12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
0215
TUBERCULOSIS (TBC) FOLLOWING SINGLE-UNIT MYELOABLATIVE UMBILICAL CORD-
BLOOD TRANSPLANTATION (UCBT) FOR ADULTS WITH HEMATOLOGICAL MALIGNANCIES
S. Cantero, I. Jarque, G. Sanz, M. Salavert, I. Lorenzo, G. Martin,
A. Sempere, P. Montesinos, J. Sanz, L. Algarra, J. Moscardo, R. Renart,
F. Gomis, G. Orti, M.A. Sanz
Hospital La Fe, VALENCIA, Spain
Introduction. Allogeneic hematopoietic stem cell transplantation (allo-
SCT) recipients, especially those receiving UCBT, are prone to serious
infections, including TBC. Incidence rates of TBC after allo-SCT in several
case series vary from less than 0.1 to 5.5%. However, only one
study has been published on TBC after UCBT. Patients and Methods.
Medical records of 106 adult patients with hematological malignancies
who underwent single-unit UCBT with a myeloablative conditioning at
our institution from May 1997 to December 2006 were retrospectively
reviewed for the diagnosis of TBC. Conditioning regimen included
thiotepa, busulfan (oral, 43; iv, 63' iv single daily dose, 34), cyclophosphamide
(72) or fludarabine (34), and antithymocyte globulin (Lymphoglobulin,
32; Thymoglobulin, 74). All received cyclosporine plus
prednisone for graft-versus-host disease (GVHD) prophylaxis and filgrastim
to fasten engraftment. Diagnoses were acute lymphoblastic
leukemia (ALL) in 37, acute myeloblastic leukemia (AML) in 30, chronic
myelogenous leukemia (CML) in 22, myelodysplastic syndrome
(MDS) in 9 and other lymphoid malignancies in 8. No patient had personal
or family history of TBC prior to UCBT. The pretransplant evaluation
of the respiratory system included chest radiographs and pulmonary
function tests that were normal in all patients. Sputum smears
and cultures for acid-fast bacilli were not routinely obtained. A diagnosis
of TBC was based on the identification of M. tuberculosis in at least
one fluid or tissue specimen (sputum, bronchoalveolar lavage, pleural fluid,
lymph node). Results. Median age and weight were 31 yr (range, 15-
49) and 71 kg (range, 41-112). HLA match (HLA-A and -B at antigen and
-DRB1 at allelic level) was 6/6 in 6 (6%), 5/6 in 39 (37%), and 4/6 in 61
cases (57%). The median number of nucleated cells and CD34 + cells
infused was 2.1×107 /kg and 1×105 /kg respectively. Median time to neutrophils
> 0.5×109 /L was 22 days (range, 11-57). Mycobacterium tuberculosis
infections were diagnosed in six of the 106 patients (5%). They
had no different risk factors for TBC compared with the other 100
patients. Their detailed clinical characteristics are shown in Table 1.
Patient #1 had a Mycobacterium kansasii infection 6 months before
TBC. Patients were scheduled to receive antituberculous treatment
according to drug susceptibility patterns for at least 6 months. Patients
#2, #5, and #6 died of disseminated TBC. Conclusions. TBC is an infrequent
but severe infection after allo-SCT, and is associated with high
mortality, especially when occurring within 3 months of transplantation.
It can also complicate post-transplant management as antituberculosis
drugs frequently interfere with immunosuppressive therapy and they
may narrow therapeutic ranges. T-cell recovery is one of the most important
factors for curing TBC infection. Shortening the diagnostic delay
could also have a pivotal impact on survival. Transplantation centers
should maintain a high level of suspicion for TBC in patients receiving
UCBT. Screening before UCBT with PPD skin test or other tests should
be performed in these patients.
Table 1.
78 | haematologica/the hematology journal | 2007; 92(s1)
0216
PALIVIZUMAB TREATMENT OF RESPIRATORY SYNCYTIAL VIRUS INFECTION AFTER
ALLOGENEIC STEM CELL TRANSPLANTATION
F. Sicre, M. Robin, R. Peffault de Latour, R. Porcher, C. Scieux,
C. Ferry, V. Rocha, K. Boudjedir, A. Devergie, A. Bergeron,
A. Gluckman, E. Azoulay, J. Lapalu, G. Socie, P. Ribaud
Saint Louis Hospital, PARIS, France
Respiratory syncytial virus (RSV) infections after HSCT can lead to
severe respiratory failure and is associated with a fatal issue in a substantial
number of patients (pts). Since palivizumab (P) has been shown to
be efficient to lower RSV infection related hospitalization in high risk
infant, P has been used in an uncontrolled manner to treat RSV infections
in HSCT recipients, including in our transplant unit, with no clear knowledge
of its impact on outcome. This study was conducted to determine
outcome in HSCT recipients diagnosed with RSV infection and to estimate
P impact, if any, on mortality. From January 1999 to March 2006,
all pts with RSV infections after HSCT at Saint- Louis Hospital were retrospectively
reviewed in order to determine cumulative incidence of
RSV-related death, risk factors for 4-month transplant-related-mortality
post RSV diagnosis (early TRM), and eventual impact of P. Forty pts
with RSV infections were identified (median age : 16 years - range 3 to
65), at a median interval from transplant to RSV diagnosis of 90 days (d)
(range: -15 d to 987 d ). 24 pts had received an unrelated stem cell graft.
Characteristics at diagnosis were: pneumonia in 16, bronchitis or bronchiolitis
in 8 and upper respiratory disease in 16 pts; 16 pts had hypoxemia.
Among them, 18 received P at diagnosis (15 mg/kg - intravenous
course - 1 to 3 monthly injections. Pts treated with P were significantly
younger, have received more cord blood transplant, had lower neutrophil
and lymphocyte counts, and a shorter interval between transplantation
and infection. One-year overall survival was 75% (95% CI:
63-91), corresponding to 77% (95% CI: 60-99) and 75% (95% CI: 59-
97) for palivizumab-treated and -untreated patients, respectively. P did
not shorten RSV excretion or significantly prevent progression from
upper to lower respiratory tract infection Only one patient (treated with
P) died from RSV pneumonia alone, giving a 2.6% cumulative incidence
of RSV-related death (95% confidence interval (CI): 0-7.7). Seven other
pts died during the 4 months following RSV diagnosis. All of them died
from respiratory failure of multiple causes (RSV +: n = 4; RSV-: n = 3).
Four-month non-relapse mortality was 16% (95% CI: 17-27): 23% (95%
CI: 0-50) and 9% (95% CI: 0-22) of patients treated with or without P,
respectively. In a multivariate Cox model, the only risk factors for 4month
non-relapse mortality were stem cell source (unrelated cord
blood, hazards ratio (HR): 4.9, 95% CI: 1.1-22, p=0.039; and oxygen
required at RSV diagnosis (HR: 7.31, 95% CI: 1.8-49, p=0.012). In conclusion
this study doesn’t support the use of P as an RSV curative therapy
after HSCT. Because P was predominantly used in pts with classical
poorer prognosis, we cannot robustly test its impact; nevertheless
classical poorer prognosis factor were not found to be significant in this
study. Given the high cost of palivizumab therapy and the arrival of
several new compounds, our findings do not support further use of this
drug in an uncontrolled manner.