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CORRESPONDENCE Splenomegaly is one of the characteristics of agnogenic myeloid
metaplasia and other syndromes associated with myelofibrosis. If spleen
enlargement is massive, patients may be severely symptomatic with
abdominal pain, early satiety, and other manifestations. Splenectomy is
effective in relieving symptoms, but surgical mortality is in the range
of 5%-10%. Furthermore, there is concern about postsplenectomy
thrombocytosis and associated complications, and some reports have
suggested an increased probability of leukemic transformation.1 Tefferi et al recently reviewed results
in 223 patients with agnogenic myeloid metaplasia who underwent
splenectomy at the Mayo Clinic.2 The most frequent
indications were transfusion-dependent anemia and symptomatic spleen
enlargement. Patients with thrombocytopenia had an increased
probability of postsplenectomy blast transformation, although this did
not result in shortened survival. Symptoms related to splenomegaly
resolved permanently in two thirds of the patients. Hemopoietic cell transplantation offers the potential of cure for
patients with agnogenic myeloid metaplasia and other hematopoietic disorders associated with marrow fibrosis.3 Patients with
myelofibrosis who are being considered for transplantation generally
have marked splenomegaly. In addition to problems as discussed above,
splenomegaly in these patients also raises concerns about excessive
sequestration of transplanted stem cells and difficulties with
transfusion support after transplantation,1,4 which in
turn may affect transplant outcome. We reviewed our experience in 26 patients with myelofibrosis and splenomegaly who underwent hemopoietic
cell transplantation and who have been followed for a minimum of 2 years. Eleven patients had undergone splenectomy before receipt of
transplant, and 15 received their transplant with an enlarged spleen in
place. Patient and transplant characteristics are summarized in Table
1.
Disease duration was 4-252 months (median, 37.5 months) for patients
with splenectomy and 1-144 months (median, 14 months) for patients
without splenectomy (P = NS). Among patients without splenectomy, all had splenomegaly with spleen sizes ranging from 4 cm
to 23 cm below the costal margin. In splenectomized patients a specific
description of spleen size was not uniformly available, but in all
cases the spleen was described as markedly or massively enlarged.
Patients in the 2 groups received a median of 3.5 (range 0.6-14.9) and
3.5 (1.8-31) × 108 nucleated cells/kg, respectively
(P = NS). Two patients with splenectomy and one without
splenectomy received peripheral blood stem cells; the remaining
patients received transplants of marrow cells. All were given
methotrexate plus cyclosporine for graft-versus-host disease (GVHD)
prophylaxis. All patients achieved sustained engraftment. The median
time (range) to reach granulocyte counts of 0.5 and 1.0 × 109/L among splenectomized patients was 18 (14-51)
and 22 (15-54) days, respectively. The corresponding time points for
patients without splenectomy were 23 (19-85) and 25 (20-28) days,
respectively. These differences were significant, both for 0.5 and
1.0 × 109 ANC/L (P = .04 and
P = .03, respectively). (Information for
1 × 109 granulocytes was missing in one
splenectomized patient.) Platelet counts of at least
20 × 109/L were reached at 15.5 (8-93) days in 9 of 11 splenectomized patients and at 19 (11-48) days in 10 of 15 nonsplenectomized patients (P = NS); 7 patients died
without reaching platelet counts of at least 20 × 109/L.
The incidence rates of acute GVHD of at least grade II were comparable
(63% with splenectomy and 66% without splenectomy); no patient had
grade IV, and only 1 had grade III acute GVHD. Chronic GVHD developed
in 6 of 10 patients at risk with splenectomy and in 5 of 13 patients
without splenectomy. Disease-free survival at 3 years was 73% for
splenectomized and 64% for nonsplenectomized patients
(P = NS; Figure 1). Two
patients in the splenectomy group experienced a disease relapse after
transplantation. Overall, 3 splenectomized patients and 5 nonsplenectomized patients have died. Among splenectomized patients,
causes of death included organ failure and infection in 2 patients and
disease recurrence in 1 patient. Among patients with the spleen intact,
5 patients died either from organ failure and infection (n = 2), GVHD
and infection (n = 1), infection (n = 1), or lymphoma (n = 1).
Thus patients with splenectomy had faster posttransplantation granulocyte recovery than nonsplenectomized patients. Otherwise, the present results provide no evidence for either a significant advantage or disadvantage of splenectomy on posttransplantation outcome. This analysis has all the shortcomings of a small, retrospective, nonrandomized study. There may well be other important differences between the splenectomized and nonspelenctomized patients. For example, pretransplantation disease duration was somewhat longer (albeit not significantly so) in splenectomized patients, and although not the case in the present study, disease duration has been found to be inversely correlated with posttransplantation outcome for other indications. In addition, splenectomized patients tended to be older and more often received a transplant from an alternative donor. On the other hand, nonsplenectomized patients more often were transfusion dependent prior to transplantation.5 Without data from a large, prospective randomized trial, it is impossible to address the issue of the effect of pretransplantation splenectomy on transplantation for myelofibrosis with certainty. Such a trial is not currently available. From the present data it appears that, similar to the situation in patients not receiving transplants with agnogenic myeloid metaplasia and splenomegaly as reported by Tefferi et al,2 broad, general recommendations are difficult to formulate for patients who plan to receive a hemopoietic cell transplant. For now, the decision about splenectomy should be determined by patient symptomatology and not based on a presumed effect of splenectomy on posttransplantation outcome.
Zihai Li, Ted Gooley, Frederick R. Appelbaum, and H.
Joachim Deeg
References 1. von Bueltzingsloewen A, Bordigoni P, Dorvaux Y, et al. Splenectomy may reverse pancytopenia occurring after allogeneic bone marrow transplantation [letter]. Bone Marrow Transplant. 1994;14:339-340[Medline] [Order article via Infotrieve].
2.
Tefferi A, Mesa RA, Nagorney DM, Schroeder G, Silverstein MN.
Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients.
Blood.
2000;95:2226-2233
3.
Guardiola P, Anderson JE, Bandini G, et al.
Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European group for blood and marrow transplantation, Société Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center collaborative study.
Blood.
1999;93:2831-2838 4. Martino R, Altes A, Muniz-Diaz E, et al. Reduced transfusion requirements in a splenectomized patient undergoing bone marrow transplantation. Acta Haematol. 1994;92:167-168[Medline] [Order article via Infotrieve]. 5. Thomas ED, Clift RA. Allogeneic transplantation for chronic myeloid leukemia. In: Thomas ED,Blume KG,Forman SJ, eds. Hematopoietic Cell Transplantation. 2nd edition. Boston, MA: Blackwell Science; 1999:807-816.   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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