrow with stem cells from donor marrow, peripheral blood or umbilical cord blood, the procedure allows early recovery of immune function, nearly eliminates transplant rejection, and decreases the incidence and severity of “graft vs. host disease,” a common complication in transplants.

Termed a “reduced-intensity” protocol, in pediatric patients it may minimize damage to sensitive growing tissues like the brain and reproductive organs.

The pilot study of the procedure is reported in the journal Bone Marrow Transplantation. It is available through advance online publication on Dec. 13 and will appear in a future print issue.

The regimen was administered to 11 pediatric and 5 adult patients at St. Louis Children’s and Barnes-Jewish hospitals and the Children’s Hospital of New Orleans who had non-malignant bone marrow or metabolic disorders such as sickle cell anemia, thalassemia or Hurler’s syndrome. Symptoms and disease parameters stabilized or improved in all patients that underwent successful transplants.

In a successful stem cell transplant, the donor stem cells become permanently established, or engrafted, in the patient’s bone marrow and continually produce healthy blood cells. To prevent the host immune system from destroying the foreign stem cells, physicians administer a pretransplant immune suppressing treatment.

“We wanted an approach that would effectively knock out the patient’s immune system to let the transplanted cells engraft, but then allow immune function to recover quickly,” says study leader Shalini Shenoy, M.D., assistant professor of pediatrics and faculty member of the Siteman Cancer Center.

A key innovation in this study changes the timing of administering a powerful pretransplant conditioning drug. The drug, Campath-1H, targets and destroys several vital immune system components. Previous studies used Campath-1H in higher doses and gave the drug at transplant time. With such dosing, Campath stayed in the body for up to 56 days after the transplant.

“We give a short, three-day, lower-dose treatment of Campath, three weeks in advance of transplant,” Shenoy says. “As a result, we ensure that Campath levels are lower by the time of transplant to help establish donor cells and allow early recovery of immune function.”

With standard transplant protocols, immune function may not fully recover for a year or more, and during this time, the patient is highly susceptible to life-threatening infections. In this study, the patients’ immune function showed significant recovery by six months, and no major infections were encountered after this period.

Fourteen of the 16 patients had successful bone marrow engraftment of the donor stem cells and only one experienced late graft rejection, an unusually high rate of success according to Shenoy. Furthermore, the grafts took hold quickly. Donor stem cells had established in the bone marrow completely at one month, contrasting with other reduced-intensity protocols where donor engraftment is gradual and often takes many months.

The protocol also reduced the incidence and severity of graft vs. host disease, which occurs when transplanted immune cells attack various cells in the body. For the majority of patients who experienced graft vs. host disease, the symptoms were limited to the skin and were controlled with treatments that were later successfully withdrawn.

To minimize damage to still-growing tissues such as the brain and reproductive organs in pediatric patients, the protocol uses smaller doses of standard conditioning chemotherapeutic agents.

“In the past, physicians had to accept the potential for brain damage or sterility in pediatric patients treated with chemotherapy,” Shenoy says. “We’re trying to provide treatments that protect developing tissues. We’ve had our first pregnancy and normal delivery in one of our stem cell transplant patients, so we think the protocol offers some hope.”

Next, Shenoy plans to evaluate whether changing parameters and further reducing chemotherapy doses would enhance the protocol’s effectiveness. She will also conduct studies targeted at sickle cell anemia and chronic myelogenous leukemia to explore the potential for successful transplants in children with these disorders.

###

Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ, Mohanakumar T, Rao A, Hayashi RJ. A novel reduced intensity stem cell transplant regimen for non-malignant disorders. Bone Marrow Transplantation, upcoming issue.

Funding from St. Louis Children’s Hospital Foundation supported this research.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

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