Does TB causes Marrow failure?

[mahendra_413]

This is Mahendra.K Patient's father.
My son aged 1 year now under gone PBSCT(Peripheral blood stem cell transplant) in C.M.C hospital, Vellore, T.N, India on 23rd November 2016.

Prior to the transplant he was diagnosed that suffering from Sever combined Immune deficiency(SCID - T-, B+, NK-) along with TB in the month of September 2016.
He was admitted in hospital due to the recurrent infections with fever.

Once the baby was well and the fever settled down the doctor suggested to start the PBSCT process and my Daughter was the HLA matched donor.

The transplant was done on 23rd Novemebr 2016. The WBC engraft was started on 11th day of the transplant.
The WBC was coming up and going down. So they prescribed the growth factor injection and the WBC use to come up.
Baby was present in BMTU for 30days and was shifted to ward.

We started see the nodules under the skin through out the body. The biopsy reported that TB and the TB medicine was continued which was same as the one prescribed before transplant.

The type of the TB was disseminated TB.

the 30days and 60 days chimerism shows 100% donor cells.

Since the platelet count was 400 during the 6th week, they did bone marrow biopsy and the culture was shown TB and the other cell and platelet en-graft cells were present as normal marrow as per the discussion with doctor.

Now the day 90 chimerism results yet to come.

The Ca level (calcium level) in blood is going up. The PTH values is low and the vitamin D-1 test(25-Dyhydroxy)results shows 200pg/ml(the normal value is 19.9 - 79.3) which is more Vitamin D-2.
Hope this huge D-2 vitamin will cause more Ca in blood.

Do the TB bacteria cause release of more calcium into the blood?

Now my worry is do this TB bacterial cells causes any damage to the marrow and cause the failure?

Please kindly answer my questions.
______________________________________________
Yekshit. K, 1 year baby boy, SCID, PBSCT on 23rd Nov 2016

[Neil Cuadra]

Mahendra,

Your son has had a rough time in his young life. His sister is a hero for being his transplant donor.

This article reports that TB and aplastic anemia are often seen together, and that TB treatment can also cause marrow problems.

I haven't read anything about TB bacteria and calcium.

[mahendra_413]

Thank you Neil for the reply.

He got first two chimerism (day 30 and day 60) 100℅. But the day 90 chimerisam is mixed(91℅ donor and 9℅ receipient).

Between day 30 and 60 the bone marrow biopsy was done. The bone marrow biopsy culture shown TB bacteria.

My son is still in hospital. His counts are not stable so graphic will be given and platelets transfusion when needed.
Cyclospurin (imuuno supression drug was stopped around day 70).

Asper the discussion with doctor his neutrophils are normal.

Do this mixed chimerism shows marrow rejection( elapse)?

My worry is do the TB bacteria in marrow cause the relapse?

[Neil Cuadra]

Originally Posted by mahendra_413

Asper the discussion with doctor his neutrophils are normal.

That is excellent news!

Do this mixed chimerism shows marrow rejection( elapse)?

This article from researchers in India says that low levels of persisting recipient cells are not always associated with an increased risk of relapse. They are talking about leukemia, but I presume that this applies to other post-transplant chimerism. They say that the bigger concern is when the level of recipient cells increases over time (called progressive mixed chimerism). So the next chimerism test will be an important measure.

That report also states that "On one hand there is the belief that there is a strong correlation between relapse and hematopoietic mixed chimerism, while on the other hand there are reports which show no such correlation."

A more recent article confirms this, saying "Studies examining the predictive ability of percent chimerism have produced conflicting results." They were studying leukemia and MDS patients.

Your concerns about relapse are understandable, but I doubt that anyone can give you a precise measure of the chance of relapse. Even when transplant recipient cells remain, they could be damaged cells that survived the pre-transplant conditioning or they could be healthy cells with no associated risk.

[mahendra_413]

My son got the next chimerism as 81% donor and 19% recepeint.

As per the discussion with the doctor the MC is due to the prednislone(steriod to control the hypercalcemia) which is doing immuno supression prescribed for the hyper-calcemai.

They reduced the dose of Prednislone since the Ca is under control now and sent for the chimerism again.

Waiting for the results.

[mahendra_413]

Hi Neil,
My son's chimerism fallen till 70% donor (30% patient)and Doctor reduced the dose of predneslone (prescribed for the hyper calcemia).

After few days reduced the dosage the chimerism rose to 72% donor (28% patient). Looks his chimerism is improving.

Hoping for the best...!


Thanks,
Mahendra.K

[Cheryl C]

I hope your son's chimerism continues to improve Mahendra. You must be very concerned for your little boy.

[mahendra_413]

Hi Cheryl,

My son's chimerisam had fall to 35% donor. Tried DLI once at the time of 52% donor and helpless.
Only option left over for us is go for next transplant and chance of success is 40% as per the doctor. No option for us. It is really tuff situation. The last 6 months effort gone waste.

Cause for failure is unknown. The marrow biopsy culture was shown TB positive. Looks the TB bacteria is suppressing the cells. He had splenomegaly too that might be another cause for low counts.
He is under growth factor injection till day 180+.

Now he is suffering from respiratory distress and hospitalized since 1st June. Under O2 and IV antibatics. Chest x-ray not show any infection and culture is negative. It looks more of viral infection.

Multiple issues and it's very tuff time to manage.

May be they start the transplant after he recovers.

[Cheryl C]

I'm so sad reading your post, Mahendra.

Does your son get malaria? I was wondering because of his diagnosis of splenomegaly. I have read that parasitic diseases like malaria, which affects the spleen, can cause pancytopenia and other blood disorders. (I myself had falciparum malaria twice while living in the Solomon Islands and have always wondered if there is a connection).

I do hope that your son recovers soon so that you can commence the next phase of his treatment.