Reflecting on Treatment Strategies for Acute Leukemia

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Leukemia is sometimes a solid, metastatic, and invasive neoplasm, but this is forgotten when leukemia is viewed as only a “liquid” cancer.
Leukemia is sometimes a solid, metastatic, and invasive neoplasm, but this is forgotten when leukemia is viewed as only a “liquid” cancer.

War starts only after its strategist maps out where the enemy is obvious and where it can hide. This is the strategy of every oncologist planning assault on cancer.

Every cancer, except acute leukemia. Though taught by pathologists a century ago that leukemia is sometimes a solid, metastatic, and invasive neoplasm, this is forgotten when leukemia is viewed as only a ”liquid” cancer. It is not confined to marrow if its hiding sites are not documented to be empty.

We don't look for them. Although chemotherapy achieves very high complete remission rates with initial exposure, there remain very high rates of relapse and poor prognosis for most subtypes. Relapse is too often accepted as the result of leukemic cells outsmarting our best drugs, without considering that the enemy may have emerged from places it hid, growing while chemotherapy floats by.

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Why overlook this possibility? Often, the marrow remains in remission when the chemoresistant tumor starts metastasizing, progressing independently and ultimately contaminating the marrow. Even when tumors present in a single site, systemic chemotherapy is often initiated, despite our knowledge that directed local treatment is why patients with testis and meningeal involvement may have long disease-free survival.

How can we ignore what pathologists taught us? There is a growing stream of published case reports of extramedullary relapse in various organs. They typically detail how a tumor presents and how it progresses to death.

Isabel Cunningham, MD
Isabel Cunningham, MD

Almost all tumors are recognized only when visible or symptomatic. The autopsy literature documents that clinical observation significantly underestimates their true incidence.

So, why do oncologists rarely employ the strategy that is used before attacking every other cancer, that of scanning? Leukemic tumors can be identified on gallium, MRI, CT, and PET scans, but without them, the only way to find occult tumors is autopsy. If we don't do scan or autopsy, the cause of any patient with leukemia's marrow relapse is unknown.

We have then fought his battle without the maps that are available. Why? The literature is full of cases of leukemic tumors appearing to be solid cancers on presentation, and cancer operations then performed have successfully aborted the metastatic potential of leukemic tumors in breast, testis, ovary, gallbladder, and small bowel.

It is likely that the removal of a tumor's hospitable microenvironment along with the tumor is essential. There are no data, beyond anecdotes, that this can be accomplished with current chemotherapy.

There may be intraoperative confusion when the presumed solid cancer is found to be of hematologic origin. A surgeon is unlikely to excise a non-obstructing lymphoma, considering the likelihood it will respond to radiation and chemotherapy. Unlike lymphoma, leukemic tumors are generally chemoresistant.

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Whether radiotherapy, without excision, can permanently eradicate leukemic tumors and prevent metastasis has not been studied in tumors at the same site given the same doses. Radiation, like surgery, would only succeed if a tumor were truly isolated, which requires body scans. Systemic chemotherapy remains critical to protect the bone marrow, coordinated with local tumor eradication.

This editorial should not be taken as advocating scanning every acute leukemia patient at diagnosis. Its message is that we must stop the ‘liquid' view of leukemia and stay mindful of the thorough approach we give all cancers when facing inadequate or transient response.

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