Blood, 1 December 2001, Vol. 98, No. 12, pp. 3496-3497
CORRESPONDENCE
To the editor:
Traumatic lumbar puncture at diagnosis and outcome in
childhood acute lymphoblastic leukemia
The recent report by Gajjar et al1 demonstrates
impressively the adverse effect of a traumatic lumbar puncture (defined as more than 10 red blood cells per microliter of cerebrospinal fluid
[CSF]) at the time of diagnosis on treatment outcome of children with
acute lymphoblastic leukemia (ALL). The inferior prognosis can be
predominantly observed in a subgroup of patients with 2 consecutive
traumatic lumbar punctures and the detection of leukemic cells in the
CSF. The authors conclude that the iatrogenic introduction
of leukemic cells into the CSF may be one reason for the
reduced outcome.
In the treatment protocols XI2 and XII3 of
the St Judes Children's Research Hospital, the patients received the
first intrathecal therapy with methotrexate, hydrocortisone, and
cytarabine at day 2. Thus they had a period of at least 24 hours
without sufficient central nervous system (CNS)-directed treatment. In contrast, in ALL-Berlin-Frankfurt-Munich (BFM) frontline
protocols, the first intrathecal methothrexate is immediately
administered during the diagnostic lumbar puncture. Consecutive lumbar
punctures (at diagnosis and for CNS-directed treatment), which may
increase the risk of contamination of the CSF with blast cells, are not necessary. Furthermore, Gajjar et al's data show a
surprisingly high percentage of traumatic punctures (21%), in more
than half of the cases with detection of leukemic blasts in the CSF
after cytocentrifugation.1
From 88 children with initial ALL treated in our institution between
November 1995 and January 2001, 56 CSF preparations of the diagnostic
lumbar puncture had been preserved and the CNS status could be
reevaluated. A traumatic lumbar puncture according to the above
classification groups occurred in 4 out of 56 cases (7%), and in only
1 sample could 1 single leukemic cell be observed. Hitherto, 5 children
suffered a leukemic relapse (3 isolated and 2 combined bone
marrow/testis relapses). No CNS relapse occurred within this group.
These data emphasize the importance of a properly performed lumbar
puncture particularly at time point of diagnosis when higher numbers of
blast cells are circulating in the peripheral blood. Diagnostic lumbar
punctures should only be done by an experienced physician. Furthermore,
early administration of CNS-directed therapy might help to reduce the
risk of blast cell microdissemination in the case of iatrogenic
inoculation of blood during the procedure.
Christian Kebelmann-Betzing, Karlheinz Seeger, Renate Wolf, and Günter Henze
Correspondence: Günter Henze, Charité Medical
Center, Humboldt University, Department of Pediatric
Oncology/Hematology, Berlin, Germany
References
1.
Gajjar A, Harrison PL, Sandlund JT, et al.
Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia.
Blood.
2000;96:3381-3384[Abstract/Free Full Text].
2.
Rivera GK, Raimondi SC, Hancock ML, et al.
Improved outcome in childhood acute lymphoblastic leukemia with reinforced early treatment and rotational combination chemotherapy.
Lancet.
1991;337:61-66[CrossRef][Medline]
[Order article via Infotrieve].
3.
Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui C-H.
Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia.
N Engl J Med.
1998;338:499-505[Abstract/Free Full Text].
Response:
Traumatic lumbar puncture at diagnosis of childhood
acute lymphoblastic leukemia
We agree with the recommendations of Kebelmann-Betzing et
al that initial lumbar puncture should be performed by an experienced clinician and followed immediately by intrathecal therapy. As also
stated in our article,1 we now routinely perform this procedure with patients under short-acting general anesthesia. When the
diagnosis of leukemia is uncertain because of the lack of circulating
leukemic cells, we postpone lumbar puncture and intrathecal therapy
until the diagnosis is established by bone marrow examination.
It is difficult to compare the frequency of traumatic lumbar
puncture in the series of Kebelmann-Betzing et al with that of ours
because the status of their patients was determined retrospectively on
the basis of "preserved" cerebrospinal fluid; in contrast, we used
fresh samples of cerebrospinal fluid. The integrity of the erythrocytes
and the morphology of the leukocytes are expected to be altered in
preserved samples. Since we first implemented steps to reduce this
iatrogenic complication, we have substantially reduced the frequency of
traumatic lumbar punctures with blast cells from 11% to 5% and that
of traumatic lumbar punctures without blast cells from 10% to 7%. It
should be noted that we stringently define traumatic lumbar puncture as
at least 10 erythrocytes per microliter.
As shown by Total Therapy Study XIII,2 early
intensive intrathecal and systemic therapy is now more successful in
treating and preventing central nervous system (CNS) leukemia, even in patients whose leukemic blast cells are iatrogenically introduced into
the cerebrospinal fluid by traumatic lumbar puncture.
Therefore, cranial irradiation is seldom necessary in contemporary
treatment programs. But others have reported neuropsychologic deficits
in children who received CNS-directed therapy consisting solely of approximately 20 intrathecal treatments of methotrexate,
hydrocortisone, and cytarabine over 3 years.3 The
challenge now is to optimize intrathecal and systemic therapy to
maximize efficacy and minimize toxicity. Developing appropriate
measures to avoid traumatic lumbar puncture and hence the need of extra
intrathecal therapy is but one step toward this goal.
Amar Gajjar and Ching-Hon Pui
Correspondence: Amar Gajjar, Department of
Hematology-Oncology, Rm 6024, St Jude Children's Research Hospital,
332 N Lauderdale, Memphis, TN 38105
References
1.
Gajjar A, Harrison PL, Sandlund JT, et al.
Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia.
Blood.
2000;96:3381-3384.
2.
Pui C-H, Mahmoud HH, Rivera GK, et al.
Early intensification of intrathecal chemotherapy virtually eliminates central nervous system relapse in children with acute lymphoblastic leukemia.
Blood.
1998;92:411-415[Abstract/Free Full Text].
3.
Hill DE, Ciesielski KT, Sethre-Hofstad L, Duncan MH, Lorenzi M.
Visual and verbal short-term memory deficits in childhood leukemia survivors after intrathecal chemotherapy.
J Pediatr Psychol.
1997;22:861-870[Abstract/Free Full Text].
