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B V A C Ablative Chemotherapy Followed by Autologous Bone Marrow
Transplantation for Patients With Advanced Lymphoma
By Roger D. Gingrich, Gordon D. Ginder, Linda J. Burns, B-Chen W e n , and M a r y A n n e Fyfe
Forty-one consecutive patients with lymphoma resistant to
conventional combination chemotherapy have been entered into a study in which chemo-ablative therapy and
autologous marrow rescue were used with curative intent.
The actuarial proportion of 20 patients with Hodgkin’s
lymphoma remaining alive and free of recurrent disease is
49%. while that for 21 patients with non-Hodgkin’s lymphoma is 41%. Our clinical approach to these patients
involved a strategy whereby lymphomatous nodes greater
than 2 cm in diameter that persisted despite salvage
chemotherapy were given boost radiation therapy immediately before chemo-ablation. However, patients with this
variable had a significantly lower survival due to septic
complications rather than recurrent disease. W e conclude
that the treatment strategy used in this study with some
modification may improve further on the already high
probability of long-term disease-free survival experienced
by this group of patients.
0 1990 by The American Society of Hematology.
0
that our strategic end point could not be attained in many of
these patients, nearly one half of them are predicted to
remain alive and free of tumor for greater than 4 years.
VER T H E PAST 15 years clinical studies in the area of
bone marrow transplantation (BMT) have clearly
documented that selected patients with a variety of malignant diseases refractory to conventional therapy can be
rendered disease-free with a marked escalation of the dosage
and intensity of effective therapeutic modalities. These
patients are given an infusion of stem cells after the ablative
therapy to shorten the expected period of severe hypoplasia.
As long as there is a source of healthy stem cells to replace
the irreversibly damaged bone marrow, treatment strategies
involving this magnitude of dose escalation can be pursued
and have, in effect, created a new class of therapeutic agents.
A second important observation made from some of the
initial studies of BMT is that while ablative doses of therapy
will render some patients free of disease, those patients who
are most likely to remain free of disease for the long-term are
those with minimal disease at the time of their tran~p1ant.l.~
Using these two observations as central premises, we have
developed a treatment program for patients with malignant
lymphoma that is resistant to standard forms of therapy.
Four drugs were chosen for disease ablation based on their
non-shared mechanisms for cell killing and their lack of
overlapping non-marrow, organ system toxicities. At the
time patients were identified with refractory disease defined
as persistent or recurrent after treatment with front-line
conventional chemotherapy, they were studied in a rigorous
fashion to identify all sites of measurable disease. Preablative treatment strategies were tailored for each patient in
an all-out attempt to reduce the patient’s tumor burden.
In this article, we report our experience with 41 consecutive patients referred for autologous bone marrow transplantation (ABMT) for advanced, previously treated Hodgkin’s
(HL) or non-Hodgkin’s lymphoma (NHL). Despite the fact
From the Departments of Internal Medicine and Radiology,
University of Iowa College of Medicine, Iowa City, IA.
Submitted June 5. 1989; accepted February 20, 1990.
Address reprint requests to Roger D. Gingrich, MD. PhD.
Department of Internal Medicine, Univeristy of Iowa Hospitals and
Clinics, Iowa City. IA 52242.
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.
o 1990 by The American Society of Hematology.
0006-497l/90/7512-0026$3.00/0
2276
PATIENTS AND METHODS
Forty-one consecutive patients were accepted for ABMT based on
the following criteria: (1) age of 60 years or less, (2) biopsy-proven
lymphoma persistent or recurrent after a standard multiagent
chemotherapeutic regimen, and (3) bilateral bone marrow biopsies
immediately before the marrow harvest showing a cellularity greater
than 25% and no tumor on a minimum of five step sections through
each biopsy core. A consent form was signed after extensive
consultation with a member of a transplant team and review of an
information summary approved by the Institutional Review Board in
The University of Iowa College of Medicine. For patients with HL,
standard therapy meant the combination of nitrogen mustard,
vincristine, procarbazine, and prednisone (MOPP) or one of the
MOPP-like regimens with disease either persisting or recurring
within 1 year of stopping therapy; or MOPP plus an anthracyclinecontaining regimen if disease recurred greater than 1 year from the
termination of initial therapy. For patients with NHL, standard
therapy meant the combination of cyclophosphamide, doxorubicin,
vincristine, and prednisone (CHOP) or a more aggressive anthracycline-containing regimen.
In addition to the thorough physical examination and the bilateral
bone marrow biopsies, patients also routinely had thoracic and
abdominal-pelvic computed tomographic scans. Lymph nodes greater
than 2 cm in diameter were encompassed in one or two ports, and
involved field radiation therapy was given immediately before the
ablative therapy. To avoid the toxicity from combined chemotherapy
and radiotherapy, a dose of 3,000 cGy in 3 weeks was used for disease
above the diaphragm or 2,500 cGy in 2.5 weeks for disease below the
diaphragm. The patient was admitted for the preparative therapy 7
to 10 days later. Generalized adenopathy was approached using
systemic therapy that was devised for each individual patient with
regard to the drugs the patient had received previously and how they
were felt to have responded. Nitrosoureas were avoided, particularly
if they had been part of the initial regimen. Patients were assessed
carefully for response. Those obtaining a complete response were
taken directly to transplant. Partial responders received involved
field radiotherapy as previously noted.
The ablative regimen is shown in Fig 1 and consisted of BCNU,
600 mg/m2 intravenously (IV) over 2 hours at 2000 hours on day
-8.At 1400hoursondays -7, - 6 , -5,and -4,VP-l6wasinfused
at a dose of 400 mg f m2 over 4 hours. At 2000 hours on day - 7 and
every 12 hours for eight total doses, Ara-C at 3 g/m2 was infused
IV over 90 minutes, At 2000 hours of day -2, cyclophosphamide at
90 mg fkg was infused at a rate of 3,000 mg f h. Anti-emetics in the
form of prochlorperazine and lorezapam were used pretherapy and
Blood, Vol 75, No 12 (June 15), 1990: pp 2276-2281
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ABMT FOR ADVANCED LYMPHOMA
2277
-
days
-
Fig 1. BVAC regimen. Patients were admitted on day - 10 for placement of the indwelling intravenous catheter and baseline studies.
BVAC chemo-ablative therapy was given as indicated with infusion times being 2,4,1.5, and 1 to 2 hours for the BCNU, VP-16, Ara-C, and
cyclophosphamide, respectively. B. BCNU 600 mg/mz; V. VP-16 400 mg/m2; A, Ara-C 3 g/m2; C. cyclophosphamide90 mg/kg.
then as needed. Dexamethasone was routinely given before the
BCNU, each dose of Ara-C and cyclophosphamide such that the
patient received a total dose of approximately 100 mg. Before the
cyclophosphamide, patients were given normal saline at 250 cc/h to
establish a high volume diuresis. The urinary bladder was irrigated
using a three-way catheter immediately before and for 20 hours after
the administration of the cyclophosphamide.
All patients were housed in single rooms on the adult bone marrow
transplant unit at The University of Iowa Hospitals and Clinics.
Each room is ventilated with HEPA-filtered air at four room
exchanges per hour. During the time of neutropenia, patients were
maintained in simple reverse isolation. Individuals entering the room
donned a clean hospital gown and observed thorough hand-washing
practices.
On admission to the transplant unit an indwelling double lumen
intravenous catheter was placed surgically. Surveillance cultures for
bacteria and fungi were done weekly from the skin, nose, throat and
anus. In addition, weekly samples of sera were tested by latex based
agglutination for Candida antigen. Trimethoprim-sulfamethoxazole
in the form of a double strength tablet was given orally twice daily
from day -8 through day - 1 and resumed from day 28 (or
neutrophil count greater than 500) through day 100. Acyclovir was
given three times daily IV from day + 1 at 500 mg/m2 until the time
of engraftment and then switched to 400 mg orally three times daily
until day 100.
Blood products were transfused for a hemoglobin level less than 10
gm/dL or a platelet count less than 20,000. Patients whose serologic
tests for cytomegalovirus (CMV) were negative were given CMV
negative blood products throughout the period of cytopenia. All
blood products were irradiated with 3,000 cGy of gamma radiation
(Gammacell 1000) before transfusion.
Bone marrow was harvested from the posterior iliac crests using
standard techniques. Every patient in this study was harvested after
refractoriness of disease to conventional therapy was identified, with
the majority done after at least one cycle of salvage chemotherapy.
At the time of marrow harvest, a goal of at least 1 x 10' nucleated
cells per kilogram of the patient's body weight was sought. The
marrow buffy coat was separated by centrifugation on a Hemonetics
model 30 (Braintree, MA) with no additional separative or purging
maneuvers. The buffy coat cells were mixed with RPMI 1640
(GIBCO, Grand Island, NY) including a final concentration of
dimethyl sulfoxide (DMSO) at 10%(Cryoserv; Research Industries
Corp, Salt Lake City, UT) and DNAse (Sigma, St Louis, MO) at
1.5 mg/L. The cell suspension was immediately divided into two
equal volumes of 100 mL each, placed in polyolefin bags (Stericon,
Broadview, IL), frozen using a programmable freezer (Cryo-Med,
Mt Clemens, MI); and stored in liquid nitrogen until use. A mean of
1.9 x 10' nucleated cells/kg (range, 0.5 to 4.1 x 108/kg) were stored
for each patient. On the day of transplant, the marrow was retrieved
from the freezer one bag at a time. The marrow was thawed by
placing the bag in a 4OoC waterbath after which it was infused over 5
minutes.
RESULTS
Patients and disease characteristics. Forty-one consecutive patients referred for ABMT have been entered onto this
study. None who met the eligibility requirements were
subsequently excluded for any reason, including progressive
lymphoma. Various characteristics of this group are shown in
Table 1. Twenty patients had HL. Twenty-one patients had
NHL, with fifteen having diffuse large cell lymphoma
(DLCL), three diffuse mixed (DML), and one each with
lymphoblastic, nodular mixed, and nodular poorly differentiated lymphocytic lymphoma. Twenty-six patients (1 3 with
H L and 13 with NHL) had primary refractory disease,
defined as persistent or progressive disease despite first line,
standard combination chemotherapy. The remaining paTable l. Patient Characteristics
Characteristic
HL (n = 20)
NHL In = 21)
Sex (MIF)
Median age (range) yrs
Disease histology
1119
3 3 ( 16-54)
19 NS
1Var
1417
44.5 ( 17-59)
15 DLCL
3 DML
1 NPDL
1 NML
1 LL
13
7
17
6
11
9
2
3
13
8
Disease status at ABMT
Primary refractory
Recurrent disease
Salvage chemotherapy response
Complete
Partial
RT'
No RTt
Salvage RT only*
20
6
14
12
2
1
Abbreviations: NS, nodular sclerosing; Var, sarcomatous variant;
DLCL, diffuse large cell lymphoma; DML, diffuse mixed lymphoma;
NPDL, nodular poorly differentiated lymphoma; NML, nodular mixed
lymphoma; LL, lymphoblastic lymphoma.
*Disease status not reassessed between RT and BMT.
tPatient unable to receive more RT due t o having received maximal
therapy with initial treatment program.
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GlNGRlCH ET AL
tients in each group had recurrent disease after experiencing
at least one complete remission. It was our strategy to
aggressively treat each patient to a minimal disease state (no
lymph node greater than 2 cm in diameter) before their
ablative therapy; however, we found the majority of these
patients to have very resistant disease. Of the entire group,
only four patients (three H L and one NHL) had localized
disease that could be given radiation only before ablative
therapy. The remaining patients required salvage chemotherapy in an attempt to acheive a minimal disease state. Six of
the 17 patients with H L so treated obtained a complete
remission (CR; none with primary refractory disease), while
1 1 obtained a partial or mixed response and were eligible for
involved field radiation therapy because of persistent bulky
disease. Two of the latter patients could not receive radiation
for persistent H L because their sites of recurrence had
previously received maximal treatment. Six of 20 patients
with N H L obtained a C R (three with primary refractory
disease) with salvage chemotherapy, while 12 showed a
partial or mixed response and were then given involved field
radiation therapy. Two in this group were unable to receive
radiation due to previous treatment. In both groups of
patients, salvage chemotherapy was usually given for at least
two cycles, but not more than four cycles, at which time
either a CR or a plateau in the regression of disease/
progression was documented.
Outcome of transplantation. Engraftment of neutrophils (greater than 500 cells/pL) occurred in 33 evaluable
patients at a median of 25 days (range, 14 to 49) from the
time of marrow infusion. Eight patients who were inevaluable died at a median of 13 days (range, 2 to 24) from
transplant. Transfusion-independent platelet counts of greater
than 25,00O/pL were attained in 28 patients at a median
time 30 days posttransplant. Thirteen patients who did not
survive until engraftment died at a median of 20 days (range,
2 to 65) after the marrow infusion. One patient with H L had
bone marrow involvement with tumor at recurrence that was
cleared by salvage chemotherapy. She survives free of
disease 10 months after transplant.
Eleven patients with H L and nine patients with N H L
(seven with DLCL, two with DML) are surviving and have
been continuously free of lymphoma since their transplant,
with the median times of follow-up being 18.7 and 22
months, respectively. As shown in Figs 2 and 3, the actuarial
proportion surviving and continuously free of disease at 48
months is 49% for patients with H L and 41% for those with
NHL.
Nine patients with H L have died, two with persistent and
one with recurrent disease. Four died of sepsis, one had
idiopathic interstitial pneumonitis, and one died of progressive, contracting fibrosis of the mediastinum associated with
recurrent spontaneous pneumothoraces. Four of the six
patients dying of causes other than H L had complete
postmortem examinations, and in none was residual H L
found. The patient who developed progressive mediastinal
fibrosis and consequent respiratory failure expired over 15
months from transplant from a process that was steroidresistant. She was a patient with primary refractory disease
1.0 7
0.2
-I
0.0
I
1
I
I
a
I
I
I
I
I
i
Fig 2. The actuarial (event-free) survival, calculated by the
Kaplan-Meier method, is plotted for all patients with HL entered
onto this study. Forty-nine percent are predicted to remain alive
and well for at least 48 months.
who received 3,000 cGy mediastinal disease before the
ablative therapy.
Twelve patients with N H L have died. Two died of progressive lymphoma diagnosed premortem, while I O patients died
of other causes. Sepsis was the primary cause of death in nine
patients; one died of idiopathic interstitial pneumonia. Five
of these individuals had postmorten examinations, and in
none was residual tumor identified.
In all, 20 patients from both groups currently survive
without recurrent lymphoma. Thus, when one considers the
nine patients who were found to be free of lymphoma at
autopsy, a total of 29 or 70% of the entire group can be said to
have been made disease-free.
Examination of the outcome of transplantation as a
function of response to salvage therapy reveals that I O of 12
patients (five of six in both the H L and N H L group) who
attained a CR with salvage therapy remain alive and free of
tumor (Table 2). This compares with 8 of 21 patients (five of
nine patients with H L and 3 of 12 patients with NHL) who
failed to achieve a CR and required radiation therapy to
residual disease before transplantation. Of the 13 patients
dying in the radiation treatment group, 11 died of sepsis and
two of recurrent lymphoma.
Toxicity. Acute nausea and vomiting was variable in
intensity but was seen to some degree in all patients (Table
3). The majority of patients were maintained on intravenous
hydration throughout the period of ablative therapy despite
the fact that they were able to continue some oral intake of
food. Seven patients subsequently developed a secretory
diarrhea of 3 to 5 L/d, which resolved over 7 to 10 days, and
1.0
0.8
i
ci
..l.l. . . .. . .. . . .. .. .. .. ..I. ...I..
t
O2
0.04
0
I
5
:
10
:
15
;
I
I
20
25
30
:
35
:
40
:
43
!
:
I
50
55
MONTHS
Fig 3. The actuarial (event-free) survival without relapse since
ABMT is plotted for all patients with NHL (see Fig 2, legend); 41 %
are predicted to remain alive and well for over 48 months.
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2279
ABMT FOR ADVANCED LYMPHOMA
Table 2. Outcome of Transplantation Versus Response to
Salvage Therapy
HL
n
Surviving
Disease-Free
NHL
Surviving
Disease-Free
n
Median age
(range) yrs
33 (16-54) 31 (19-47) 44.5 (17-59) 43 (17-59)
Salvage chemotherapy response
Complete
6
5
6
5
Partial
9
5’
12
3’
RT
2
0
2
0
NoRT
2
1
1
Salvage RT only 3
*Outcome was compared within each disease group, as well as by
combining the patients from each disease group by Student’s t test. In
each case, the outcome was significantly worse in the group requiring RT
( P < 10 6).
in most cases showed a partial response to anti-diarrheal
agents. Fifteen patients had stool outputs that remained less
than 500 cc/d.
Stomatitis limiting oral intake and requiring parenteral
pain medications occurred in six patients. Twelve patients
had essentially no symptomatic oral mucosal changes.
Nineteen patients experienced septicemia sometime during their transplant. In 11 patients, this was a single event
involving gram-positive bacteria in five, gram-negative bacteria in four, and fungi in two patients. In eight patients more
than one septicemic event occurred, and in seven this
involved Candida species in addition to bacteria.
Liver function test abnormalities occurred in all but one
patient at sometime during their transplant course but in all
patients these were reversible. Twenty-one patients had an
increase in bilirubin, aspartate aminotransferase (AST)
and/or alkaline phosphatase to greater than five times
normal, with nine having more than one of these tests
elevated. Twelve patients had an elevation of bilirubin a t a
median time of 16 days posttransplant. The maximum level
was 9.7. Twelve patients had an increase in alkaline phosphatase at a median time of 24 days posttransplant. Six
experienced an AST rise peaking at a median of 27 days
posttransplant. Ultrasonographic Doppler studies of portal
Table 3. Toxicities of ABMT
~~~
Toxicitv
Septicemia
Gram-positive bacteria
Gram-negative bacteria
Fungi
Mixed’
Gastrointestinal
Stomatitist
Diarrhea >3 L/d$
Hepatic
Bilirubin >5 x normal
AST >5 x normal
Alkaline phosphatase > 5 x normal
*Candida species (7) plus bacteria.
t Requiring parenteral pain medication.
$Not associated with an infectious etiology.
19
5
1
21
12
6
12
vein, hepatic artery, and inferior vena cava were done in the
majority of patients and revealed no alterations to suggest
hepatic veno-occlusive disease. Three patients with the worst
biochemical abnormalities had liver biopsies and all showed
minimal, nondiagnostic changes. Generally, all abnormalities had resolved by day 120 after transplant.
DISCUSSION
Patients with H L or intermediate/high-grade N H L that
have persistent or recurrent disease after standard, multidrug chemotherapy are at high risk of dying of progressive
lymphoma within 1 to 2 years. Recurrent disease within 1
year of termininating therapy for patients with H L results in
a less than 1-in-5 chance of being rendered disease-free even
with non-cross-resistant combination chem~therapy.’-~
Patients who have recurrent N H L generally succumb to their
disease, although selected patients may experience significant disease-free survival with aggressive but conventionally
dosed chem~therapy.~~’
Clinical data have supported the concept that lymphoma is
a tumor in which there is a steep dose-response curve. Thus,
in studies where doses of chemotherapy have been escalated
in the subablative as well as into the ablative range, patients
not previously
as well as those with relapsed
disease,”“* can be shown to have greater responses than
otherwise would be expected.
In designing the strategy for this clinical study, we used a
bias gained from the early experience with BMT in patients
with resistant leukemia and lymphoma.’,*Our intent was to
treat patients with refractory disease with conventional but
aggressive salvage therapies in order to minimize the patient’s tumor burden before ABMT. Theoretically a t least,
patients with minimal disease at ABMT should be at lower
risk for relapse after the transplant. However, we found the
majority of patients referred to our center for consideration
for ABMT had disease that was very resistant to salvage
chemotherapy and required involved field, boost radiation
therapy as adjunctive therapy pre-ABMT.
Of patients entered onto this study, 40% to 50% are
predicted to remain alive and free of recurrent lymphoma for
greater than 48 months. These results compare very favorably with those reported in the literature, although such
comparisons are difficult due to the admixture of patients
with favorable and unfavorable prognostic features. In a
single center study of 100 patients with primary refractory
(42%) or recurrent H L and N H L prepared with cyclophosphamide and total body irradiation, Appelbaum et all’
reported a 22% 5-year disease-free survival rate. In this
study, both autologous and allogeneic transplants were done
on patients with H L and NHL, and no significant differences
in outcome could be seen when patients with these different
variables were compared.
In a retrospective, multiinstitutional analysis of 100
patients with refractory intermediate- or high-grade N H L
given a variety of ablative regimens, Philip et all4 reported
only a 19% disease-free survival rate at 3 years. Thirty-four
percent of these patients had disease that was refractory to
primary therapy.
Cyclophosphamide and total body irradiation was used by
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2280
GlNGRlCH ET AL
the Johns Hopkins groupI5 to ablate 20 patients with nonacceptable. However, the apparent cost of the markedly
Hodgkin's lymphoma. The median age of this group was 16.5
reduced relapse rate has been an increase in septic deaths. Of
years, and only four patients had primary refractory disease.
the 16 non-tumor, sepsis-related deaths in the study, 13
By actuarial analysis, 50% of this group was disease-free at 3
occurred in patients receiving boost radiation therapy (seven
years.
to the abdomen). The median time to death in this group was
A combination of high-dose cyclophosphamide, etoposide,
14 days from marrow infusion (marrow, 2 to 24). Analysis of
and carmustine (CBV) was used to ablate 128 patients with
the impact of the duration of neutropenia on the risk of
relapsed or refractory Hodgkin's lymph~ma.'~,''
These painfection in patients surviving greater than 30 days from
tients, with a median age of 28 years, received autologous
transplant revealed essentially no difference between those
stem cell support. Thirty-one percent are predicted to remain
with a documeted infection (median time, 26 days; range, 14
alive and free of disease for at least 3 years.
to 44) versus those without infection (median time, 23 days;
Takvorian et all8 have taken a much more selective
range, 14 to 49). It is possible that the toxic effect on the
approach than the current study or any of the previously
gastrointestinal mucosa of salvage chemotherapy and the
cited studies for patients eligible for autologous transplantaradiation therapy boost coupled with that of BVAC predistion, attempting to identify a subset that would do well. Thus,
poses these patients to a high rate of significant sepsis.
Several strategies can be used to salvage patients with
patients with an excellent performance status and who were
lymphoma whose disease persists or recurs after standard
in a clinical complete remission (47%) or minimal disease
state (less than 2-cm nodes or less than 5% tumor on bone
combination chemotherapy. Clearly, further conventionally
marrow biopsy) were offered transplantation. At the time of
dosed chemotherapy or radiation therapy does not salvage
their report 65% of the entire cohort of patients were alive
many patients. Myeloablative therapy either applied in first
and clinically free of disease.
remission" or to a highly selected good risk patient
The tumor ablative potential of the regimens noted above,
population" has improved the outcome of autologous maras well as similar regimens used in other s t ~ d i e s " ~as' ~ ~ 'row
~ ~ grafting
~~
for patients with lymphoma. In this study,
indicated by the proportion of patients relapsing after transconsecutively referred patients were entered onto study and
plantation, appears to be less than for BVAC. In each of
are reported in this article. This study suggests that with a
these studies, the relapse rate is 50% or greater. In the
strategy to aggressively induce patients with persistent or
recurrent lymphoma coupled with a potent ablative therapy
current study, all but two patients had clinically evaluable
disease resolve with the ablative therapy. By virtue of
and ABMT, a significant proportion of patients will become
long-term, lymphoma-free survivors. Modifications of the
continued survival and freedom from relapse or by postmormethods outlined in this article, such as allowing more than 1
tem examination, 70% of the patients have been rendered
to 2 weeks between the pretransplant involved field radiation
free of either clinically or pathologically detectable lymtherapy and beginning ablative therapy, using partial gasphoma. One patient with HL and two with NHL have had
trointestinal decontamination and earlier institution of emrecurrent disease at 12, 3, and 7 months, respectively. We
piric broad-spectrum antibiotics, may be rewarded with an
feel that the overall strategy of aggressive pre-ablative
improvement in the proportion of patients able to achieve
induction to reduce tumor burden plus the use of BVAC with
long-term disease-free survival.
its excellent tumor ablative potential has resulted in a lower
relapse rate for our patients compared with similar groups of
patients reported in the literature. Moreover, when this type
ACKNOWLEDGMENT
of aggressive combination therapy-approach is used, we have
The authors thank the nurses, medical housestaff, and fellows in
found that patients could consistently be made eligible for
the Division of Hematology/Oncology at the University of Iowa
proceeding to transplant.
Hospitals and Clinics for the expert clinical care provided to the
The toxicity from this regimen, other than that pertaining
patients in this study. We also wish to acknowledge the diligence of
Mary Dachtler in typing this manuscript.
to sepsis and, very likely, the gastrointestinal tract, is
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ABMT FOR ADVANCED LYMPHOMA
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From www.bloodjournal.org by guest on June 15, 2017. For personal use only.
1990 75: 2276-2281
BVAC ablative chemotherapy followed by autologous bone marrow
transplantation for patients with advanced lymphoma
RD Gingrich, GD Ginder, LJ Burns, BC Wen and MA Fyfe
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