On Friday we met with Dr. P, one of the Duke Medical Center docs who will be treating Zoe once we confirm her need for a Stem Cell Transplant. Prior to the meeting, Michelle and I drew up a list of questions which we had not been able to answer for ourselves, or couldn’t answer definitively.

I’ve left a few questions we asked off for personal reasons, but for the most part this list is complete.

It’s a testament to how well Dr. P covered the bases that, by the time he was done, most of our questions were already answered.

How have things improved since HLH-2004? I notice some stories/cases online with poor outcomes. Can you tell us about what’s improved in recent years?

Much has improved. New medicines and a better understanding of when to be aggressive and when to ease back have improved survival rates for HLH patients. In addition increased awareness allows for faster diagnosis; faster diagnosis means less harm to the body and greater chance of surviving a transplant.

We’ve found that the stories posted online tend to be those families who have suffered poor outcomes, unfortunately, making the picture appear slightly more dire than it might be. Dr. P confirmed that that was his experience too, more families who have lost children take the time to memorialize them online (with good reason) than do survivors.

Statistics? Rates of survival with newer procedures, cord blood, 5/6 match, infants vs toddlers

As discussed, statistics are skewed by the rarity of HLH and the inclusion of patients who did not benefit from recent advances in treatment. Typically pegged at 70%, rates of survival are likely much higher now when the disease is diagnosed early.

Cord blood offers reduced risk of Acute Graft Versus Host Disease, one of the two main risks of the transplant; it’s the best possible treatment short of a sibling match.

A 5/6 HLA match is very good; A 6/6 match would potentially offer a few percentage points more average success rate, but is generally very rare.

Infants tend to have slightly better chances of survival due to resilience and size — the transplant material is higher saturation in a smaller body, and higher saturation is good.

Has duke done any hlh patients recently? did they make it?

Since 2000 all HLH transplant patients have survived. Some live with side effects of the treatment and transplant and some are back to near “normal”.

Can we do a low-intensity transplant?

No. These are typically used for older patients who are unlikely to survive a normal transplant/conditioning regimen due to other health problems.

Is total body radiation necessary in non-cancer patients?

No. Zoe will not receive total body radiation, thankfully.

This treatment is more typical in cancer-related transplants or where there is a need for a targeted “nuke” to a malignancy. Zoe has a disease that would not be likely to be treated with external radiation.

Which meds are typically given for the conditioning regimen? (Campath? vp-16?)

Busulfan, Cyclophosphamide, and ATG.

Some patients get Campath as an alternative to ATG. Both use animals (gerbils? in campath, horses or rabbits in ATG) to incubate antibodies to help prevent transplant rejection. Both tend to involve some level of allergic reaction, but are nevertheless necessary. The allergic reaction is expected and treated as part of the conditioning process.

Zoe had a slight allergic reaction to vp-16 that was mitigated with benadryl, will she need something else if she cannot take high doses of that?

She is unlikely to need VP-16/Etoposide at all once the transplant process has begun.

Side effects — puberty, growth, physical disability, relapses?

Side effects are common and vary widely. Slowed puberty and slightly reduced growth are common. These are not as great as feared, however. The puberty issue can be resolved via monitoring and possibly some intervention if she is delayed, and the growth reduction is typically relatively minor. The example Dr. P gave was the cumulative effect of the treatment and her medications might cost Zoe ~2 inches in growth vs what her height might have been without. Her build/weight should be about what it would have been otherwise.

Her risk of cancer is elevated, something on the order of 2-3% higher. That means if she has a 12 percent chance of breast cancer in her life, she will now have closer to a 15% chance.

Neurological problems stemming from her treatment are possible, but are not as severe or likely as we feared. Examples given were trouble with higher math in high school or above, or need to utilize redundant study methods (taking notes and taping a lecture, for example, to help retention).

Severe disability overall is unlikely in a child like Zoe who does not have other underlying problems.

SCT should be curative, relapses of the kind a Leukemia patient might endure are unlikely.

Will Zoe need growth hormone or estrogen?

Very unlikely to need growth hormone. Might need estrogen if puberty is slow to start.

A lot of the poor-outcome stories I’ve read involve VOD — have any methods evolved in the past couple of years to mitigate the high chance of it, or is it still ~40%?

The risk of some VOD is still there, but new treatments using Defibrotide reduce the overall risk of death. So yes, methods have evolved and it is not nearly the risk it used to be.

Overall risk of getting VOD is closer to 10%, not the 30% sometimes seen in older literature, and the rate at Duke specifically has been only 5%.

We understand Zoe is a 5/6 match to the cord blood, a 3/6 match to Maya — are there any other donor options that could offer a higher match rate we should consider? Is a 5/6 match going to give her her best chance vs a ‘perfect’ match?

A cord blood 5/6 match is her best bet short of a better sibling match. No other donor options could offer a higher match. A perfect match would offer only a couple percentage points advantage.

What do we expect zoe’s physical condition to be at different phases — first 2 weeks, can we move her, hold her, can she nurse etc? after a month? after the 50 days?

The most difficult phase will be the first 2 weeks. We will be able to hold her and nurse her if she is willing, but she may not be willing for a period of time if she has mouth sores or poor appetite. She will be on IV nutrition regardless. Her condition should improve greatly by the end of the 45-50 day inpatient stay if she is on track.

Do parents room in with children? Is it best for there to be one person for the duration or can we rotate?

Yes one parent rooms in, and in fact a caregiver must be with her at all times. We can rotate caregivers.

Isolation: who can visit, family, room restrictions, can we bring in food, computers, etc.

Risk of infection is the driving force here, and the entire PBMT ward is in an “airlock” of sorts. Positive pressure, it’s called. When someone leaves, air only moves out of the ward, never in.

Visits are strictly limited to healthy people. Shoes must be wrapped, hands washed. Food is allowed (but no leftovers), as are computers and outside conveniences.

In the outpatient apartment, does she have to stay inside all the time? Does she have to stay inside for the year or is it only busy locations we have to avoid?

By the time the ~45 days have passed, if we are able to move to an outpatient status, she will be able to go outside and do most things. She will need to avoid busy places.

How soon should we move ahead? We understand that catching the disease early is very important to survival.

We have already gained control over the disease itself. The next step is to confirm the need for the transplant and then ensure Zoe is in the best possible condition to start. This should all happen in coming month or two.