Continuous Complete Remission in Two Patients with Acute Lymphoblastic Leukemia and Severe Fungal Infection Following Short-Term, Dose-Reduced Chemotherapy

Abstract

Spontaneous remission in acute lymphoblastic leukemia (ALL) is a rare phenomenon, which typically involves a pattern of feverish or septic disease followed by quick but mostly transient remission. We report on two male patients (46-year-old (pt. 1) and 19-year-old (pt. 2)) with CD20 positive, BCR-ABL negative common B-ALL. Patient 1 had received dexamethasone and cyclophosphamide (1.2 g) as a prephase therapy, followed by rituximab and a cumulative dose of 200 mg daunorubicin combined with 2 mg vincristine as an induction therapy. Patient 2 was treated with a reduced therapy regimen (Vincristine 1 mg, dexamethasone and 80 mg daunorubicin, 12-month mercaptopurine maintenance) due to (alcohol-related) toxic liver failure and pontine myelinolysis. Both patients developed severe septic disease just few days into induction treatment. Patient 1 suffered from pulmonary mycosis, which had to be resected eventually. Histological work-up revealed invasive mucor mycosis. Patient 2 presented with elevated serum aspergillus antigen and radiographic pulmonary lesions, indicative of pulmonary mycosis. In both patients, chemotherapy had to be interrupted and could not be resumed. Both patients recovered under broad antimicrobial, antifungal and prophylactic antiviral therapy and achieved molecular complete remission. At data cut-off remissions had been on-going for 34 months (pt. 1) and 8 years (pt. 2). Short-term, reduced intensity induction chemotherapy accompanied by severe fungal infections was followed by long-lasting continuous complete remissions in ALL. Thus, we hypothesize that infection-associated immunogenic responses may not only prevent early relapse of ALL but could also eradicate minimal residual disease. The effects of combined cytotoxic therapy and severe infection may also be mimicked by biomodulatory treatment strategies aiming at reorganizing pathologically altered cellular signaling networks. This could reduce toxicity and comorbidity in adult patients requiring leukemia treatment. Therefore, these two cases should encourage systematic studies on how leukemia stroma interaction can be harnessed to achieve long lasting control of ALL.

Acute Lymphoblastic Leukemia cured without treatment – is That So?

“…This cytotoxic reaction involving γδT cells, which may cause a reduction of leukemic clones and, consequently, eradicate MRD and prevent future relapse, can be triggered by acute infection. This, in turn, might explain why these temporary SR were described in patients presenting with fever [19,20]. Although this patient had two isolated febrile peaks, they were selflimited and associated with IgEV and platelets pool infusions.…”

Apoptosis as Driver of Therapy-Induced Cancer Repopulation and Acquired Cell-Resistance (CRAC): A Simple In Vitro Model of Phoenix Rising in Prostate Cancer

“…Recently, anakoinosis was proposed as a successful way of modulating cancer tissue homeostasis by re-establishing a new equilibrium via "tissue editing" [50]. Pro-anakoinotic drugs act as tissue master modulators, thereby preventing tissue defenses, providing a concerted regulative activity profile of a treatment schedule's single components, and may facilitate long-term tumor control or even continuous complete remission [51][52][53][54]. Importantly, this approach showed that classic pro-apoptotic drugs are un-necessary to induce long-term tumor control or continuous complete remission [55]: anakoinosis would thus bypass the intrinsic limitation of the current pro-apoptotic therapies by aiming at bio-modulation instead of cytotoxicity, possibly avoiding CRAC as suggested by in silico modeling [56].…”

Case Report: Spontaneous remission of early T-cell precursor acute lymphoblastic leukemia

“…Reports of spontaneous remissions of ALL have shown periods of temporary remission varying in duration from 14 days to 8 years. 16,17 It should be noted that the longest periods of remission are generally with patients who had SR but also received therapy.…”