Acute Leukemias - Republican Scientific Medical Library

276 Chapter 22 · Relapsed Acute Lymphoblastic Leukemia
An example of the type of regimen that reiterates the
initial treatment program was the report by Koller et al.
using “hyper-CVAD.” This regimen is patterned after
the style of therapy developed to treat Burkitt’s lymphoma/leukemia
and utilizes fractionated cyclophosphamide,
high-dose cytarabine, and high-dose methotrexate
[6]. Sixty-six adults with relapsed ALL received this
regimen consisting of eight courses of alternating chemotherapy
with growth factor support followed by oral
maintenance chemotherapy. The authors reported a frequency
of CR of 44% with a median survival of approximately
8 months. Three-year survival was poor at approximately
10%.
High-dose cytarabine has been used alone and in
combination with a number of different agents. In combination
with L-asparaginase [2–4], doxorubicin [5],
idarubicin [7, 8], or mitoxantrone [9–12], CRs as high
as 72% have been reported in relapsed patients with
ALL. Issues of patient mix make it difficult to assess if
a specific regimen is superior to others, but in general
a combination of high-dose cytarabine and an anthracycline
has the greatest likelihood of achieving a second
CR in relapsed patients (or a first CR in refractory patients).
The toxicity of these regimens should be balanced
against the benefits of achieving a CR. An example
of such a regimen is the combination of high-dose
cytarabine with a single high dose of idarubicin. We reported
that this active regimen produced CRs in 44% of
patients [13, 14].
However, second CRs are notoriously difficult to
maintain and typically each succeeding response (if
one can be achieved) is briefer than the preceding
one. In general, patients with a suitable allogeneic transplant
option should be referred for such a transplant in
second CR.
22.2 Bone Marrow Transplant in Adult Acute
Lymphoblastic Leukemia
Human leukocyte antigen- (HLA) matched identical
sibling bone marrow transplants have been used in
adults with ALL in a variety of settings. This dose-intense
treatment has the ability to eradicate leukemia
in a small subset of patients with disease refractory to
conventional chemotherapy. In general, there are three
main prerequisites for performing an allogeneic transplant.
The patient must be in acceptable physical condition
to withstand the rigors of the transplant. Secondly,
the disease should be in a minimal disease state (preferably
complete remission) to reduce the risk of relapse
posttransplant. Finally, a suitable donor must be identified.
HLA typing should be performed on the patient
and the patients’ immediate family at the time of diagnosis.
Early HLA typing is preferred because this typing
may take up to 2 weeks to complete and if deferred until
relapse, unwanted delays in identifying a donor may occur.
If a suitable related donor is not identified, we recommend
no further testing until a transplant is recommended.
At that time extended family members may be
typed, but in addition, a preliminary search of unrelated
donors should be initiated. This initial search through
the National Marrow Donor Registry is performed free
of charge to the patient. This is a one-time search of
over ten million adult donors and more than 190 000
cord blood units to help identify potential candidates.
In addition to the preliminary domestic search, an international
search may also be initiated depending on the
patient‘s racial and ethnic background. If a potential donor
is identified, additional testing will be necessary,
and this is known as the “formal” search. Once an unrelated
donor is identified, logistical planning for the
transplant can begin.
However, the lack of availability of HLA-matched
donors and the toxicity and mortality seen with transplant
often limits the utility of this approach. Davies
et al. [15] studied the outcome of 115 consecutive patients
with recurrent ALL over a 2-year period from
1991–1993. A matched, related donor was identified in
35% of which 75% made it to transplant (26% of the
original cohort). Of the 75 patients without a related donor,
58 patients had an unrelated donor search initiated.
An unrelated donor was identified for 22 (37%) of those
whom a search was performed and 15 of these patients
proceeded to a matched, unrelated donor transplant
[15]. Fortunately, the likelihood of finding a suitable
matched, unrelated donor has improved; however, there
are still some patients for whom a suitable donor cannot
be identified.
Unfortunately allogeneic transplant is not a panacea
for treating relapsed ALL. In part, the limits of transplant
can be seen by reviewing patterns of failure. Patterns
of failure with allogeneic transplant in ALL are
dissimilar to that of patients transplanted for AML. In
AML, patients treated with allogeneic transplant often
fail therapy because of treatment-related mortality (infectious
complications, GVHD, etc.). In contrast, patients
with ALL who undergo allogeneic transplant suf-