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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2226-2233
CLINICALOBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Splenectomy in myelofibrosis with myeloid metaplasia: a
single-institution experience with 223 patients
Ayalew Tefferi,
Ruben A. Mesa,
David M. Nagorney,
Georgene Schroeder, and
Murray N. Silverstein
From the Division of Hematology and Internal Medicine, the Division
of Gastroenterologic and General Surgery, and the Cancer Center
Statistics Unit, Mayo Clinic and Mayo Foundation, Rochester, MN.
 |
Abstract |
In a 20-year period, 223 patients (median age, 64.8 years) with
myelofibrosis with myeloid metaplasia (MMM) had therapeutic splenectomy at our institution. Primary indications for surgery were
transfusion-dependent anemia (45.3%), symptomatic splenomegaly (39.0%), portal hypertension (10.8%), and severe thrombocytopenia (4.9%). Operative mortality and morbidity rates were 9% and 31%, respectively. The 203 survivors of surgery had a median postsplenectomy survival time (PSS) of 27 months (range, 0-155). Among preoperative variables, thrombocytopenia (platelet count less than 100 × 109/L) and nonhypercellular bone marrow were identified as
independent risk factors for decreased PSS. Durable remissions in
constitutional symptoms, transfusion-dependent anemia, portal
hypertension, and severe thrombocytopenia were achieved in 67%, 23%,
50%, and 0% of the patients, respectively. Histologic or cytogenetic
features of bone marrow obtained before splenectomy did not predict a
response in cytopenias. After splenectomy, substantial enlargement of
the liver and marked thrombocytosis occurred in 16.1% and 22.0% of the patients, respectively. The thrombocytosis was associated with an
increased risk of perioperative thrombosis and decreased PSS. The rate
of blast transformation (BT) was 16.3%, and the risk of BT was higher
in the presence of increased spleen mass and preoperative
thrombocytopenia. However, the PSS of patients with BT was not
significantly different from that of patients without BT. We conclude
that presplenectomy thrombocytopenia in MMM may be a surrogate for
advanced disease and is associated with an increased risk of BT and
inferior PSS. However, the development of BT after splenectomy may not
affect overall survival and does not undermine the palliative role of
the procedure for the other indications.
(Blood. 2000;95:2226-2233)
© 2000 by The American Society of Hematology.
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Introduction |
The term "myelofibrosis with myeloid metaplasia"
(MMM) includes agnogenic, postthrombocythemic, and postpolycythemic
myeloid metaplasia.1 The disorder is a clonal stem cell
disease in which reactive bone marrow fibrosis develops, mediated by
megakaryocyte-derived fibrogenic cytokines.2-4 Replacement
of normal hematopoietic tissue with collagen fibrosis contributes to
the underlying ineffective hematopoiesis and erythroid
hypoplasia.5,6 Morphologic and kinetic data indicate that
bone marrow fibrosis in MMM is accompanied by extramedullary
hematopoiesis, which causes progressive enlargement of the spleen
and liver.7 The resultant organomegaly causes pain and early satiety and promotes weight loss, portal hypertension, and profound fatigue. Furthermore, splenomegaly leads to exacerbation of cytopenias through sequestration and destruction of
hematopoietic elements.
The reported median survival time of patients with MMM ranges from 3 to
8 years.5,8-11 Treatment is largely palliative and has not
been shown to improve survival.12 Anemia and
thrombocytopenia may improve transiently with drug therapy. Androgen
preparations and corticosteroids are the most effective agents, whereas
the benefit of  -interferon and erythropoietin is
limited.13-18 Early results from the use of allogeneic bone
marrow transplantation are promising.19,20 Nevertheless,
the mainstays of current therapy are transfusions of red blood cells
and administration of hydroxyurea to reduce spleen size.21
Although bone marrow erythroid hypoplasia and ineffective hematopoiesis
are primarily responsible for the cytopenias occurring in
MMM,6 cytopenias in chronic myeloproliferative diseases are
exacerbated by marked splenomegaly, even in the absence of associated
myelofibrosis.22 Removal of the enlarged spleen in patients
with MMM has been shown to decrease plasma volume and peripheral
hemolysis and perhaps to increase erythropoietic activity of the bone
marrow.23 Although hematopoietic stem cells circulate in
the peripheral blood of patients with MMM, they are usually absent in
splenic tissue, which may instead facilitate their
differentiation.24 Additional evidence suggests that, in
this situation, the hematopoietic role of the spleen may be limited to
the expansion of committed progenitors and not necessarily their
terminal differentiation.25-29 Therefore, a direct
reduction of excess splenic tissue in patients with MMM may have a
favorable effect on peripheral cytopenia. This reduction can be
accomplished by either external beam irradiation30 or
splenectomy.31-44
Removal of the spleen as a therapeutic intervention in MMM has been
investigated. Before 1940, the procedure was considered dangerous and
reportedly had an operative mortality rate of 30% to
50%.37,45 Recently, however, improvements in surgical
technique, patient selection, and perioperative care have made
splenectomy in patients with MMM a safer and more accepted practice,
with reported perioperative mortality rates of 7% to
15%.31-34,38 On the other hand, splenectomy has not been
shown to improve overall survival of patients with MMM,46
and the palliative benefit of the procedure should be weighed against
the risk of perioperative and long-term complications.
In this report, we describe a single-institution experience with 223 consecutive cases of therapeutic splenectomy in patients with MMM. We
provide overall operative mortality and morbidity rates, estimates of
postsplenectomy survival and complication rates, and analysis of
benefits and prognostic factors.
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Patients and methods |
Patients
After approval for this study was obtained from our institutional
review board, the study patients were identified through the use of a
comprehensive institutional database of medical diagnoses and
procedures. The medical records of all patients with MMM who had
splenectomy during the period of 1976 through 1996 were reviewed. The
diagnosis of MMM was confirmed on the basis of traditional diagnostic
criteria that included bone marrow fibrosis associated with
splenomegaly and leukoerythroblastosis.47,48 Patients with
bone marrow fibrosis due to other clonal or nonclonal disorders were
excluded. These included patients with myelodysplastic syndrome, acute
myelofibrosis, or chronic myelogenous leukemia.
Pertinent preoperative variables were recorded for all patients (Table
1). In addition, postoperative variables
were recorded 1, 6, and 12 months after splenectomy and at the time of
the latest contact with the patient. Patients were categorized
according to 1 of 4 primary indications for splenectomy: (1)
symptomatic splenomegaly (severe mechanical discomfort or pain, with or
without constitutional symptoms); (2) severe anemia (hemoglobin level less than 90 g/L or a need for transfusion of red blood
cells); (3) symptoms and signs of portal hypertension; and (4) severe thrombocytopenia (platelet count less than 20 × 109/L). Patients were assigned a prognostic score
based on the findings of Dupriez et al.8 A score of 0 was
assigned for a hemoglobin level of more than 100 g/L and a white blood
cell count between 4 × 109/L and
30 × 109/L, a score of 1 was assigned for either a
hemoglobin level of less than 100 g/L or a white blood cell count of
more than 30 × 109/L or less than
4 × 109/L, and a score of 2 was assigned if both
the hemoglobin and white blood cell values were in those aberrant
ranges.
Improvement in constitutional symptom status was defined as a more than
50% improvement in fatigue, a more than 50% recovery of preoperative
weight loss, or disappearance of night sweats and fever. All
complications occurring within the first 45 days after surgery were
classified as perioperative complications. Accelerated hepatomegaly was
defined as an increase in palpable liver size that extended more than 6 cm below the right costal margin (or a 6-cm increase from the baseline
location in patients with palpable hepatomegaly before splenectomy).
Extreme thrombocytosis was defined as a postsplenectomy platelet count
of at least 600 × 109/L (or a platelet count of at
least 1000 × 109/L in patients who had
thrombocytosis before splenectomy). Leukemic transformation was
confirmed by demonstration of more than 30% blasts in the bone marrow.
Statistical analysis
Postsplenectomy survival was defined as the interval from
splenectomy to death or latest contact. In the analysis of
postsplenectomy survival, an event was defined as death from any cause,
unless otherwise indicated. Multiple preoperative clinical variables were studied for their influence on both perioperative complications and overall postsplenectomy survival. Univariate analyses to assess the
independent effects of categorical preoperative variables on
postsplenectomy survival were performed by creating survival curves
with use of the Kaplan-Meier method and comparing these with 2-sided
log-rank statistics. Univariate analysis to assess the independent
effects of continuous preoperative variables on postsplenectomy
survival was done with the Cox proportional hazards method. For
analyses other than postsplenectomy survival, univariate logistic
regression models were used to assess the association between binary
dependent variables and continuous variables.
The Spearman rank correlation coefficient was used for a pair-wise
comparison of the strength of the association between variables. A
series of multivariate Cox proportional hazards regression models were
generated to assess whether various factors had a significant effect on
overall postsplenectomy survival and perioperative survival. Multivariate logistic regression models were generated to assess whether various factors had a significant effect on bleeding, thrombosis, leukemia, hepatomegaly, and thrombocytosis. The
multivariate model-building process involved examining models proposed
by forward-selection and backward-elimination procedures as well as
models identified by the score method that contained 2, 3, and 4 variables. The findings from the score method were compared with those
from the forward-selection and backward-elimination model-building
procedures to identify subsets of factors with possible clinical
relevance. All data were analyzed by using SAS software (SAS, Cary, NC).
| |
Results |
Patient characteristics
A total of 223 patients with MMM had therapeutic splenectomy at our
institution from 1976 through 1996. Table 1 shows their clinical
characteristics at the time of splenectomy. Most patients (71.3%) had
agnogenic myeloid metaplasia; the rest had either postpolycythemic
myeloid metaplasia or postthrombocythemic myeloid metaplasia. The most
common indications for surgery were anemia (45.3%) and symptomatic
splenomegaly (39.0%). Risk stratification according to the
Dupriez-based prognostic scoring system both at the time of initial
diagnosis and at the time of splenectomy is shown in Table
2. Splenectomy was performed a median of
24.7 months (range, 0-385) after the initial diagnosis. The interval was significantly shorter in patients with a prognostic score of 2 at
diagnosis than in those with a score of zero or 1. The median (range)
intervals from diagnosis to splenectomy, according to indication for
surgery, were 21.7 months (0-184) for anemia, 29.5 months (0.1-385) for
symptomatic splenomegaly, 24.3 months (0.1-97) for severe
thrombocytopenia, and 52.9 months (0.5-188) for portal hypertension
(P = .69).
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Table 2.
Prognostic stratification at initial diagnosis and at
time of splenectomy and its influence on time to splenectomy and
survival in 223 patients with MMM
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Perioperative complications
Sixty-eight patients (30.5%) had perioperative complications in the
first 45 days after splenectomy; 14.8% had bleeding, 8.5% had
infection, and 7.2% had thrombosis (Table
3). The complications occurred a median of
3 days postoperatively and were fatal in 19 patients. Causes of
perioperative death (20 patients) included bleeding in 10 patients
(4.5%), infection in 6 (2.7%), thrombosis in 3 (1.3%), and acute
myeloid leukemia in 1. Univariate analysis was done to determine
whether any preoperative clinical variables were predictive of
perioperative bleeding or thrombosis (Table 4). Thrombocytopenia (platelet
count < 100 × 109/L) was the only preoperative
variable that was significantly correlated with postoperative
thrombosis. Severe thrombocytopenia (platelet count < 50 × 109/L) and bone marrow hypocellularity or
normocellularity were significantly associated with a worse
perioperative survival (Table 5). The findings were similar on multivariate analysis.
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Table 4.
Univariate analysis of preoperative variables as
possible prognostic factors for 2 perioperative complications of
splenectomy in 223 patients with MMM
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Table 5.
Univariate analysis of the correlation between
preoperative variables and perioperative and overall postsplenectomy
survival in 223 patients with MMM
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Benefit analysis
Palliative outcome varied according to the primary indication for
surgery (Table 6). All evaluable patients
who underwent splenectomy for symptomatic splenomegaly had relief from
mechanical discomfort. In addition, an improvement in
constitutional-symptom status was observed in 94%, 80%, and
67% of patients at 1, 6, and 12 months, respectively, after
splenectomy. Among patients who had splenectomy for anemia, 37.6% had
a quantitative improvement that consisted of either having no further
need for red blood cell transfusions or achieving a durable increase of
more than 10 g/L in hemoglobin level. Of the 75 patients who were
dependent on red blood cell transfusions at the time of surgery, 30%
became independent of transfusions by 6 months postoperatively, and the benefit was sustained in 23% at latest follow-up. Twenty-four patients
underwent splenectomy because of symptomatic portal hypertension, and
an overall improvement was observed in 67% of these patients at 6 months and in 50% at 12 months after splenectomy. This improvement included a substantial reduction in ascites or bleeding from
gastrointestinal varices. No durable benefit was observed in patients
who had splenectomy for severe thrombocytopenia. Postsplenectomy
improvement in anemia was not influenced by presplenectomy bone marrow
cellularity, degree of collagen fibrosis, or the presence of
cytogenetic abnormalities.
Leukemic conversion
After a median follow-up of 14.4 months (range, 0.23-157) after
splenectomy, blast transformation developed in 33 patients (16.3% of
those who survived splenectomy). Blast transformation occurred a median
of 4.9 years after the initial diagnosis of MMM (range, 0.25-12.6) and
1.9 years after splenectomy (range, 0.13-7.9). The overall
postsplenectomy survival in patients in whom blast transformation
developed was not significantly different from that in those who did
not have leukemic transformation (median survival, 25.6 compared with
23.9 months; P = .79). Univariate analysis of preoperative
clinical characteristics revealed a significant association between
blast transformation on one hand and an increased splenic mass and
severe thrombocytopenia (platelet count less than 50 × 109/L) on the other (Table 7).
However, the presence of either cytogenetic abnormalities or a bone
marrow blast percentage more than or equal to 5% was not predictive of
blast transformation. The findings were similar on multivariate
analysis.
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Table 7.
Univariate analysis of correlation between preoperative
variables and long-term complications in 223 patients with MMM who
underwent splenectomy
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Postsplenectomy enlargement of the liver and thrombocytosis
Postsplenectomy hepatomegaly (palpable liver extending more
than 6 cm below the right costal margin) was observed in 36 patients (16.1%), and in 25 of these patients, the palpable liver
extended 10 cm below the right costal margin. Univariate analysis of
preoperative clinical characteristics revealed no significant
predictors of postsplenectomy hepatomegaly (Table 7). Furthermore, the
development of postsplenectomy hepatomegaly did not result in inferior
survival. Postsplenectomy thrombocytosis (platelet count greater than
600 × 109/L) was observed in 49 patients (22.0%),
13 (5.8%) of whom had a platelet count of more than
1000 × 109/L. Preoperative platelet counts of
more than 50 × 109/L were predictive of
postsplenectomy thrombocytosis (Table 7). Postsplenectomy
thrombocytosis was associated with increased perioperative thrombosis
(P = .05) and decreased overall survival (P = .01). Of the 49 patients with postsplenectomy thrombocytosis, 9 (18%) died
of either thrombosis (6 patients who had stroke, pulmonary embolus, or
portal vein thrombosis) or gastrointestinal bleeding (3 patients).
Survival
The median overall survival time was 5.8 years (range, 0-12.9) after
the initial diagnosis of MMM and 2 years (range, 0-12.9) after
splenectomy (Figure 1 and
2). Prognostic stratification at either
diagnosis or splenectomy did not reveal any significant overall or
postsplenectomy survival differences (Table 2). At latest contact, a
total of 132 patients (59.1%) had died. Of these, 20 (15.2%) died of
perioperative complications. Causes of death not related to surgery
included acute leukemia in 29 patients (22%), bleeding in 16 (12%),
thrombosis in 11 (8%), liver failure in 9 (7%), infection in 6 (5%),
other malignant diseases in 7 (5%), and cardiac events in 6 (5%). One
patient died of cardiac extramedullary hematopoiesis. The immediate
cause of death in the other patients could not be determined
accurately.
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| Fig 1.
Overall survival after initial diagnosis of MMM of 223 consecutively treated patients who had therapeutic splenectomy.
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| Fig 2.
Survival after splenectomy of 223 consecutively treated
patients with MMM who had therapeutic splenectomy.
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The particular subtype of MMM did not have a significant influence on
either overall or postsplenectomy survival. Similarly, the
postsplenectomy survival of patients with different indications for
surgery was similar, although there was a trend toward inferior survival in patients with severe thrombocytopenia (Figure
3). Univariate analysis involving several
preoperative characteristics identified preoperative thrombocytopenia
and bone marrow hypocellularity or normocellularity as the only
variables predictive of decreased postsplenectomy survival (Table 5 and
Figure 4). In a multivariate proportional
hazards regression model, both these variables were found to be
independently significant (P = .0003 and P = .01, respectively). On the other hand, postsplenectomy thrombocytosis (platelet count greater than 600 × 109/L) was
associated with decreased postsplenectomy survival (P = .01).
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| Fig 4.
Survival after splenectomy of patients with MMM,
according to presplenectomy bone marrow cellularity.
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Discussion |
Our series of 223 patients with MMM who underwent splenectomy
represents the largest single-institution experience compiled. In
contrast to previous observations,34 we found that overall and postsplenectomy survival time and surgical outcome were similar among patients with agnogenic myeloid metaplasia, postpolycythemic myeloid metaplasia, and postthrombocythemic myeloid metaplasia. In
general, our results confirm a high incidence of
perioperative mortality (9%) and morbidity (30.5%). Incidence rates
improved substantially in reports that appeared after 1940 compared
with those published earlier.37 Since then,
however, the reported operative mortality rates of 7% to 15% have not
changed much.31-34,38 Bleeding, infection, and thrombosis
are the leading causes of perioperative mortality and morbidity. In the
current study, preoperative thrombocytopenia was significantly
associated with perioperative thrombosis and decreased
survival. In addition, presplenectomy bone marrow
hypocellularity or normocellularity was also independently associated
with a worse perioperative survival. However, both this study and a
previous multicenter study involving 71 patients did not find any other
preoperative clinical characteristics to be helpful in predicting
surgical outcome.32 The paradoxic association of
preoperative thrombocytopenia with postoperative thrombosis suggests
the possibility that affected patients had occult disseminated intravascular coagulopathy. All of our patients, however, were systematically evaluated for the presence of this condition, and previous studies found that disseminated intravascular coagulopathy was
associated with increased postsplenectomy hemorrhage but not thrombosis.13
Despite the relatively high rate of perioperative complications, a
substantial number of patients with MMM had a durable benefit from
splenectomy. Success was most likely in patients with mechanical symptoms from massive splenomegaly and profound constitutional symptoms. In particular, performance status, stamina, and body weight
improved in most of our patients. Consistent with previous observations,13,32,37 less than one-half of our patients
with anemia had a durable remission. Moreover, presplenectomy bone marrow cellularity or degree of collagen fibrosis did not predict a
response in patients with anemia. Other benefits of splenectomy included alleviation of symptoms and signs of portal hypertension due
to increased portal flow; however, portal hypertension caused by
intrahepatic or portal vein obstruction may require portal-systemic shunt surgery.49 Splenic irradiation used as an alternative to splenectomy may provide relief from mechanical
symptoms.30 However, the benefit is transient, and
life-threatening cytopenias may occur in up to 44% of patients.
Furthermore, operative risk may be increased in patients who may
subsequently undergo splenectomy. Therefore, irradiation is reserved
for patients who are poor candidates for surgery.
Substantial postsplenectomy hepatomegaly occurred in 16% of our
patients. Previously reported incidence rates for this disorder range
from 16% to 24%, with the range reflecting differences among studies
in the selection of evaluable patients and the follow-up period.31,32,34 In the current study, the development of
postsplenectomy hepatomegaly was not predicted by preoperative clinical
variables and did not affect survival after splenectomy.
Others32 found a significant correlation between
transfusion-dependent anemia as a indication for surgery and the
subsequent development of postsplenectomy hepatomegaly. Extramedullary
hematopoiesis is the primary cause of postsplenectomy hepatomegaly and
may coexist with additional histologic features of periportal fibrosis,
hemosiderosis, microvascular portal vein thrombosis, and hepatic
nodular regenerative hyperplasia.50,51 Nevertheless,
postsplenectomy hepatomegaly seldom progresses to liver failure and is
not a major cause of death. Liver failure was the direct cause of only
7% of the deaths in our series and of zero to 20% of deaths in other
series.32,50 Treatment with hydroxyurea or
2-chlorodeoxyadenosine may be considered in patients in whom
postsplenectomy hepatomegaly develops.52
In the present study, the incidence of extreme thrombocytosis after
splenectomy was 22%. Incidence rates in other series vary from 18% to
50%, and this wide range may reflect differences in the timing and
aggressiveness of myelosuppressive therapy.31,32,34,35 Postsplenectomy thrombocytosis has been associated with the occurrence of thrombotic and hemorrhagic events.31,32,34,35 Similarly, we found significant associations between postsplenectomy
thrombocytosis on one hand and perioperative thrombosis and worse
postsplenectomy survival on the other. In our study, a preoperative
platelet count of more than 50 × 109/L was
predictive of postsplenectomy thrombocytosis, whereas
others32 found an increased thrombohemorrhagic risk with
preoperative platelet counts of more than
200 × 109/L. Of note, the actual incidence of
postsplenectomy thrombosis may be higher than what is recognized
clinically; thus, its overall impact on postsplenectomy survival
remains undefined.53 Although increased platelet
hyperaggregability may contribute to perioperative thrombosis, the high
incidence of perioperative bleeding may not allow the prophylactic use
of acetylsalicylic acid.54 However, preoperative
institution of prophylactic platelet-lowering therapy may reduce the
incidence and severity of postsplenectomy thrombocytosis and any
thrombosis associated with it.
Overall median survival time in MMM has not changed in recent years and
ranges from approximately 3 to 8 years.5,8-12,55,56 Various
prognostic factors have been used to identify a group of patients with
relatively long (greater than 10 years) or short (less than 2 years)
survival.5,8,11,57,58 Because of the retrospective nature
of studies involving patients with MMM who have undergone splenectomy,
the effect of the procedure on overall survival may not be assessed
accurately. In reports on cohorts that included both patients who had
undergone splenectomy and patients who had not, overall survival after
the time of diagnosis was not stated to be different in the 2 groups.8,59 Similarly, when patients with early-stage
disease who had undergone splenectomy were compared with historical
controls who received medical therapy, overall survival was not
significantly different.46 However, most patients with MMM
who are offered therapeutic splenectomy have advanced-stage disease and
may also have disease characteristics not recognized by current
prognostic criteria. Nevertheless, the observed overall median survival
of 5.8 years in our study compares favorably with the corresponding
values for high-risk disease and suggests the lack of an adverse effect
on survival.
Reported rates of postsplenectomy survival and blast transformation
vary widely because of disparities in sample size, patient selection,
the definition of blast transformation used, and duration of follow-up.
Also, perioperative deaths may or may not be included in the survival
analysis. In our group of 223 patients, the median postsplenectomy
survival time and the incidence of blast transformation among the 203 survivors of surgery were 27 months and 16%, respectively. Our results
compare favorably with those of an analysis of 321 published cases that
reported a median postsplenectomy survival of 13 months and a blast
transformation rate of 11.2%.37 In contrast, a multicenter
Italian study involving 71 patients reported a median postsplenectomy
survival time of 55 months among the 65 patients who survived
surgery.32 The superior survival time in the Italian study
may be related partly to the younger age of the study
population59 (median of 55 years compared with 65 years in
the current study). This may also account for the higher proportion of
deaths from leukemia in the Italian study (43% compared with 22% in
the current study and 11.2% in previous series).37
Similarly, the relatively lenient criteria used to define blast
transformation and the longer follow-up period may account for the
higher incidence of blast transformation (26% compared with 16% in
the present series). Still, concern has been raised about the
leukemogenic potential of splenectomy in MMM.
The Italian study59 compared 87 patients with MMM who had
undergone splenectomy with a cohort of 462 patients who had not had the
procedure and reported crude incidence rates of blast transformation of
26% and 12%, respectively, in the 2 groups. To adjust for clinical
differences between the 2 groups, the authors applied statistical
models of multivariate analysis (Cox proportional hazards model and
recursive partitioning) and found splenectomy to be an independent risk
factor for blast transformation. Despite the complementary role of the
2 multivariate models, however, both are based on consideration of
known risk factors and may not adjust for hidden confounders. The fact
that current prognostic criteria were not validated by the results in
our patient cohort suggests that imminent splenectomy identifies a
biologically different subset of
patients.5,8,57 Furthermore, histopathologic
studies of the spleen have suggested that subclinical blast
transformation may influence the need for splenectomy and therefore
account for the apparent increase in blast
transformation.60 Other studies, however, did not find
increased leukemic conversion rates after splenectomy,8 and
our experience and that of others37 suggest that
postsplenectomy survival may not be affected by the development of
blast transformation. Therefore, an appropriate surgical recommendation should not be waived for fear of increased risk of leukemia and compromised survival.
The prognostic value of bone marrow histologic features and cytogenetic
profile in assessing postsplenectomy outcome was examined in the
current study. It should be noted, however, that because particular
studies were not always performed either in all the patients or at the
time of splenectomy, the statistical findings are not conclusive.
Nevertheless, the presence of bone marrow hypercellularity was
significantly associated with both an overall and a postsplenectomy
survival advantage, and this finding is consistent with previously
described associations between inferior survival and bone marrow
hypocellularity in MMM.11 Both bone marrow hypocellularity
or normocellularity and presplenectomy thrombocytopenia were
independently associated with worse postsplenectomy survival and may be
surrogates for either advanced or aggressive disease. In contrast, we
did not detect significant correlations between the degree of collagen
fibrosis and postsplenectomy outcome. This finding is also consistent
with previous studies that showed a lack of significant association
between bone marrow fibrosis and overall survival in MMM.5
Finally, although abnormal cytogenetic findings have been associated
with poor survival in agnogenic myeloid metaplasia,2 their
detection in bone marrow obtained from patients before splenectomy in
our study did not predict either worse survival or a higher risk of
leukemic transformation.
In summary, the current study demonstrated that a durable benefit can
be achieved in most patients with MMM who have splenectomy for the
treatment of severe constitutional symptoms associated with marked
splenomegaly and portal hypertension. In such patients, the improvement
in quality of life may justify the relatively high risk of operative
death.33 In contrast, severe thrombocytopenia may not be
improved by splenectomy, and thrombocytopenia generally may be a
surrogate for advanced disease with a poor surgical outcome. The
selection of splenectomy to treat transfusion-dependent anemia should
be based on the individual case and may be reserved for patients in
whom drug therapy has failed and whose quality of life is compromised
by the need for frequent transfusions. In addition, the superior
postsplenectomy survival that was observed in patients with
hypercellular bone marrow histologic features may allow consideration
of bone marrow cellularity as an additional selection factor for
splenectomy in patients with anemia. The currently available
information indicates that splenectomy does not appear to either retard
or hasten the progression of MMM. Similarly, whether or
not the procedure increases the rate of blast transformation may not
have major clinical relevance because overall survival may not be
affected and the palliative benefit may outweigh any excess risk.
Prophylactic myelosuppressive therapy may decrease the risk of
perioperative thrombosis associated with postsplenectomy thrombocytosis
and improve overall survival.
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Footnotes |
Submitted July 23, 1999; accepted December 1, 1999.
Murray N. Silverstein died on September 15, 1998.
Reprints: Ayalew Tefferi, Division of Hematology and Internal
Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
The publication costs of this
article were defrayed in part by
page charge payment. Therefore,
and solely to indicate this fact,
this article is hereby marked
"advertisement"
in accordance with 18 U.S.C.
section 1734.
| |
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Top
Abstract
Introduction