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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 91 No. 3 (February 1), 1998:
pp. 1083-1090
T-Cell-Depleted Allogeneic Bone Marrow Transplantation as
Postremission Therapy for Acute Myelogenous Leukemia: Freedom From
Relapse in the Absence of Graft-Versus-Host Disease
By
Esperanza B. Papadopoulos,
Matthew H. Carabasi,
Hugo Castro-Malaspina,
Barrett H. Childs,
Stephen Mackinnon,
Farid Boulad,
Alfred P. Gillio,
Nancy A. Kernan,
Trudy N. Small,
Paul Szabolcs,
Joanne Taylor,
Joachim Yahalom,
Nancy H. Collins,
Sharon
A. Bleau,
Patricia M. Black,
Glenn Heller,
Richard J. O' Reilly, and
James W. Young
From the Allogeneic Bone Marrow Transplantation Service, Division of
Hematologic Oncology, Department of Medicine; the Department of
Pediatrics; the Department of Nursing; the Department of Radiation
Oncology; the Department of Biostatistics and Epidemiology, Memorial
Sloan-Kettering Cancer Center, Cornell University Medical College, New
York; and The Laboratory of Cellular Physiology and Immunology, The
Rockefeller University, New York, NY.
 |
ABSTRACT |
Thirty-one consecutive patients with acute myelogenous leukemia
(AML) in first complete remission and 8 with AML in second complete
remission received T cell-depleted allogeneic bone marrow transplants
from HLA-identical sibling donors. Patients received myeloablative
cytoreduction consisting of hyperfractionated total body irradiation,
thiotepa, and cyclophosphamide. Those patients at risk for
immune-mediated graft rejection received additional immune suppression
with antithymocyte globulin and methylprednisolone in the early
peritransplant period. Patients with AML who underwent allogeneic
T-cell-depleted bone marrow transplantations (BMT) in first or second
remission have achieved respective disease-free survival (DFS)
probabilities of 77% (median follow-up at approximately 56 months) and
50% (median follow-up at approximately 48 months). Ten of 31 patients
transplanted in first remission were  40 years old and have attained
a DFS at 4 years of 70%. For patients with AML transplanted in first
or second remission, the respective cause-specific probabilities of
relapse were 3.2% or 12.5%, and those of nonleukemic mortality were
19.4% or 37.5%. There were no cases of immune-mediated graft
rejection and no cases of grade II to IV acute graft-versus-host
disease (GVHD). All survivors enjoy Karnofsky performance scores (KPS)
of 100%, except 2 patients with KPS of 80% to 90%.
T-cell-depleted allogeneic BMT can provide durable DFS together with
an excellent performance status in the majority of patients with de
novo AML. In addition, GVHD is not an obligatory correlate of the
graft-versus-leukemia benefit or freedom from relapse afforded by
allogeneic BMT administered as postremission therapy for AML. This
study provides a basis for prospective comparison with other
postremission therapies considered standard in the management of
patients with this disease.
| |
INTRODUCTION |
THE MAJORITY of adults with de novo acute
myelogenous leukemia (AML) achieve remission after initial induction
with cytarabine and an anthracycline.1,2 Unfortunately,
most of these patients relapse. Postremission treatment options
designed to ensure long-term disease-free survival (DFS) include
chemotherapy alone, high-dose chemotherapy with autologous stem cell
rescue, or allogeneic bone marrow transplantation (BMT). Although the
relative merits of these approaches continue to be debated and are the
subjects of other comparative trials, recipients of allogeneic bone
marrow transplants have consistently shown reductions in the risk of relapse.3-12 The greater curative potential of an
allogeneic BMT has often been mitigated, however, by the risks of
transplant-associated morbidity and mortality, particularly those
caused by graft-versus-host disease (GVHD) and its complications. This
is especially true in older patients, who constitute the majority of
patients with AML.
In an earlier study we examined the efficacy of allogeneic bone marrow
transplants, depleted of T cells by lectin agglutination and sheep
erythrocyte rosetting, as postremission therapy in patients with AML in
first remission.8 Although that study showed an almost
complete elimination of acute and chronic GVHD without compromising the
antileukemic efficacy of the allograft, immune-mediated graft rejection
was a significant cause of treatment failure. As a consequence, the
3-year DFS was 45%. The pretransplant cytoreductive regimen and
peritransplant supportive care were therefore modified to reduce or
eliminate the incidence of graft failure and immune rejection, without
increasing regimen-related toxicity. These modifications included the
introduction of thiotepa between total body irradiation and
cyclophosphamide, based on murine studies13 and clinical
data14,15 that had shown the engraftment-potentiating, myeloablative, and immunosuppressive activity of thiotepa.
Antithymocyte globulin and steroids were also added to the
peritransplant regimen to prevent immune-mediated rejection caused by
residual host T cells.16-18 We now report the results of
T-cell-depleted allogeneic bone marrow transplants using this regimen
for 31 consecutive patients with AML in first remission and 8 in second
remission who have achieved a median follow-up duration of
approximately 4.8 years and 4 years, respectively.
| |
MATERIALS AND METHODS |
Patient characteristics.
Thirty-one consecutive patients with primary AML in first remission and
8 consecutive patients in second remission underwent a
T-cell-depleted, allogeneic bone marrow transplant during the period
of October 31, 1991 to October 12, 1995 and were analyzed as of August 1, 1997. This trial was conducted in accordance with an
Institutional Review Board-approved clinical research protocol. Eligibility criteria for enrollment and analysis in this study included
a diagnosis of AML in first or second remission, in the absence of a
preexisting myelodysplastic syndrome or treatment-related secondary
leukemia; age less than 55 years; availability of an HLA-identical
related donor; absence of active infection; and lack of coexisting
cardiac, hepatic, or renal dysfunction that would preclude
administration of the cytoreductive regimen. Patients who were
seropositive for hepatitis A, B, or C were not excluded unless there
was coexisting active hepatitis. HLA matching was established by
serological identity for HLA-A, HLA-B, and HLA-DR loci, and where
indicated by isoelectric focusing for subtype matching at the A and B
loci and by DNA sequence-specific oligonucleotide typing for HLA-DR.
Details of the patient characteristics before transplant are presented
in Table 1. Of the 31 patients with AML in
first complete remission (CR), the median age was 36.7 years; 10 patients (32%) were 40 years old at the time of
transplant. Eight of the 31 patients with AML in first CR required two
inductions to achieve remission, and 9 had karyotypes at diagnosis that
have now been associated with favorable prognoses after chemotherapy alone.10,19 No patient received high-dose cytarabine during induction, and only 9 (13%) patients received high-dose cytarabine during consolidation.
Preparative regimen.
All patients received myeloablative cytoreduction consisting of
hyperfractionated total body irradiation (HFTBI) followed by thiotepa
and high-dose cyclophosphamide. HFTBI was administered in fractions of
125 cGy at a dose rate of 8 to 20 cGy/min, three fractions per day, at
5- to 7-hour intervals for 4 days, to a total dose of 1,500 cGy. All
patients had protective lung shielding to reduce the effective dose to
the lung parenchyma to approximately 800 to 900 cGy. Overlying ribs
received an additional 600 cGy boost using high-energy electrons to
increase the total dose to the chest wall to approximately 1,500 cGy.
Male patients received an additional 400 cGy testicular boost with
electrons in a single fraction on the first day of HFTBI.20
After completion of HFTBI, thiotepa 5 mg/kg/dose was administered over
4 hours on each of 2 consecutive days, with no adjustment for obesity.
This was followed by high-dose cyclophosphamide 60 mg/kg/dose on each
of 2 consecutive days. Cyclophosphamide was dosed according to the
lesser of actual or ideal body weight. In patients whose actual weight
exceeded ideal body weight by more than 25%, an adjusted ideal body
weight was used (adjusted ideal body weight = [{actual total body
weight  ideal body weight} × 40%] +[ideal body
weight]).
Bone marrow collection, T-cell-depletion, and transplantation.
Normal bone marrow was aspirated from the iliac crests under general
anesthesia. T cells were removed from the bone marrow by sequential
soybean lectin agglutination (SBA) and sheep red blood cell
(sRBC)-rosette depletion.8,21 This method achieves a 2.8- to 3-log10 depletion of clonable T
lymphocytes.22 Marrow was infused through central venous
access 24 to 48 hours after the completion of high-dose
cyclophosphamide.
Rejection prophylaxis.
Published analyses from this institution have shown that all patients
aged 30 years or older, and any aged recipient of a male donor graft,
are at risk for immune-mediated graft failure after T-cell-depleted
allogeneic BMT.16,17 These patients therefore received
antithymocyte globulin (ATG) and methylprednisolone for graft rejection
prophylaxis. Of the 31 first remission patients, 21 received ATG at a
dose of 30 mg/kg/d and methylprednisolone 2 mg/kg/d on days 5
and 4; 5 patients received ATG 15 mg/kg every other day from day
+5 through day +13 along with methylprednisolone 2 mg/kg/d until day
+13 followed by a rapid taper over the ensuing 14 days; 3 patients
received steroids alone posttransplant because of anaphylactic
reactions to ATG; and 2 patients required no graft rejection
prophylaxis. Among the 8 second remission patients, 3 patients did not
require prophylaxis; 2 patients received two doses of ATG and
methylprednisolone as above on days 5 and 4; and 3 patients received ATG and methylprednisolone beginning day +5, as
above.
GVHD prophylaxis.
No additional prophylaxis against GVHD was administered.
GVHD evaluation and management.
GVHD was diagnosed clinically, confirmed pathologically by skin or
mucosal biopsy, and classified according to standard
critieria.23,24 Only patients who engrafted and survived
30 days were evaluable for acute GVHD, unless it had already been
diagnosed before a terminal event. Patients who developed acute GVHD
were treated with either topical steroids or methylprednisolone 2 mg/kg/d. Patients surviving 100 days or longer were evaluable for
chronic GVHD.
Supportive care.
All patients were hospitalized in single rooms with filtered air and
reverse isolation. Standard prophylaxis against opportunistic infections included sulfamethoxazole/trimethoprim prophylaxis against
Pneumocystis carinii pneumonia (PCP) pretransplant. Those patients who had received ATG and steroids as rejection prophylaxis were given aerosolized pentamidine after transplant to prevent PCP.
Once stable engraftment was achieved with a platelet count 100,000,
all patients resumed prophylaxis with sulfamethoxazole/trimethoprim prophylaxis. Acyclovir was administered as prophylaxis against DNA
herpesvirus infections. All cytomegalovirus (CMV)-seronegative patients received CMV-seronegative blood products regardless of the CMV
serological status of the marrow donor. Ten of 31 first remission
patients and 6 of 8 second remission patients received fluconazole
antifungal prophylaxis. Prophylactic antibacterials were not used. Of
the 39 total patients, 16 (11/31 transplanted in first CR and 5/8
transplanted in second CR) received granulocyte colony-stimulating
factor (G-CSF) in the early posttransplant period; representative
clinical indications included BMT donor cell dose <2 × 107 mononuclear cells (MNC)/kg of recipient weight or
persistent fever or infection despite appropriate antibiotics. No other
cytokines were administered.
Engraftment and donor chimerism.
Myeloid engraftment was defined as an absolute neutrophil count (ANC)
500/µL on 3 consecutive days posttransplant. Platelet engraftment was defined as an untransfused platelet count of
20,000/µL for at least 3 consecutive days. Bone marrow aspirates
were obtained at regular intervals posttransplant to assess cellularity
and presence or absence of leukemic cells. Donor chimerism was assessed in sex-mismatched donor-recipient pairs by metaphase karyotype analyses
or fluorescent in situ hybridization (FISH) of the X and Y chromosomes
in interphase cells; restriction fragment length DNA polymorphisms
(RFLP) were compared in sex-matched pairs.
Data collection and statistical methods.
Analyses were performed as of August 1, 1997. DFS was
defined as the interval from BMT to death, relapse, or last follow-up, and was estimated using the method of Kaplan-Meier.25
Estimates of the probability of relapse and nonleukemic mortality were
calculated after adjustments for the competing risks of treatment
failure.25
| |
RESULTS |
Engraftment and donor chimerism.
The median cell dose of the infused marrow (SBA-negative,
sRBC-rosette-negative fraction) was 2.77 × 107
nucleated cells/kg of recipient weight (range 0.69 to 7.44). All 31 patients with AML in first CR and all 8 patients with AML in second CR
achieved primary engraftment, with complete donor chimerism. This has
been maintained in all survivors, except 1 patient transplanted in
first CR who has evidenced mixed chimerism (approximately 50:50 by
RFLP) in the bone marrow without relapse, now 5.5 years status
post-BMT; this patient did not have a favorable karyotpe10,19 at diagnosis. Three additional patients,
among 14 recipients of sex-mismatched allografts whose interphase cells could be analyzed by FISH, have sustained mixed chimerism with 30% to
50% host cells in the peripheral blood mononuclear fraction, despite
full donor chimerism in the bone marrow. The two relapses in this
series, however, were not predicted by antecedent mixed host/donor
chimerism.
There were no episodes of immune-mediated graft rejection as reported
in the previous series from this institution.8,16,17 Patients with AML in first CR achieved stable myeloid engraftment by
day +13 (median, range 11 to 19 days). Platelet engraftment occurred by
day +24 (median, range 12 to 93 days). Comparable engraftment
parameters characterized the patients transplanted with AML in second
CR. These data are summarized in Table 2.
One patient with AML in first CR experienced late graft failure
associated with CMV infection and its treatment. Analysis of lymphoid
elements confirmed persistent donor chimerism. This patient received
secondary infusions of T-cell-depleted marrow and peripheral blood
progenitors from the primary donor. These secondary infusions were
administered without cytoreduction and have resulted in sustained
trilineage donor engraftment.
DFS and relapse.
The estimated probability of DFS at 4 years for patients with AML
transplanted in first remission is 77.4% (SE = 7.5%), with a median
follow-up of 56.2 months (Fig 1A). For
patients transplanted in second remission, the DFS probability estimate
at 3 years is 50.0% (SE = 18%), with a median follow-up of 47.5 months (Fig 1A).
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| Fig 1.
Kaplan-Meier estimates of probability of DFS for patients
transplanted with T-cell-depleted allografts for AML. (A) Patients with AML transplanted in first CR compared with those transplanted in
second CR. (B) Patients with AML transplanted in first CR, analyzed
according to age at time of BMT; P value was not significant.
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As shown in Fig 1B, the probability of 4-year DFS for patients with
primary AML transplanted in first remission under the age of 40 years
is 81%; older patients, ranging in age from 40 to 51.5 years, have
achieved a 4-year DFS probability of 70% (P = .52). Comparison
of the 23 patients who achieved a first CR after a single induction
with the 8 patients who required two induction courses also reveals no
significant differences in 4-year DFS probabilities (one induction
course, 73.9%; two induction courses, 87.5%; P =.45; data not
shown). Furthermore, when the overall group is segregated into "good
risk" karyotypes [n = 9, t(8;21) in 7 patients and 1 each with
t(15;17) or inv(16)] versus all other karyotypes (n = 22), the 4-year
DFS probability estimates are the same (77.8% and 77.3%,
respectively; data not shown). The inclusion of patients with good risk
karyotypes therefore did not favorably influence the overall results.
Twenty-three of 24 long-term survivors transplanted in first remission
and 3 of 4 long-term survivors transplanted in second remission enjoy
Karnofsky performance scores of 100%. The other 2 patients have
performance scores of 80% and 90%. One, transplanted in first CR, had
prolonged delay in hematopoietic reconstitution but is now durably
engrafted. The other, transplanted in second remission, has compensated
but fixed neurological deficits that antedated and were independent of
the transplant.
Only 2 patients in the entire series have relapsed to date. Both were
over 50 years old. The sole patient who relapsed after transplantation
in first remission had AML FAB-M4 with trisomy 8. The single patient
who relapsed after transplantation in second remission had AML FAB-M3
with t(15;17). The cause-specific probability of relapse, controlling
for the competing risks of treatment failure caused by nonleukemic
causes, is 3.2% (SE = 6%) at 4 years for patients transplanted in
first remission and 12.5% (SE = 20%) at 3 years for those
transplanted in second remission (Fig 2A).
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| Fig 2.
(A) Cause-specific probability of relapse, controlling
for the competing risks of treatment failure by nonleukemic causes, among patients with AML transplanted in first or second CR. (B) Cause-specific probability of death, adjusting for the competing risk
of leukemic relapse, among patients with AML transplanted in first or
second CR. For patients with AML in first CR, the cause-specific
probability of regimen-related mortality in the first 100 days after
transplant is 9.7% ± 5%.
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Posttransplant Epstein-Barr virus lymphoproliferative disorders
(EBV-LPD).
Three of the 31 patients transplanted with AML in first CR developed
posttransplant EBV-LPD.26 Two of these were treated with
donor leukocytes and resolved. One of these 2 patients developed chronic GVHD secondary to the donor leukocyte infusion and subsequenly died (see below). The third patient had EBV-LPD limited to the tonsils,
but had no evidence of additional disease after primary excisional
biopsy and was not treated with donor leukocytes. None of the 8 patients transplanted in second CR developed EBV-LPD.
GVHD.
All patients were evaluable for acute GVHD. Two patients transplanted
in first remission developed grade I acute GVHD involving only the
skin. One was treated with topical corticosteroids, and the other was
treated with a brief course of systemic methylprednisolone, both with
complete resolution and without recurrence upon cessation of therapy.
None of the 8 patients transplanted in second remission developed acute
GVHD. Thus, the incidence of grade I GVHD in the entire group was
approximately 5%; grades II to IV GVHD were not observed.
Thirty-five patients (28 in first CR, 7 in second CR) were evaluable
for chronic GVHD. Of these, only 1 patient transplanted in first CR
developed de novo extensive chronic GVHD involving the skin, liver, and
oral mucosa. The incidence of chronic GVHD solely attributable to the
T-cell-depleted marrow graft is therefore approximately 3%. One
additional patient developed an EBV-LPD 127 days posttransplant in
first CR. This patient developed chronic GVHD involving the oral mucosa
after receiving unirradiated donor-derived leukocytes containing 1 × 106 CD3+ cells/kg26 (also
see below).
Causes of death.
The causes of treatment failure and other outcome parameters are
summarized in Table 2. Of the 31 patients transplanted with AML in
first remission, 7 have died. Three patients died at 39, 43, and 49 days posttransplant as a result of fungal pneumonia, hepatic
venoocclusive disease complicated by CMV pneumonia, and CMV pneumonia
alone, respectively. One patient died late posttransplant (15.8 months)
of an interstitial pneumonitis; on open lung biopsy, no cause could be
established. The patient successfully treated for an EBV-LPD with donor
leukocytes, who subsequently developed chronic GVHD as noted above,
later died of sepsis 19.8 months after transplant. The single patient
who developed de novo extensive chronic GVHD succumbed to fungal
pneumonia complicating chronic immunosuppressive therapy. One patient
with trisomy 8 at diagnosis relapsed at 3.5 months posttransplant and
subsequently died of her disease. For patients transplanted in first
remission, the cause-specific probability of regimen-related mortality,
adjusted for the competing risk of leukemic relapse, is 9.7% (SE = 5%) at 100 days (Fig 2B). The cause-specific probability of death by
all causes other than leukemic relapse is 19.4% (SE = 8%) overall (Fig 2B).
Of the 8 patients transplanted with AML in second remission, 4 died.
Three of these deaths were caused by infectious complications (Table
2). One patient relapsed 3 years after transplant. The cause-specific
probability of nonleukemic mortality in this group is 12.5% (SE = 12%) at 100 days and 37.5% (SE = 18%) overall in this group.
There were no cases of immune-mediated graft failure in the entire
group of first and second remission patients. This conclusion is based
on the absence of features indicative of immune rejection of donor
grafts previously published from this institution.16,17
| |
DISCUSSION |
Thirty-one consecutive patients undergoing T-cell-depleted allogeneic
bone marrow transplants for de novo AML in first remission have
achieved a DFS of almost 80% with a median follow-up of 4.8 years. A
smaller group of 8 patients with de novo AML in second remission has
achieved a DFS of 50% at a median follow-up of 4 years. Patients
transplanted in first remission were somewhat older than those
represented in most other series. Stratified according to age less than
40 years versus 40 years and older, the product limit estimates for DFS
are nevertheless 81% and 70%, respectively, for patients in first
remission. This broadening of age eligibility for BMT has been
facilitated by the near total elimination of clinical GVHD afforded by
T-cell-depleted allografts as well as the overall improvement in
diagnosis and treatment of posttransplant complications. Accordingly,
26 of the 28 long-term survivors transplanted in either first or second
remission enjoy Karnofsky performance scores of 100%.
All patients reported in this series were in complete remission at the
time of allogeneic transplantation, underscoring the value of current
chemotherapy regimens and supportive care standards used in the primary
treatment of leukemia. The patients transplanted in first CR also
represented a relatively favorable group in that all patients had
primary AML and most achieved CR after a single induction course of
chemotherapy. There was also no exclusion of patients with favorable
karyotypes,10,19 as data supporting their positive outcome
after chemotherapy alone was not widely established when accrual began.
Nevertheless, segregating good risk karyotypes from all others, or
patients requiring single versus more than one induction course to
achieve CR, revealed no significant differences in the outcomes
reported. The median time from diagnosis to transplant in this series
of slightly less than 4 months also avoided the time-censoring bias
that often plagues transplant studies in which patients already
potentially cured by chemotherapy are sometimes overrepresented.
The largest and most current series to date using chemotherapy alone as
postremission treatment is a multicenter Cancer and Leukemia Group B (CALGB) study reported by Mayer et al in
1994.27 This study randomized patients with de novo AML in
first remission to three dose levels of cytarabine for four courses of
consolidation, followed by four uniform monthly cycles of maintenance.
The median age of the overall group was 52 years (range 16 to 86 years), but restricting analyses to those  60 years old showed a
statistically significant advantage in DFS of 44% at 4 years for
patients assigned to receive high-dose cytarabine (3 g/m2/dose × 6 doses). These results extended those
previously reported from smaller series using high-dose
cytarabine28-31 and were comparable to then published
results of allogeneic bone marrow transplants for similar
patients.3,5,8,9,12
Although comparative studies between chemotherapy and unmodified BMT
have not previously shown a survival advantage to BMT, this has not
been because of relapse.3,6,12,32 Rather, any potential
benefits of allogeneic BMT have typically been offset by
regimen-related mortality, complications of GVHD after unmodified allografts,33,34 or graft rejection after T-cell-depleted
transplants.8,16,17
Relapse has never been a significant cause of treatment failure in AML
patients transplanted with T-cell-depleted allografts at this
institution, even when administered after total body irradiation and
cyclophosphamide only.8 This cytoreductive regimen is
commonly used to prepare patients for unmodified allografts where
relapse rates have been higher.3,35,36 This therefore
suggests that the antileukemic effect of a bone marrow allograft,
applied to the treatment of AML in remission, is retained irrespective
of the presence or absence of donor T lymphocytes. These results also
reflect the low tumor burden with which patients with successfully remitted AML begin cytoreduction for BMT.
Hence, the preparative regimen, which now includes thiotepa in addition
to HFTBI and cyclophosphamide, may alone be sufficient to eradicate
residual leukemic cells. Alternatively or in addition, the enhanced
leukemic resistance conferred by a bone marrow allograft is based on
effectors other than the alloreactive T cells in the donor marrow that
cause GVHD. Along these lines, the exceptional patient in this series
with sustained mixed chimerism in blood and/or marrow has not
relapsed. In addition, the two relapses reported in this series could
not have been predicted by antecedent mixed chimerism. Experience at
this and other institutions using donor lymphocytes as salvage therapy
for AML patients relapsing after any type of allogeneic marrow graft
has also shown little success37 (and
unpublished observation). The immunobiology is not well defined, but it
contrasts with that in patients with chronic myelogenous leukemia who
have a much higher tumor burden at the start of cytoreduction, who have
a lower relapse rate after unmodified compared with T-cell-depleted
allografts, and who respond dramatically to infusions of donor
lymphocytes for posttransplant relapse.38-40
In contrast to the previous series of similar patients reported from
this institution in which immune-mediated graft rejection was the
leading cause of treatment failure, affecting 16% of
patients,8 there was not a single case of graft rejection
in this entire group of either first or second remission AML patients.
The current results cannot discriminate whether the additional
chemotherapy or immune suppression is the more critical modification of
the transplant regimen. However, among the patients at risk for
rejection,16-18 the few who have received identical
myeloablative cytoreduction but who have not received antithymocyte
globulin because of anaphylactic reactions have also not suffered
immune-mediated graft rejections.
The data that we have reported from this single institution, phase II
series represents a substantial improvement in durable DFS for AML,
especially in first remission. Improved results after allogeneic BMT
have been reported with recent enhancements in diagnosis and treatment
of transplant complications and when younger patients have been more
numerous in the study population.4,32,35 Bunjes et
al41 recently reported a group of 30 patients (median age
40 years), all but one of whom had AML in first remission, who
underwent HLA identical allogeneic BMT with in vivo and in vitro T-cell
depletion using monoclonal antibodies (MoAbs) Campath 1G/1M. This group also achieved a DFS of approximately 80% but with
shorter follow-up (median 30 months), a higher relapse rate of 10%,
and incidences of 4% acute GVHD grade II and 0% chronic GVHD.
Soiffer et al have also reported encouraging results after
transplantation of bone marrow allografts partially depleted of T cells
with anti-CD6 MoAb and administered after cytoreduction primarily with
a cyclophosphamide/TBI regimen.42 These investigators evaluated 41 patients transplanted in first remission of either acute
lymphocytic (n = 13) or myelogenous leukemia (n = 28). Six of
the 28 patients with AML had antecedent myelodysplastic syndrome (MDS),
and one had received prior chemotherapy for another malignancy. Thirty-four of the 41 patients received matched-related allografts, whereas 7 of the allografts were from related donors mismatched for one
or two HLA loci. The event-free survival for patients with AML was 63%
at 4 years. However, the relapse rate among patients transplanted for
AML in first CR was 31%, with a 15% incidence of grade II to IV acute
GVHD in all recipients of matched-related allografts and a 14%
incidence of chronic GVHD in the group overall.
The low relapse rate, the eradication of immune-mediated graft
rejection, and the near complete elimination of clinically apparent
GVHD largely account for the positive outcomes in this series. This
study therefore supports the continued application and evaluation of
T-cell-depleted allografts to patients with AML in remission,
especially older patients in whom AML is more common. This study also
provides a rationale for comparison with other postremission therapies
considered standard in the management of this disease, and it forms the
basis of a recently opened prospective randomized trial at this
institution to compare T-cell-depleted with unmodified marrow
allografts in the postremission management of acute leukemias.
| |
FOOTNOTES |
Submitted May 22, 1997;
accepted September 24, 1997.
Supported by P01 CA23766 from the National Cancer Institute, National
Institutes of Health; and by the Vincent Astor Chair in Clinical
Research (R.J.O.).
Address reprint requests to James W. Young, MD, Memorial
Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. section 1734 solely
to indicate this fact.
| |
ACKNOWLEDGMENT |
We gratefully acknowledge the expert care provided to these patients by
the fellows and housestaff of Memorial Sloan-Kettering Cancer Center,
as well as the nursing staffs on Memorial 5, 6, and 19, led by Ann
Cleary, RN, Marianne Wallace, RN, Ruth Ford, RN, and Karen Smith, RN.
We also appreciate the unflagging dedication of Catherine Jagiello in
assisting with the T-cell depletions of the marrow grafts. The
commitment and service of our Patient Coordinator, Patricia Walka,
merit special recognition.
| |
REFERENCES |
1.
Mayer RJ:
Current chemotherapeutic treatment approaches to the management of previously untreated adults with de novo acute myelogenous leukemia.
Semin Oncol
14:384,
1987[Medline]
[Order article via Infotrieve]
2.
Berman E,
Heller G,
Santorsa J,
McKenzie S,
Gee T,
Kempin S,
Gulati S,
Andreeff M,
Kolitz J,
Gabrilove J,
Reich L,
Mayer K,
Keefe D,
Trainor K,
Schluger A,
Penenberg D,
Raymond V,
O'Reilly R,
Jhanwar S,
Young C,
Clarkson B:
Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia.
Blood
77:1666,
1991[Abstract/Free Full Text]
3. Appelbaum FR, Fisher LD, Thomas ED, Seattle Marrow Transplant
Team: Chemotherapy v. marrow transplantation for adults with acute
nonlymphocytic leukemia: A five year follow-up. Blood 72:179, 1988
4.
McGlave PB,
Haake RJ,
Bostrom BC,
Brunning R,
Hurd DD,
Kim TH,
Nesbit ME,
Vercellotti GM,
Weisdorf D,
Woods WG,
Ramsay NKC,
Kersey JH:
Allogeneic bone marrow transplantation for acute nonlymphocytic leukemia in first remission.
Blood
72:1512,
1988[Abstract/Free Full Text]
5.
Geller RB,
Saral R,
Piantadosi S,
Zahurak M,
Vogelsang GB,
Wingard JR,
Ambinder RF,
Beschorner WB,
Braine HG,
Burns WH,
Hess AD,
Jones RJ,
May WS,
Rowley SD,
Wagner JE,
Yeager AM,
Santos GW:
Allogeneic bone marrow transplantation after high-dose busulfan and cyclophosphamide in patients with acute nonlymphocytic leukemia.
Blood
73:2209,
1989[Abstract/Free Full Text]
6.
Champlin RE,
Ho WG,
Gale RP,
Winston D,
Selch M,
Mitsuyasu R,
Lenarsky C,
Elashoff R,
Zighelboim J,
Feig SA:
Treatment of acute myelogenous leukemia: A prospective controlled trial of bone marrow transplantation versus consolidation chemotherapy.
Ann Intern Med
102:285,
1985
7.
Copelan EA,
Biggs JC,
Thompson JM,
Crilley P,
Szer J,
Klein JP,
Kapoor N,
Avalos BR,
Cunningham I,
Atkinson K,
Downs K,
Harmon GS,
Daly MB,
Brodsky I,
Bulova SI,
Tutschka PJ:
Treatment for acute myelocytic leukemia with allogeneic bone marrow transplantation following preparation with BuCy2.
Blood
78:838,
1991[Abstract/Free Full Text]
8.
Young JW,
Papadopoulos EB,
Cunningham I,
Castro-Malaspina H,
Flomenberg N,
Carabasi M,
Gulati SC,
Brochstein JA,
Heller G,
Black P,
Collins NH,
Shank B,
Kernan NA,
O'Reilly RJ:
T cell-depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission.
Blood
79:3380,
1992[Abstract/Free Full Text]
9.
Snyder DS,
Chao NJ,
Amylon MD,
Taguchi J,
Long GD,
Negrin RS,
Nademanee AP,
O'Donnell MR,
Schmidt GM,
Stein AS,
Parker PM,
Smith EP,
Stepan DE,
Molina A,
Lipsett JA,
Hoppe RT,
Niland JC,
Dagis AC,
Wong RM,
Forman SJ,
Blume KG:
Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission.
Blood
82:2920,
1993[Abstract/Free Full Text]
10.
Keating MJ,
Smith TL,
Kantarjian H,
Cork A,
Walters R,
Trujillo JM,
McCredie KB,
Gehan EA,
Freireich EJ:
Cytogenetic pattern in acute myelogenous leukemia: A major reproducible determinant of outcome.
Leukemia
2:403,
1988[Medline]
[Order article via Infotrieve]
11.
Mitus AJ,
Miller KB,
Schenkein DP,
Ryan HF,
Parsons SK,
Wheeler C,
Antin JH:
Improved survival for patients with acute myelogenous leukemia.
J Clin Oncol
13:560,
1995[Abstract/Free Full Text]
12.
Schiller GJ,
Nimer SD,
Territo MC,
Ho WG,
Champlin RE,
Gajewski JL:
Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.
J Clin Oncol
10:41,
1992[Abstract]
13.
Terenzi A,
Lubin I,
Lapidot T,
Salomon O,
Faktorowich Y,
Rabi I,
Martelli MF,
Reisner Y:
Enhancement of T cell-depleted bone marrow allografts in mice by thiotepa.
Transplantation
50:717,
1990[Medline]
[Order article via Infotrieve]
14.
Aversa F,
Pelicci PG,
Terenzi A,
Carotti A,
Felicini R,
Mencarelli A,
Donti E,
Latini P,
Aristei C,
Martelli MF:
Results of T-depleted BMT in chronic myelogenous leukaemia after a conditioning regimen that included thiotepa.
Bone Marrow Transpl
7:24,
1991
15.
Mackinnon S,
Barnett L,
Bourhis JH,
Black P,
Heller G,
O'Reilly RJ:
Myeloid and lymphoid chimerism after T-cell-depleted bone marrow transplantation: Evaluation of conditioning regimens using the polymerase chain reaction to amplify human minisatellite regions of genomic DNA.
Blood
80:3235,
1992[Abstract/Free Full Text]
16.
Kernan NA,
Bordignon C,
Heller G,
Cunningham I,
Castro-Malaspina H,
Shank B,
Flomenberg N,
Burns J,
Yang SY,
Black P,
Collins NH,
O'Reilly RJ:
Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants.
Blood
74:2227,
1989[Abstract/Free Full Text]
17.
Bordignon C,
Keever CA,
Small TN,
Flomenberg N,
Dupont B,
O'Reilly RJ,
Kernan NA:
Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: II. In vitro analyses of host effector mechanisms.
Blood
74:2237,
1989[Abstract/Free Full Text]
18. (abstr, suppl 1)
Kernan NA,
Young J,
Papadopoulos E,
Black P,
Small TN,
Mackinnon S,
Castro-Malaspina H,
Childs B,
Gillio A,
Boulad F,
Heller G,
O'Reilly RJ:
Antithymocyte globulin (ATGAM) and methylprednisolone (MP) promote engraftment of T cell depleted (SBA-E-) BMTs from HLA-identical siblings.
Blood
86:621a,
1995
19.
Mrozek K,
Heinonen K,
de la Chapelle A,
Bloomfield CD:
Clinical significance of cytogenetics in acute myeloid leukemia.
Semin Oncol
24:17,
1997[Medline]
[Order article via Infotrieve]
20.
Shank B,
Chu FCH,
Dinsmore R,
Kapoor N,
Kirkpatrick D,
Teitelbaum H,
Reid A,
Bonfiglio P,
Simpson L,
O'Reilly RJ:
Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants.
Int J Radiat Oncol Biol Phys
9:1607,
1983[Medline]
[Order article via Infotrieve]
21. Collins NH, Bleau SA, Kernan NA, O'Reilly RJ: T cell depletion
of bone marrow by treatment with soybean agglutinin and sheep red blood
cell rosetting, in Areman HJ, Deeg HJ, Sacher RA (eds): Bone Marrow and
Stem Cell Processing: A Manual of Current Techniques. Philadelphia, PA,
FA Davis, 1992, p 171
22.
Kernan NA,
Flomenberg N,
Collins NH,
O'Reilly RJ,
Dupont B:
Quantitation of T lymphocytes in human bone marrow by a limiting dilution assay.
Transplantation
40:317,
1985[Medline]
[Order article via Infotrieve]
23.
Glucksberg H,
Storb R,
Fefer A,
Buckner CD,
Neiman PE,
Clift RA,
Lerner KG,
Thomas ED:
Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors.
Transplantation
18:295,
1974[Medline]
[Order article via Infotrieve]
24.
Shulman HM,
Sullivan KM,
Weiden PL,
McDonald GB,
Striker GE,
Sale GE,
Hackman R,
Tsoi M-S,
Storb R,
Thomas ED:
Chronic graft-versus-host syndrome in man: A long-term clinicopathologic study of 20 Seattle patients.
Am J Med
69:204,
1980[Medline]
[Order article via Infotrieve]
25. Kalbfleisch JD, Prentice RL: The statistical analysis of failure
time data. New York, NY, Wiley, 1980
26.
Papadopoulos EB,
Ladanyi ME,
Mackinnon S,
Boulad F,
Carabasi MH,
Castro-Malaspina HC,
Childs BH,
Gillio AP,
Small TN,
Young JW,
Kernan NA,
O'Reilly RJ:
Infusion of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation.
N Engl J Med
330:1185,
1994[Abstract/Free Full Text]
27.
Mayer RJ,
Davis RB,
Schiffer CA,
Berg DT,
Powell BL,
Schulman P,
Omura GA,
Moore JO,
McIntyre OR,
Frei E III,
for the Cancer and Leukemia Group B:
Intensive post-remission chemotherapy in adults with acute myeloid leukemia.
N Engl J Med
331:896,
1994[Abstract/Free Full Text]
28.
Schiller G,
Gajewski J,
Territo M,
Nimer S,
Lee M,
Belin T,
Champlin R:
Long-term outcome of high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia.
Blood
80:2977,
1992[Abstract/Free Full Text]
29.
Wolff SN,
Herzig RH,
Fay JW,
Phillips GL,
Lazarus HM,
Flexner JM,
Stein RS,
Greer JP,
Cooper B,
Herzig GP:
High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: Long-term follow-up and results.
J Clin Oncol
7:1260,
1996[Abstract]
30.
Phillips GL,
Reece DE,
Shepherd JD,
Barnett MJ,
Brown RA,
Frei-Lahr DA,
Klingemann H-G,
Bolwell BJ,
Spinelli JJ,
Herzig RH,
Herzig GP:
High-dose cytarabine and daunorubicin induction and postremission chemotherapy for the treatment of acute myelogenous leukemia in adults.
Blood
77:1429,
1991[Abstract/Free Full Text]
31.
Cassileth PA,
Lynch E,
Hines JD,
Oken MM,
Mazza JJ,
Bennett JM,
McGlave PB,
Edelstein M,
Harrington DP,
O'Connell MJ:
Varying intensity of postremission therapy in acute myeloid leukemia.
Blood
79:1924,
1996[Abstract/Free Full Text]
32. Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B,
Resegotti L, Leoni F, Damasio E, Visani G, Papa G, Caronia F, Hayat M,
Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Vegna ML,
Petti MC, Solbu G, Suciu S, for the European Organization for Research
and Treatment of Cancer (EORTC), and the Gruppo Italiano Malattie
Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups:
Autologous or allogeneic bone marrow transplantation compared with
intensive chemotherapy in acute myelogenous leukemia. N Engl J Med
332:217, 1995
33.
Nash RA,
Pepe MS,
Storb R,
Longton G,
Pettinger M,
Anasetti C,
Appelbaum FR,
Bowden RA,
Deeg HJ,
Doney K,
Martin PJ,
Sullivan KM,
Sanders J,
Witherspoon RP:
Acute graft-versus-host disease: Analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate.
Blood
80:1838,
1992[Abstract/Free Full Text]
34.
Sullivan KM,
Agura E,
Anasetti C,
Appelbaum F,
Badger C,
Bearman S,
Erickson K,
Flowers M,
Hansen J,
Loughran T,
Martin P,
Matthews D,
Petersdorf E,
Radich J,
Riddell S,
Rovira D,
Sanders J,
Schuening F,
Siadak M,
Storb R,
Witherspoon RP:
Chronic graft-versus-host disease and other late complications of bone marrow transplantation.
Semin Hematol
28:250,
1991[Medline]
[Order article via Infotrieve]
35.
Blaise D,
Maraninchi D,
Archimbaud E,
Reiffers J,
Devergie A,
Jouet JP,
Milpied N,
Attal M,
Michallet M,
Ifrah N,
Kuentz M,
Dauriac C,
Bordigoni P,
Gratecos N,
Guilhot F,
Guyotat D,
Gouvernet J,
Gluckman E,
for the Group d'Etude de la Greffe de Moelle Osseuse:
Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: A randomized trial of a busulfan-cytoxan versus cytoxan-total body irradiation as [sic] preparative regimen: A report from the Groupe d'Etudes de la Greffe de Moelle Osseuse.
Blood
79:2578,
1992[Abstract/Free Full Text]
36.
Clift RA,
Buckner CD,
Appelbaum FR,
Bearman SI,
Petersen FB,
Fisher LD,
Anasetti C,
Beatty P,
Bensinger WI,
Doney K,
Hill RS,
McDonald GB,
Martin P,
Sanders J,
Singer J,
Stewart P,
Sullivan KM,
Witherspoon R,
Storb R,
Hansen JA,
Thomas ED:
Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: A randomized trial of two irradiation regimens.
Blood
76:1867,
1990[Abstract/Free Full Text]
37.
Porter DL,
Roth MS,
Lee SJ,
McGarigle C,
Ferrara JLM,
Antin JH:
Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation.
Bone Marrow Transplant
18:975,
1996[Medline]
[Order article via Infotrieve]
38.
Kolb H-J,
Schattenberg A,
Goldman JM,
Hertenstein B,
Jacobsen N,
Arcese W,
Ljungman P,
Ferrant A,
Verdonck L,
Niederwieser D,
van Rhee F,
Mittermueller J,
de Witte T,
Holler E,
Ansari H,
for the European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia:
Graft-vs-leukemia effect of donor lymphocyte transfusions in marrow grafted patients.
Blood
86:2041,
1995[Abstract/Free Full Text]
39.
Porter DL,
Roth MS,
McGarigle C,
Ferrara JLM,
Antin JH:
Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia.
N Engl J Med
330:100,
1994[Abstract/Free Full Text]
40.
Mackinnon S,
Papadopoulos EB,
Carabasi MH,
Reich L,
Collins NH,
Boulad F,
Castro-Malaspina H,
Childs BH,
Gillio AP,
Kernan NA,
Small TN,
Young JW,
O'Reilly RJ:
Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: Separation of graft-versus-leukemia responses from graft-versus-host disease.
Blood
86:1261,
1995[Abstract/Free Full Text]
41.
Bunjes D,
Hertenstein B,
Wiesneth M,
Stefanic M,
Novotny J,
Duncker C,
Heit W,
Arnold R,
Heimpel H:
In vivo/ex vivo T cell depletion reduces the morbidity of allogeneic bone marrow transplantation in patients with acute leukaemias in first remission without increasing the risk of treatment failure: Comparison with cyclosporin/methotrexate.
Bone Marrow Transplant
15:563,
1995[Medline]
[Order article via Infotrieve]
42.
Soiffer RJ,
Fairclough D,
Robertson M,
Alyea E,
Anderson K,
Freedman A,
Bartlett-Pandite L,
Fisher D,
Schlossman RL,
Stone R,
Murray C,
Freeman A,
Marcus K,
Mauch P,
Nadler L,
Ritz J:
CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission.
Blood
89:3039,
1997[Abstract/Free Full Text]
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Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission
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Improved Outcome With T-Cell–Depleted Bone Marrow Transplantation for Acute Leukemia
J. Clin. Oncol.,
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17(5):
1545 - 1545.
[Abstract]
[Full Text]
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|
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Abstract
Introduction
Abstract