A 10-year-old female patient with a history of ALL in second complete remission underwent haploidentical HSCT of peripheral blood depleted with T lymphocytes.
Table 1 shows the results of the usual non-fecundity study in the pre-transplant period of donor and recipient.
The mother was 41 years old, healthy, with positive serology (Ig) for cytomegalovirus (CMV) and Epmer virus negative donor serology (VEG), and positive serology for toxoplasmosis IgM.
The patient had IgG positive for CMV, EBV and herpes simplex virus type 1.
No tuberculosis study was performed.
1.
Upon admission to the transplant unit stood out a eutrophic girl, in good general conditions, healthy skin and mucous membranes, with an implantable central venous catheter with subcutaneous reservoir, normal cardiopulmonary examination, abdominal echocardiography and normal myelogram.
He received a conditioning of reduced intensity with fludarabine, thiotepa, melphalan, total nodal radiotherapy, antithymocyte globulin and rituximab.
Infusion of hematopoietic progenitors depleted T lymphocytes without incidents was performed.
She received fluconazole 400kg IV, cyclosporine and methylprednisolone in the first post-HSCT period, as prophylaxis for infectious diseases 3 mg/kg/day, weekly immunoglobulin 20 mg/15 mg/m, weekly
According to the haploidentical transplantation protocol, follow-up was performed once a week with tapeworm (GM) and viral load for adenovirus (AD V), EBV and CMV from the day of post-HSCT infusion to day 6.
On day 4 she presented fever, chills, odynophagia and pain in the oral cavity.
Laboratory analysis revealed an absolute neutrophil count (ANC) of 0/mm3 and a C-reactive protein (CRP) of 149 mg/L, so empirical antimicrobial therapy with ceftazidime and vancomycin was initiated.
The central hemocultive was positive for coagulase-negative Staphylococcus.
She completed 10 days of treatment with the patient afflictl, in good general conditions, with ANC of 0/mm3, CRP < 20 mg/L, negative control hemocultives and normal echocardiogram.
With respect to hematopoietic reconstitution, the patient achieved implantation with chimerism 100% per day +7, platelets (> 20,000/mm3) and white series (ANC > 500/mm3) at day +10 and red cell series 11.
On day +19 a CMV reactivation was diagnosed, receiving ganvir iv therapy for 21 days and then on manatee doses until day +50, with negative viral loads.
From day +41 presented liquid stools and vomiting.
A probable upper gastrointestinal pathology was diagnosed and treatment with prednisone was started.
The study of stools was negative for bacteria, rotavirus, ADV cocci, Microsporidium and Cryptosporidium spp.
Upper gastrointestinal endoscopy showed mild edema and a stalked image in the gastric antrum.
Biopsy confirmed upper gastrointestinal pathology grade I-II.
On day + 54, the patient again developed fever and general malaise, with no local symptoms on physical examination.
After culture collection, empirical antimicrobial therapy was initiated.
A CT scan of the chest revealed a rounded focal lesion in the left lung base and two mediastinal lymph nodes.
Abdominal CT scan showed multiple focal hypodense liver lesions, with rounded uptake of contrast medium in the periphery, distributed randomly in the liver parenchyma size of 1.3 cm.
1.
In the context of a haploidentical HSCT with a HCM for eventual active tissue conservation, a liver biopsy was performed for histological study, staining, bacterial and fungal culture, as well as a piece of studies.
Antimicrobial coverage was adjusted to meropenem, vancomycin and voriconazole.
The patient remained febrile, with compromised general status, disintegrated stools without respiratory symptoms, with increasing CRP (170-194 mg/L), serial negative GM and normal echocardiography.
The anatomopathological study of the hepatic tissue showed confluent foci of formation of abscesses with lymphocytic and polymorphonuclear infiltrate, fibrin and necrosis.
Around the inflammatory foci, the hepatic parenchyma was disintegrated, fibrinous, without giant cells.
Gram and G stainings were negative and Kinesin staining was positive.
In the microbiological study, Ziehl Nielsen stain was positive (++).
The current culture was negative and the tissue sample for Mycobacterium culture was incubated.
An atypical Mycobacterium tuberculosis or nodular Mycobacterium tuberculosis was diagnosed.
The study was complemented with a red background, smear of gastric content and sputum and bacilloscopy, culture and PCR for Mycobacterium complex of bronchoalveolar lavage, as well as hemocultives for Mycobacterium.
According to the diagnostic hypothesis of M. tuberculosis infection, the patient was diagnosed from a room with high efficiency air filter (HEPA) and positive pressure, to an isolation with HEPA filter and negative pressure.
Immunosuppression was discontinued and treatment with isoniazid, rifampicin, pyrazinamide and etambucil was initiated.
Awaiting microbiological identification, and in case of doubt of an infection with M. tuberculosis or atypical Mycobacterium, moxifloxacin and clarithromycin were associated.
A study of contact with the family group was carried out according to the recommendation of the bronchopulmonary team, resulting negative.
A rounded lesion was observed in the eye fundus, located underneath the macula, not overlying, bilateral.
Sputum smears of gastric content and tracheal aspirate were positive (+) and also bronchial fluid obtained by BAL (++).
Urine smear and CSF were negative.
The culture sent to the Instituto de Salud Pública de Chile confirmed the presence of M. tuberculosis in gastric contents, sputum, BAL and tissue, rifampicin, isoniazid, streptomycin, and hepatic mutations susceptible to growth hormone β -agonist.
Blood cultures for Mycobacterium spp. were negative.
1.
After microbiological confirmation, treatment was adjusted to four drugs (isoniazide, rifampicin, pyrazinamide, and etambucil).
Upon completing one month of treatment, the patient was afflicted with poor general condition and well tolerated therapy.
Control smears were negative, CT scan of the brain, paranasal sinuses, chest and pelvis showed no lesions, and CT scan of the abdomen showed significant regression of nodular liver lesions.
The patient completed two months of daily treatment (day +112 post-HSCT), after which the treatment was adjusted to the triweekly isoniazid, rifampicin and ethambutaline therapy.
Controlled by the transplant, infectious and bronchopulmonary team, the patient presented good general conditions, with images showing resolution of the hepatic and pulmonary involvement, maintaining negative sputum smears.
It completed 11 months of antimicrobial treatment.
Two years after the transplant, the patient was immunoreconstected, with no evidence of tuberculosis infection reactivation.
