Autologous Bone Marrow Transplantation - Blog Science Connections

66 ABMT in Acute Nonlymphocytic Leukemia
jLig/ml of 4-HC does not interfere with reasonably prompt hematologic
reconstitution after infusion of drug-treated marrows in patients with leukemias
and lymphomas (9,10). However, aplasia occurred in three of seven patients
who received autologous marrow treated with 120 ug/m\ of 4-HC, suggesting
that that dose of 4-HC was toxic to normal human hematopoietic stem cells
(10).
Exposure to 4-HC substantially inhibits the growth of committed (10,24)
and multilineage (24) human hematopoietic progenitor cells in vitro, though
more primitive blast cells may be less sensitive to the drug (25). In our study, the
number of CF(Js-GM infused in 4-HC-treated marrows was greatly reduced, but
hematologic reconstitution nevertheless occurred in 32 of 33 évaluable
patients. The time to recovery of neutrophil and platelet counts in recipients of
4-HC-treated marrow was significantly slower than time to hematologic
reconstitution in recipients of untreated allogeneic or syngeneic marrow.
However, similar delays in recovery of leukocytes and platelets have been
described in patients undergoing ABMT for acute leukemia with untreated
(26,27) or drug-incubated (28-30) marrow. Persistent thrombocytopenia (for 4
to more than 10 months after ABMT) was noted in several patients, a finding
similar to that reported for recipients of untreated marrow autografts for ANLL
in first remission (27). It is not known whether these patients have had damage
to the megakaryocytopoietic stem cell population or have a poorly compensated
thrombocytolytic state after autologous marrow transplantation. On balance,
the hematopoietic toxicity observed after marrow treatment with 4-HC appears
acceptable and is similar to that seen in patients receiving intensive remissioninduction
chemotherapeutic regimens in acute leukemia (1 -3).
Twelve of the 40 patients (30%) died of nonleukemic causes. Eight deaths
were attributable to bacterial or fungal sepsis during aplasia, a frequency much
higher than that reported after allogeneic (7,31) or syngeneic (17) BMT for
ANLL. Two deaths from sepsis with Pseudomonas aeruginosa occurred about
the same time and were owed to a strain of that organism resistant to multiple
drugs, and one death from gram-negative sepsis occurred in the context of
neutropenia and persistent marrow hypoplasia. The occurrence of fatal
interstitial pneumonitis (one cytomegalovirus, one idiopathic) is similar to that
seen in syngeneic marrow transplant recipients (32) and is much less frequent
than in allogeneic transplant recipients (4-7). Hepatic veno-occlusive disease, a
well-recognized complication of marrow transplantation (33), was fatal in two
patients, both in third remission at the time of marrow transplantation.
Hepatotoxicity from previous chemotherapy, infectious agents, or both may
have predisposed these patients to this complication (33). The prospective
identification of and particular attention to those patients at high risk for these
kinds of posttransplantation complications may further improve survival after
ABMT.
This study demonstrates that intensive antileukemic therapy followed by
autologous transplantation with 4-HC-treated marrow may be associated with