The need to preserve hope

...The ones his body produced were not from Beverly's marrow, but the small, dysfunctional ones characteristic of Wiskott-Aldrich syndrome...

...He says the Wiskott-Aldrich experience was, in a way, like gene transfer—the technologyinthe-making where defective cells are extracted, altered to make them healthy, and reinserted...

...His limp is the result of a clot that formed around the shunt he had during the transplant, so that blood could be drawn and medications administered...

...Patrick's older brother Christopher died of WiskottAldrich at the age of four...

...It's just awful, how Scott and I are healthy, and they are sick...

...You're taking an exogenous source of the gene—cloned by mother nature, rather than in the laboratory," says Rappeport, "but you are putting in a new gene...

...In the intervening years, too, hospital stays have been gradually reduced for bone marrow transplants, and the therapy's applicability has been broadened...

...Rappeport: "T cells which he had not had before—were donor, but over a period of months they began to fall in number...

...And (Continued on page 19) 14: 27 March 1992 Commonweal (Continued from page 14) I know when he was younger the kids used to give him a hard time about that...

...With her grief over Christopher's death still fresh, Pam Hough would stay at the hospital each day until Patrick took his bowel prep, the disgusting-tasting gastrointestinal antibiotic Rappeport's bone marrow transplant patients take several times a day...

...It's important to remember, too, that palliative treatment, such as that given Christopher Hough, can be more expensive—financially as well as emotionally— than that which is curative...

...The outcome for Patrick, despite the difficulties and hardships he's had, is infinitely preferable...

...But analysis of Patrick's continuing illness and treatment pointed to a critical breakthrough and ultimately a cure...

...B cells were his own...

...They were so little...

...He is about five feet, two inches, though his mother and father are both tall and Beverly is six feet...

...WiskottAldrich patients sometimes die of tumors, as well as from bleeding and infection, and people who have had bone marrow transplants sometimes develop tumors as a result of the immunosuppression of chemotherapy and radiation...

...He pressed for a second transplant, to be done this time with more intensive preparation, so as to eradicate the stem cell...

...Beverly saved Patrick's life...

...I remember my parents weren't around...

...The eczema was a torment...

...Because laboratory tests showed that the first transplant had sensitized Patrick to Beverly's marrow, Commonweal 27 March 1992: 13 graft rejection was likely, and so additional immunosuppressants were given for the second transplant...

...That is, with reasonable reliability but not certainty...

...At the time, Rappeport had used only immunosuppressive drugs...

...I don't know why...

...Christopher was bleeding internally, his eyes were crossing, and he had terrible eczema...

...At first entirely experimental, they are now therapy for a number of diseases, in fact, the treatment of choice for some...

...The Houghs are now divorced...

...When a bone marrow transplant is decided on, it is nearly always because there is no other realistic hope for the patient...

...But to Rappeport it was clear that Patrick would die without a second transplant...

...In the course of my research, I met and interviewed other of his patients, including Patrick Hough, Patrick's mother, Pamela, and Patrick's sister Beverly...

...You know, research...

...When bone marrow fails to produce red cells to carry oxygen, platelets to clot, and white cells to fight infection and provide immunity, the patient dies...

...It was awful...

...Patrick had not been cured...

...We cannot let our fear of the unknown, and our well-founded skepticism and frustration at human inadequacy, make us turn away from the effort to save life, especially young life...

...Patrick continued to need platelets...

...They shared the story of the long, complex treatment Patrick underwent for Wiskott-Aldrich syndrome...

...Rappeport's unwillingness to allow himself to become discouraged saved Patrick Hough...

...Beverly's healthy marrow had not firmly engrafted...

...Until the new bone marrow takes hold and begins to grow, the slightest infection could prove fatal...

...his veins had collapsed...

...But she wouldn't show that to us...

...I remember celebrating his birthdays in the hospital...

...It just didn't seem right...

...More is known: about blood, about genetics, about all of biology...

...he baby-sits for two retarded people, twins...

...Rappeport believes his success with Wiskott-Aldrich syndrome is representative of a kind of experience that he sees as virtuous, endangered, and necessary: clinical research—learning through the attempt to cure...

...He likes to talk and has a lot of feelings and a lot of emotions, but he never just lets himself go and says it...

...I just couldn't go through that again," Beverly says...

...I could sit and talk with Patrick for hours and hours and hours, and we won't get bored...

...Rappeport reasoned that it was the preparation that had been faulty in Patrick's first transplant...

...Science does lead to the cure of dreadful disease...

...Now over fifteen years later, she is still full of concern for him, alert to any slights he receives...

...Rappeport said so, and his superiors and the Houghs finally agreed to his proposal...

...His legs are really scarred and everything from the shunts...

...Beverly, who served as Patrick's donor, has not yet been tested to see if she is a carrier of Wiskott-Aldrich, although it is now possible for her to find out...

...Beverly says that she would not have a child if there were even the slightest chance that he could have Wiskott-Aldrich syndrome...

...The cells were type 0, Patrick's original blood type, rather than A, Beverly's, and chromosomal analysis showed a high percentage of the granulocytes—another type of blood cell—to be male...

...they live two houses down...

...He'll talk to me, because we have this weird connection...

...more and more lives are being saved, often with less financial cost and less agony than used to be the case...

...He shoots baskets, plays floor hockey, wrestles...

...He's smart...

...Patrick, she says, "would open his mouth and his skin would split and bleed...

...He underwent two bone marrow transplants, the first when he was three and a half, and the second when he was five...

...Patrick, too, likes sports...

...It's work he likes...

...Pamela Hough was pregnant with Patrick when Christopher was diagnosed with the condition...

...But Christopher, the third child, was not...

...Wiskott-Aldrich syndrome is an extremely rare disease—there are only a handful of cases every year in the world—but common and uncommon genetic disease will always be with us, a fact guaranteed by the process of mutation, which is an essential factor in evolution...

...Christopher's death, after a short lifetime of pain and sickness, was a tragic, heart-breaking fate for him and his whole family...

...But we'd try to help him get through his bowel prep...

...Because only boys are afflicted, Beverly, second in the family, was never in danger...

...And with that observation we realized [Patrick] had engrafted only what wasn't there, and that not permanently...

...Children with Wiskott-Aldrich syndrome have insufficient and abnormal platelets and T cells (a type of white cell) and are therefore subject to constant and extreme bleeding and infection...

...Scott is a huge guy, six foot six, a professional football player...

...His or her bone marrow, unlike solid organs, regenerates within weeks...

...If I were her, I think I would have fallen apart...

...Because he wants it so bad...

...The alternative, however, is nearly always death...

...His face was all broken out, and his eyes and his mouth...

...But that wasn't the source of the problem...

...He also had cataracts, almost surely because of radiation...

...Nevertheless, the fact that absent T cells and defective platelets—cells that descend from different lines—caused Wiskott-Aldrich pointed to the need to eliminate the abnormal pluripotent stem cell, the root of all blood production, and as Rappeport explains, to create "space, not physical space, but some other kind of hematopoietic space," in which the transplanted marrow could thrive...

...We were little, too...

...There was a clue, however...

...She was around seven when Christopher lay dying, and remembers it well...

...Abortion is unacceptable to many people, and, in any case, ineffective against many of the extreme misfortunes of catastrophic illness...

...In 1976, when doctors first tried a bone marrow transplant for three-and-a-half-year-old Patrick Hough, there had never been a fully successful one for Wiskott-Aldrich syndrome...

...In an allogeneic bone marrow transplant—one in which someone other than oneself or an identical twin is the donor—the patient's bone marrow is destroyed with chemotherapeutic drugs and/or radiation, and is then replaced with healthy marrow...

...In Wiskott-Aldrich syndrome illness comes from an insufficiency of working cells rather than from the aggressiveness of malignant ones...

...Beverly, talking separately, agrees, "I can't explain it...

...And yet, since 1976 Rappeport has transplanted a number of children with Wiskott-Aldrich syndrome and, with the exception of one boy whose donor was a genetic half-match, all are now healthy...

...And whatever he does, he'll do well...

...Still, bone marrow transplants are risky and involve both high financial costs and prolonged periods of sickness, fear, and isolation...

...What befell the Houghs can happen, in the form of one disease or another, to anyone...

...And a big belly...

...The drug was discontinued...

...For the recipient, however, the situation is extremely dangerous...

...Then Patrick developed an infection, and "in late June, his [hemato] crit dropped," a side-effect of Bactrim, the antibiotic Patrick was taking...

...But we also need to think about the cost and grief of not making that effort, of not trying to save a life, and then, when such efforts prove successful, about their great value to other people...

...There were nurses who didn't look after him properly, who let him lie in his own vomit and diarrhea, so that Pam, coming in to see him, would scrub and gown and glove in the requisite way before going into his sterile room—it took her ten minutes— and then go in and clean her child, flinging the filthy sheets out of the room...

...The drugs used to destroy the original disease and to suppress the patient's immune system (so that the new marrow will not be rejected) endanger every organ in the body, and can have horrendous consequences, including death...

...Patrick Hough, now in his late teens, was one of the first to undergo a transplant for Wiskott-Aldrich syndrome...

...He can do anything...

...Then we'd leave for the night...

...Bone marrow transplants have been available since the 1960s...

...And then rub them down with tar cream...

...it was odd...

...It's awful to have a bone marrow transplant...

...They would make him do it three times, and after the third time they wouldn't make him do it again...

...The clot extended into the arteries, Rappeport says, preventing one leg from growing properly for a while...

...Bone marrow is the body's blood producer...

...Now in his late teens, Patrick is healthy, but he is short, also presumably as a result of the radiation he received...

...But he's very, very determined...

...So I said, `No, I don't want it...

...And I think that's kind of what's most disturbing about it...

...Patrick is quiet and gentle...

...But Patrick survived the episode and the others that followed...

...Surgery to remove the tumor caused excruciating pain...

...Even when the bone marrow transplant goes smoothly, the patient has a long hospitalization, experiences intense sickness and weakness, and, once home, faces a long period of recuperation, during which everything has to be kept scrupulously clean, and physical—and even social—contact with other people is largely denied...

...There was never any hope for him, because the only possible cure was a bone marrow transplant, and Christopher did not have a compatible donor...

...And the skin would get infected and have kind of a smell, an odor to it...

...It was looking carefully at what happened, coming to a conclusion, and trying to solve the problem...

...She is anxious about the possibility of more bad health befalling him...

...A bone marrow transplant either replaces diseased marrow (as in leukemia) or supplies a lack of marrow (as in aplastic anemia...

...My tummy!' and he'd throw it up...

...Solutions often don't come smoothly or easily, and can involve uncertainty and terrible suffering...

...He doesn't get discouraged...

...Patrick wouldn't let visitors touch the bed he was in, let alone touch him...

...Scott, the oldest, was also spared...

...Should Beverly turn out to be a carrier, there is also a prenatal test for the disease, making abortion an option...

...They thought Patrick wouldn't survive it," says Rappeport, "and called us Nazis...

...And despite his normal, perhaps high, intelligence, he has trouble reading and writing because of learning disabilities, presumably caused by the battering his body took so he could live...

...Wiskott-Aldrich syndrome is a genetic disease that is passed from mother to son, and that, until bone marrow transplants were used to treat it, invariably killed its victims in childhood...

...We stayed at the 0' Briens' house...

...His [blood] counts were rising," Rappeport says...

...THE NEED TO PRESERVE HOPE MADELINE MARGET THE PAINS & GAINS OF MEDICAL PROGRESS When we look at the anguish of a patient and his or her family and the expense of radical efforts to cure a serious, even fatal illness, it is easy enough to understand why we would want to place limits on heroic or experimental procedures...

...Bone marrow transplants are usually undertaken in an effort to save young lives, and they often succeed...

...But right through her telling she indicates, sometimes just with a hand gesture, a seconds-long imitation of the dismissal or brusqueness or lack of feeling she endured under the more or less constantly horrendous conditions of drawn-out critical, but potentially curable, illness...

...Eventually, Christopher needed an incision in his neck for an IV...

...Christopher was in the hospital for months with chicken pox...

...He thinks he would like to be a gym teacher, perhaps for special-needs kids...

...The doctors hadn't known what was wrong with Christopher at first, and when they found out, they didn't explain it clearly to the Houghs...

...She was a wreck, physically and mentally, because Christopher died, and Paddy was going through the same thing...

...Over the decades, they have become safer, and the hospital stays for recipients shorter...

...And then put little nightcaps on them and cover their hands up, because they would scratch so hard they would bleed...

...We can tell for sure by twenty weeks of gestation," Rosen says...

...He almost died of pneumonia when he was only a few weeks old...

...Because children with Wiskott-Aldrich syndrome have abnormal lymphocytes, their bodies can't fight infections effectively...

...Myeloid cells his own...

...But it just never seemed right...

...He had a color TV and a telephone, and all his sterilized toys and food...

...It was just too painful...

...She doesn't know if it has anything to do with her having been his donor, but she says, "We're really, really close...

...It was awful," Pam says...

...I think my mother's very strong...

...He was given platelet transfusions periodically while the doctors decided what to do...

...And so, for several years, Pam Hough had two acutely ill children to care for...

...I couldn't have done that and still lived...

...And there were big clumps on his head...

...At first it seemed to take...

...And he had skinny, skinny legs and arms...

...And God, I remember the way Christopher always looked...

...He and Paddy were always sick...

...For both little boys, there was hospitalization after hospitalization...

...Of the doctors Pam says, "they were all very good...

...The procedure has led to a greater understanding of not only normal physiology, but of illness and cure in general...

...We'd all get dressed up and bring his cake and everything and have his cake in the hospital...

...We can diagnose carriers with confidence," says Fred Rosen, an immunologist who worked with Rappeport...

...12: 27 March 1992 Commonweal Joel Rappeport, who cared for Patrick during his transplants, is a cranky, chainsmoking, disheveled, always exhausted-looking, and very dedicated doctor...

...All the choices can seem untenable...

...In the hospital, "there were tests," said Pam...

...I don't know if it has all come from his past experiences or whatever...

...That effort, bringing hope, is surely a necessary and virtuous thing...

...I used to put out two bathtubs, and give them oatmeal baths...

...His red cells were his own...

...He walks with a limp, and I remember girls laughing and imitating him...

...But, says Beverly, "he has a lot to say...

...tracing a mature cell back to its origins can reveal the problem...

...he Houghs' story is the reality of medical and scientific progress...

...So it was reasonable for Rappeport and his colleagues to assume that they did not have to eradicate Patrick's marrow, but simply get healthy marrow into him...

...Though this happened long after the transplant, it was a terrible scare...

...It wasn't a planned attack," Rappeport says...

...I have spent several years studying and pondering this issue, first, when my sister, Roberta, was diagnosed with a rare and deadly form of leukemia and, then, in writing a book about the work of Joel Rappeport, the hematologist who treated her (Life's Blood, Simon & Schuster, $23, 301 pp...

...Patrick did: his sister Beverly, who is now a young woman in her early twenties...

...He is also intent upon learning as much as possible from each procedure, so as to increase the chances of cure for future patients and in order to help eradicate the terrible diseases he is contending against...

...while he or she is anesthetized marrow is drawn from the pelvis through hundreds of aspirations...

...Therefore, abortion isn't always a solution even for people who are willing to consider it...

...He was always sick...

...And they would give them shots other times...

...Patrick Hough's first transplant took place in May 1976...

...And then when he was in sixth grade, Patrick developed a leg tumor that looked malignant but turned out to be benign...

...Afterward, the donor, usually a sibling, is sore and tired but incurs only very slight risk...

...Often in genetic disease, however, no family history serves as a warning...

...Other doctors in other places have used the procedure to cure many more children...

...Wherever he is, and whatever the specifics of a patient's illness, Rappeport is obsessed with the details—drug doses, urine output, molecular change of disease and cure...

...In naming these cells Rappeport was not only identifying them, but indicating his thinking: blood's components develop from several cell lines...

...That's it.'" The Houghs took him home, and he died a few months later...

...There were other signs that the graft hadn't taken...

...It was really hard...

...This is supplied by the donor...

...He is in his early fifties, and has been performing bone marrow transplants all of his professional life, first in Boston (where Hough was treated) and now in New Haven...

...She remembers, "Patrick would cry, 'My tummy...

...It was just an awful time...

...Commonweal 27 March 1992: 19...

...I think that's the most painful kind of experience, when people don't understand...

...Patrick, on the other hand, was diagnosed in infancy...

...Rappeport's colleagues, especially his superiors, were reluctant, to say the least, to go along with a second attempt...

...She says of her mother, simply and with assurance, "She's a good person...

...We evaluated him extensively," Rappeport says...

...In many ways, bone marrow transplantation is archetypical modern medicine...