With modern consolidation treatment about 60–80% of younger and 20–30% of older patients with de novo acute myeloid leukemia (AML) who achieve a first hematological remission enjoy a long-term remission and are possibly cured. 1 2 Patients who relapse after chemotherapy (CT) have a definite chance to achieve a second remission after treatment with intensive CT. 3 4 5 We and others 6 7 have shown that the probability of a second CR depends mainly on the duration of the first remission.
Can AML relapse?
AML can relapse if: The cancer didn't respond well to the first treatment you tried. Treatment didn't get rid of all the leukemia cells. Cancer cells spread to other parts of your body and were too small for tests to pick up.
Can acute myeloid leukemia (AML) go into remission?
Most often, acute myeloid leukemia (AML) will go into remission after the initial treatment. But sometimes it doesn't go away completely, or it comes back (relapses) after a period of remission. If this happens, other treatments can be tried, as long as a person is healthy enough for them.
What is the treatment for relapse of FLT3-ITD mutated AML after SCT?
Sorafenib and azacitidine as salvage therapy for relapse of FLT3-ITD mutated AML after allo-SCT. Eur J Haematol. 2017; 98:348–354.
What is the treatment of choice for elderly AML?
Nonintensive therapy is the treatment of choice for elderly AML patients or patients with significant comorbidities. Since the approval of decitabine and azacitidine in AML, HMAs have become the standard of care for elderly AML patients.
How many times can you go into remission with AML?
About 2 out of 3 people with AML who get standard induction chemotherapy (chemo) go into remission.
How long can you live with secondary AML?
According to one population-based study, median survival among patients with secondary AML is estimated to be only 6 to 12 months, even with treatment with intensive standard chemotherapy.
How many times can leukemia relapse?
Overall, about 10 to 20 percent of people with ALL will have a relapse. This typically happens within 2 years of initial treatment. Adults with ALL are more likely (50 percent) to experience a relapse than children (10 percent).
Can leukemia go into remission twice?
If remission lasted at least a year, it's sometimes possible to put the leukemia into remission again with more chemo, although this is not likely to be long-lasting.
Can secondary AML be cured?
Secondary AML can be more complicated to treat than primary AML. But with combination chemotherapy drugs and stem cell transplants, as well as new treatments under investigation, it's possible to achieve and maintain remission.
Is secondary AML curable?
With the exception of secondary acute promyelocytic leukemia, the prognosis of which does not differ from very good prognosis of the primary forms, secondary AML is not considered a conventionally curable disease.
How long can you live after leukemia relapse?
The median survival after relapse was 4.5 months (95% CI, 4–5 months).
Is relapsed ALL curable?
Patients with relapsed ALL remain curable despite the failure of the initial course of treatment. The treatment strategies for adult patients with ALL are similar to those for children with ALL. The mainstay of the treatment for relapse ALL is chemotherapy, often given with steroids to improve the effectiveness.
What happens when you relapse leukemia?
Patients who relapse in their marrow during or just after completing initial treatment may benefit from a stem cell transplant. Patients who relapse six months or more after initial treatment can often be re-treated with more intensive chemotherapy without a transplant. Relapses most often occur in the bone marrow.
Can you survive AML relapse?
Patients with AML that relapses after an initial complete remission can be cured with autologous stem cell transplant. Many centers have reported cure rates of 25-50% for patients with AML transplanted in second remission or early in first relapse.
How often does AML relapse?
AML relapse affects about 50% of all patients who achieved remission after initial treatment, and can occur several months to several years after treatment. However, every patient carries the risk of relapse, and the majority of relapses occur within two to three years of initial treatment.
Why does AML relapse?
AML can relapse if: The cancer didn't respond well to the first treatment you tried. Treatment didn't get rid of all the leukemia cells. Cancer cells spread to other parts of your body and were too small for tests to pick up.
For Most Types of Acute Myeloid Leukemia
If acute myeloid leukemia (AML) doesn’t go away with the first treatment, newer drugs or more intensive doses of chemotherapy (chemo) drugs may be...
For Aml With An IDH2 Gene Mutation
If the leukemia cells have an IDH2 gene mutation, one option if the leukemia doesn’t go away or if it comes back later might be treatment with a ta...
For Acute Promyelocytic Leukemia
For patients with acute promyelocytic leukemia (APL) who don’t respond to initial treatment with chemo plus ATRA or who relapse, arsenic trioxide (...
How to improve outcome in relapsed AML?
In order to improve outcome in relapsed AML, it will be important to intelligently combine novel substances with each other as well as chemotherapy in prospective clinical trials. The development of therapies with bispecific antibodies or chimeric antigen receptor T cells (CAR-T) are still in early development.
What is the therapeutic aim of hydroxurea?
For those patients that are unfit, the therapeutic aim is to prolong life with acceptable quality of life. Here, hypomethylating agents (HMA), low-dose AraC (LDAC), and solely cytoreductive therapy with hydroxurea are options depending on first-line therapy.
Is gilteritinib tolerated?
For patients with FMS-like tyrosine kinase 3 (FLT3) mutations, treatment with the selective FLT3 inhibitor gilteritinib is well tolerated and leads to improved outcome compared with standard salvage therapy. The approval has been granted by the FDA and the EMA.
Is venetoclax used in combination with salvage therapy?
For those patients that have not been treated with venetoclax in first line, the combination therapy of venetoclax with demethylating agents achieves encouraging response rates. Venetoclax is currently also studied in combination with intensive salvage therapy.
Is relapse a common symptom of acute myeloid leukemia?
Relapse is still a common scenario in acute myeloid leukemia (AML) treatment and occurs in 40-50% of younger and the great majority of elderly patients. The prognosis in relapsed AML patients is generally poor but depends largely on the timing of relapse (early versus late) and the possibility of allogeneic hematopoietic stem cell transplantation ...
Relapsed vs. refractory AML
The Leukemia & Lymphoma Society (LLS) notes that most people with AML achieve remission after first receiving treatment. However, other people may still have residual cancer cells that persist after AML treatment. If someone does not reach remission after two cycles of chemotherapy, doctors refer to their condition as refractory AML.
Statistics
Relapse is common among people with AML. According to a 2019 study in the Blood Cancer Journal, approximately two-thirds of people with AML relapse after their initial treatment. The likelihood of relapse varies among age groups, with 40–50% of younger people experiencing a relapse at some stage compared with the large majority of older people.
Symptoms of AML relapse
The symptoms of an AML relapse are similar to those that people may experience at the time of their initial diagnosis. According to the LLS, these symptoms can include:
Diagnostic factors
As in the initial diagnosis, doctors will consider a variety of factors when diagnosing a relapse and evaluating the person’s outlook. These factors include:
How to treat relapsed AML?
A bone marrow or stem cell transplant is another treatment for relapsed AML. First, you get high-dose chemotherapy to kill as many cancer cells as possible. Then you get healthy stem cells from a donor to replace the blood cells that chemo destroyed.
How Do You Know Your AML Has Relapsed?
One way to find out is to look for symptoms, which might be the same ones you had when you were first diagnosed.
How do you know if you have relapsed leukemia?
Your doctor will tell you that you've relapsed if the number of leukemia cells in your bone marrow has gone up and you have fewer healthy cells in your blood.
What to do if AML doesn't go away?
If your AML doesn’t go away with the first treatment, your doctor may recommend newer drugs or more intensive doses of chemotherapy. If AML has spread to your brain and spinal cord, you may get the chemo straight into your spinal fluid. A procedure called a lumbar puncture uses ...
What is the goal of AML?
The goal of acute myeloid lymphoma (AML) treatment is to put you into remission -- when you have no leukemia cells found in your blood or bone marrow and you have no symptoms of the disease. Most people who are treated go into remission, but it doesn't always last. A relapse means that your leukemia has come back.
What to do if AML keeps coming back?
If your AML doesn't improve with treatment or it keeps coming back, you may want to ask your doctor about clinical trials. These are studies that test new drugs, combinations of chemotherapy, or other treatments to see if they're safe and if they work.
Can AML relapse?
AML can relapse if: The cancer didn't respond well to the first treatment you tried. Treatment didn't get rid of all the leukemia cells. Cancer cells spread to other parts of your body and were too small for tests to pick up. AML can relapse months or years after your first treatment.
What is the treatment for AML?
Most people with AML receive chemotherapy treatments. These medications rapidly kill dividing cells, such as cancer cells. Chemotherapy can lead to remission, which means a person doesn’t have symptoms of the disease and their blood cell counts are in a normal range.
What effect does AML type have on survival rate?
Doctors often classify the different types of AML by their cell mutations. Some cell mutation types are known to be more responsive to treatments. Examples include mutated CEBPA and inv (16) CBFB-MYH11 cells.
What is AML in medical terms?
What is acute myeloid leukemia (AML)? Acute myeloid leukemia, or AML, is a type of cancer that affects the bone marrow and blood. It’s known by a variety of names, including acute myelogenous leukemia and acute non-lymphocytic leukemia. AML is the second most common leukemia type in adults. Doctors call AML “ acute ” because ...
Why is AML called acute?
Doctors call AML “ acute ” because the condition can progress rapidly. The term “ leukemia ” refers to cancers of the bone marrow and blood cells. The word myeloid, or myelogenous, refers to the cell type it affects. Myeloid cells are precursors to other blood cells.
How many people go into remission after chemo?
Around 90 percent of people with an AML type known as acute promyelocytic leukemia (APL) will go into remission after “induction” (first round) of chemo. This is according to the American Cancer Society (ACS). For most other types of AML, the remission rate is around 67 percent.
How many years of AML will a child survive?
AML will return in some cases. The five-year-survival-rate for children with AML is 60 to 70 percent.
Why do people lack RBCs?
That’s because their body is too busy making the leukemic blast cells.
Risk factors
Below are some factors that can increase the risk of developing another cancer for someone with AML:
Symptoms of breast cancer
Research has found that people who survive breast cancer have a higher risk of developing AML as a second cancer. Conversely, breast cancer can develop as a second cancer in people with AML.
Symptoms of oral and pharyngeal cancer
People with AML in remission who are under 60 may have a higher risk of developing oral and pharyngeal cancer. Symptoms of this disease include:
Symptoms of colorectal cancer
People over 60 with AML in remission may have an increased risk of colorectal cancer. Colorectal cancer symptoms include:
Symptoms of lung cancer
The American Cancer Society lists the following symptoms of lung cancer:
What is the treatment for AML after chemo?
Allogeneic HSCT is the treatment of choice for AML patients relapsing after chemotherapy. Transplant eligibility depends on patients’ age as well as comorbidities (eg, as calculated by the Hematopoietic Cell Transplantation-specific Comorbidity Index15). Thus, in case not already done at the time of diagnosis, human leukocyte antigen (HLA) typing should be performed in all transplant-eligible patients at time of relapse. Prior to allogeneic HSCT, salvage therapy is necessary, especially for patients with high blast percentage in the bone marrow. A subgroup of patients (eg, those unlikely to benefit from salvage therapy) who have primary refractory disease might benefit from direct allogeneic HSCT.7Several intensive treatment protocols are established as salvage therapy. Anthracyclines and high-dose cytarabine are usually the backbone of these salvage regimens. Examples of commonly used regimens include Fludarabine, Cytarabine, Idarubicin, and granulocyte-colony stimulating factor (FLAG-IDA) and Mitoxantrone, Etoposide, and Cytarabine (MEC). Expected CR rates with these regimens are around 29%–66%.16None of these regimens have shown superiority over the others, again highlighting how little progress has been made over the years.17CR rates of r/r AML patients with salvage therapy are considerably lower as compared to rates achieved in front-line treatment.6Furthermore, remissions are usually not long sustained, making allogeneic HSCT a critical element for cure. The combination of these salvage regimens with novel drugs is currently under investigation. In 2 smaller studies, venetoclax, an oral highly selective small-molecule B-cell leukemia/lymphoma-2 inhibitor, was combined with the intensive salvage regimen FLAG-IDA. In our observational study, 13 r/r AML patients received FLA-V-IDA (FLAG-IDA plus venetoclax given on days 1–7).18The outcomes of these 13 FLA-V-IDA patients were retrospectively compared to 81 r/r AML patients treated with conventional FLAG-IDA. Importantly, the addition of 7-day venetoclax did not result in excess hematological toxicity. The overall response rate (ORR) was 69% in patients treated with FLA-V-IDA versus 47% in patients treated with FLAG-IDA.18In a similar phase Ib/II study, FLAG-IDA was combined with venetoclax. Initially, patients received a 21-day course of venetoclax.19However, after observing sepsis or bacteremia in 5 of 6 patients, the schedule of venetoclax was reduced to a 14-day course. Twenty-six out of 35 (74%) r/r AML patients achieved an overall response (CR/CR with incomplete hematologic recovery [CRi]/CR with partial hematologic recovery) and 54% achieved CR/CRi.19Both studies, despite being small and early, are encouraging for the combination therapy. CPX-351, the liposomal formulation of daunorubicin and cytarabine, has also been studied in r/r AML patients. In a phase II trial, 125 r/r AML patients were randomized 1:2 to receive conventional salvage therapy or CPX-351.20One-year survival was similar in both treatment arms. Interestingly, in the subset of patients with poor-risk cytogenetics, CPX-351 demonstrated higher response rates (39.3% versus 27.6%) and improved overall survival (OS) (hazard ratio [HR], 0.55; P= 0.02). However, to date, CPX-351 has no approval in the r/r setting. Instead, CPX-351 has received approval as front-line treatment for patients with s-AML, t-AML, as well as AML with MRC. These examples demonstrate how novel agents can be added to established salvage therapies. Nevertheless, further studies are highly needed in order to understand how novel agents can be combined with each other or with standard therapy in r/r AML to improve outcome of r/r AML.
What is salvage therapy for acute myeloid leukemia?
Salvage therapy is given in order to reduce the leukemia load prior to transplantation. Patients achieving complete remission prior to allogeneic HSCT have a more favorable outcome. Intensive salvage regimens commonly consist of an anthracycline and high-dose cytarabine backbone. Donor lymphocyte infusions have shown efficacy in patients relapsing after allogeneic HSCT. For patients who cannot be intensively treated (eg, elderly AML patients), outcome is generally very poor and combinations with novel agents are currently under investigation. Mutational analysis should be repeated at the time of relapse to identify aberrations that can be targeted with new agents. For r/r AML patients with mutated fms-related tyrosine kinase 3(FLT3), gilteritinib has shown superior results to intensive salvage regimens. The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved gilteritinib for FLT3mutated r/r AML patients. Ivosidenib and enasidenib, inhibitors for mutated isocitrate dehydrogenase(IDH) 1 and 2, respectively, have received approval for IDH1/IDH2mutated r/r AML by the FDA (not EMA). APR-246 restores the function of mutated TP53and early study results are promising. Other agents targeting CD47, menin, neural-precursor-cell-expressed developmentally down-regulated 8, as well as bispecific antibodies or chimeric antigen receptor T cells are under investigation. Further trials are needed to understand how to best combine novel agents with each other or with chemotherapy.
What is MRD assessment?
Measurable residual disease (MRD) assessment prior to allogeneic HSCT has demonstrated that a lower leukemia burden has been associated with a more favorable outcome after allogeneic HSCT,21,22emphasizing the significance of effective salvage therapy. In the setting of r/r AML, allogeneic HSCT is mostly performed from matched related as well as unrelated donors in the United States and in Europe. However, haploidentical donors have become good alternatives due to advancement in prophylaxis of graft-versus-host-disease, for example, application of post-transplantation cyclophosphamide.23Early data suggests that MRD-positive patients show a lower relapse rate if transplanted from a haploidentical versus a matched related/unrelated donor.24Prospective trials addressing this question are currently underway and will hopefully give us future guidance. In general, allogeneic HSCT achieves survival in 20%–35% of these patients at 4 years.12,13Thus, relapse after allogeneic HSCT is a common problem and occurs in 25%–55% of AML patients.14
Why is clonal diversity important in AML?
Clonal diversity and evolution is an important driver of r/r AML. While some mutations are stable and remain present at diagnosis and relapse, other mutations can be lost or gained so that the molecular profile at diagnosis and relapse can differ. Due to prognostic and therapeutic implications, it is recommended to repeat mutational profiling at the time of relapse.
Is azacitidine a nonintensive treatment?
Nonintensive therapy is the treatment of choice for elderly AML patients or patients with significant comorbidities. Since the approval of decitabine and azacitidine in AML, HMAs have become the standard of care for elderly AML patients. In a phase III trial with 488 elderly AML patients, azacitidine improved median OS from 6.5 to 10.4 months with conventional treatments (eg, LDAC).26Outside clinical trials, treatment with HMAs was associated with a median OS of 7–8 months.27
Is relapse a good prognosis for AML?
Prognosis is very poor for those patients with post-allograft relapsed AML, that is, relapsing after allogeneic HSCT. Unfortunately, this is a common clinical scenario given the relatively high relapse rate described above. The 2-year OS of relapsed patients following allogeneic HSCT ranges between 14% and 25% with even fewer of them achieving a long-term cure.14There is no established standard therapy for patients with post-allograft relapse, and continued research is urgently needed in order to improve their dismal outcome. Importantly, a second HSCT is associated with markedly higher transplant-related mortality as the first transplantation.25Donor lymphocyte infusions (DLIs) may represent an alternative strategy to second allogeneic HSCT as DLIs can also achieve a graft-versus-leukemia (GvL) effect. A retrospective registry study in relapsed AML patients compared the effect of DLIs versus second HSCT.25In the study, 137 patients were treated with a second HSCT while 281 patients received a DLI. Both interventions achieved better outcome if applied after achieving CR and dismal outcome if applied in patients relapsing less than 6 months after initial transplant. OS was comparable for patients treated with DLIs and second HSCT, with a 2-year OS of 25% versus 26%, and 5-year OS of 15% versus 19%, respectively.
Is venetoclax approved for elderly?
For these patients, outcome is generally very grim. In this context, the approval of venetoclax for elderly AML patients by the US Food and Drug Administration (FDA) in 2018 (with European Medicines Agency [EMA] approval still pending) has positively changed the treatment landscape for elderly AML patients. Approval was based on the encouraging results of venetoclax in combination with LDAC5and HMAs.4Fifty-four percent of AML patients treated with venetoclax and LDAC achieved either a CR or CRi with a median OS of 10.1 months.5For patients who received this combination front-line (ie, without prior HMA exposure), CR/CRi rates were 64% with a median OS of 13.5 months.5In a randomized trial comparing HMAs in combination with venetoclax or placebo, median OS was 14.5 months in the venetoclax arm compared to 9.6 months in the placebo arm. Furthermore, the CR/CRi rate was increased from 28.3 in the placebo arm to 66.4 in the venetoclax arm. Response and durable remission have been associated with mutations in NPM1and isocitrate dehydrogenase(IDH) 2while mutations in FLT3, RAS, and biallelic TP53mutations are increased in patients refractory to venetoclax.29Many elderly patients (especially in the United States, and likely soon more globally) will have received venetoclax combinations front-line. As these combinations are relatively novel, we still lack comprehensive and long-term data of patients relapsing after initial venetoclax combinations. However, a retrospective analysis suggests that once patients become r/r to HMA/venetoclax, the prognosis is dismal.30Importantly, in this setting, salvage therapy seems to be ineffective as patients who receive salvage therapy after HMA and venetoclax failure showed a median OS of only 2.9 months30as compared to 9.5 months when being r/r to HMA alone as previously reported.31This suggests a very aggressive disease biology arising after HMA/venetoclax failure. This is supported by the observation that patients with favorable predictive markers (eg, mutations in IDH1/2or NPM1) at the initiation of treatment developed high-risk cytogenetic and molecular features (eg, mutations in TP53, N/KRAS, and/or KIT) when being r/r to HMA/venetoclax.30In elderly patients who fail HMA/venetoclax, the first choice of salvage treatments are clinical trials and targeted approaches, which are described below. Of note, r/r AML patients who are venetoclax-naive may benefit from venetoclax treatment as second- or third-line treatment, but not as single agent as it has no significant activity as monotherapy.32In a single-center retrospective study, 33 patients with r/r AML (20 patients who failed HMA, 13 patients who relapsed after allogeneic HSCT) were treated with HMA and venetoclax.33ORRs were 64%, with 30% of patients achieving a CR, 21% a CRi, and 12% a morphological leukemia-free state (MLFS). Importantly, the best response was obtained after 2 cycles of therapy, which is more rapid as compared to HMA alone.33Response rates were similar between patients with prior allogeneic HSCT or HMA therapy. Further retrospective studies involving between 21 and 90 r/r AML patients have also studied venetoclax in combination with HMA/LDAC.34–37Here, CR rates were between 38% and 46% with a median OS of 5.6 to 7.8 months.34–37In a prospective trial, venetoclax was added to a 10-day schedule of decitabine.38Fifty-five of 168 AML patients (33%) in the trial had r/r AML. The ORR was 62% in this cohort of patients (34/55 patients). A frequent side effect was febrile neutropenia, occurring in 29% of patients. The median OS was 7.8 months in r/r AML patients as compared to 18.1 months in newly diagnosed AML patients.38These early data suggest that venetoclax combinations may also play a role in the r/r setting, but are unlikely to lead to long-term remissions or cure.
Acute myeloid leukaemia (AML) relapse
For some patients having intensive treatments, and for all having non-intensive treatment, there’s a risk of relapse.
Information for young adults
For young adults with leukaemia, lymphoma or any blood cancer type. Your guide to treatment, side effects, coping with emotions, friends and work or study.
Relapse treatment
The treatment for relapsed AML varies from patient to patient. Before you have any treatment, you’ll discuss your options with your healthcare team to find the best treatment for you. Lots of different factors can influence which treatment you have, including your age, your medical fitness, and how long you were in remission for.
Palliative care in relapse
If the doctors feel that more treatment isn’t likely to succeed, you may be advised that palliative care is more appropriate than intensive treatment. Your doctor will discuss the options with you in detail before you decide on a treatment plan.