Adult acute lymphoblastic leukemia



Overview

Definition

Adult acute lymphoblastic leukemia (ALL) is a common malignant hematological disease characterized by abnormal proliferation and aggregation of immature lymphocytes in bone marrow and lymphoid tissues.

Patients with chromosomal with (9;22)(q34;q11.2)/BCR-ABL1 recurrent genetic abnormality are called Philadelphia chromosome (Ph)-positive-ALL, otherwise Ph-negative-ALL.

ALL can be categorized into adult ALL and pediatric ALL, and this article refers specifically to adult ALL.

Disease types

There are three main criteria for ALL typing.

Cytomorphologic typing (FAB typing)

Mainly based on cytomorphology, it requires the proportion of primitive lymphocytes in the bone marrow to be more than 30%, and divides ALL into three subtypes: L1, L2, and L3.

Immunophenotyping

ALL can be broadly categorized into:

B-lineage ALL.

T-lineage ALL.

ALL with myeloid antigen expression.

WHO typing

The 2016 revised WHO classification on the main categories of ALL is as follows:

B lymphoblastic leukemia/lymphoma

T-lymphoblastic leukemia/lymphoma

Provisional typing: early pre-T-cell lymphoblastic leukemia.

Special reminder] The WHO classification is complex, and it is recommended to consult the physician for detailed information on the patient’s specific classification.

Incidence

Incidence rate

The incidence rate of leukemia in China is (3~5)/100,000, and acute leukemia is more common than chronic leukemia.

ALL accounts for 15% of all leukemias and about 30% of adult acute leukemias.

Prevalent population

Among acute leukemias, ALL is more common in children.

It is usually slightly more common in males than females.

Elderly ALL accounts for about 16% to 30% of adult ALL.

Causes

Causative factors

The exact cause of ALL is unknown, but leukemia in general may be associated with the following factors.

Infections

A variety of retroviruses such as avian leukemia virus (ALV), murine leukemia virus (MLV), feline leukemia virus (FeLV), gibbon ape leukemia virus (GaLV), and reticuloendothelial tissue proliferating virus (REV) can cause leukemia.

In the Burkitt’s lymphoma/leukemia endemic area of equatorial Africa, EBV (Epstein-Barr virus) infection has been shown to be associated with leukemia causation.

Human T-cellophilic virus type I (HTLV-I) is a causative factor in adult T-cell lymphoma/leukemia.

Radiation Factors

Ionizing radiation such as X-rays and gamma rays are leukemogenic, with a higher incidence in areas exposed to higher doses of radiation.

The probability of secondary leukemia is significantly higher in patients requiring radiation therapy for malignant tumors and certain benign diseases (e.g., seronegative ankylosing spondylitis, etc.) than in the general population.

In the past, the incidence of leukemia among medical personnel engaged in radiological diagnosis and treatment was relatively high, but with the improvement of protective measures, the incidence has been basically the same as that of the general population.

Chemical factors

Benzene: the incidence of leukemia in benzene-exposed individuals is 2 to 4.5 times that of the normal population.

Anti-tumor drug alkylating agents: The risk of leukemia is significantly higher in those who apply anti-tumor drug alkylating agents (nitrogen mustard, nitrogen mustard phenylbutyrate, cyclophosphamide, marfan, carmustine, lomustine, etc.) or topoisomerase II inhibitors.

Genetic factors

Although leukemia is not a hereditary disease, a monozygotic twin in which one partner develops leukemia within 6 years of age has a 25% likelihood of the other partner developing leukemia.

The incidence of leukemia in first-degree relatives of leukemia patients is three times that of the general population.

The incidence of acute leukemia in patients with Down syndrome is 10 times higher than in the general population.

Other Blood Disorders

Certain blood disorders may eventually develop into leukemia, such as myelodysplastic syndromes (MDS), lymphoma, multiple myeloma, and paroxysmal sleep hemoglobinuria (PNH).

Pathogenesis

The pathogenesis of ALL is unknown, but leukemogenesis may be multistep, and it is currently believed that at least two types of molecular events are involved in the development of the disease, the so-called “second-strike” theory.

Symptoms

The onset of acute leukemia varies. In acute cases, there may be a sudden high fever, similar to a “cold”, or there may be severe bleeding.

In slower cases, the disease is often detected when the patient seeks medical attention because of pallor, purpura, heavy menstrual periods, or bleeding that is difficult to stop after a tooth extraction.

Major Symptoms

The main symptom is the suppression of normal bone marrow hematopoiesis.

Anemia

Anemia is one of the most common symptoms of leukemia, which often appears earlier and worsens with the progression of the disease, but some patients may have no anemia due to the short course of the disease.

The main manifestations are pallor, weakness, dizziness, palpitation, anorexia and edema.

Fever and infection

More than half of the patients start with fever, which may be low or high. High fever can reach 39～40℃ or above, accompanied by chills and sweating.

Although leukemia itself can be febrile, high fever often suggests secondary infection.

Infections can occur in all parts of the body, with stomatitis, gingivitis, and pharyngitis being the most common, and ulceration or necrosis can occur.

Lung infections, perianal infections, and perianal abscesses are also common, and in severe cases, bloodstream infections may be present.

Bleeding

Bleeding is also a common manifestation, about half of the patients can have different degrees of bleeding.

Bleeding sites are widely distributed, with skin and mucous membranes being the most common, manifested as skin petechiae, ecchymosis and nosebleed, gum bleeding, etc.

Intracranial hemorrhage, gastrointestinal hemorrhage, and urinary tract hemorrhage, although relatively rare, often lead to serious consequences.

Bleeding from the fundus of the eye can lead to visual impairment, and in severe cases, widespread bleeding throughout the body occurs due to complications of coagulation abnormalities.

Headache, vomiting, asymmetrical pupil size, and even coma and death may occur in intracranial hemorrhage.

Other symptoms

Generally a series of manifestations of proliferative infiltration of leukemia cells.

Enlargement of liver, spleen and lymph nodes

Mild or moderate hepatosplenomegaly is common, giant spleen is rare.

Lymph node enlargement is common, and about half of the patients can be found to have enlarged lymph nodes at the time of consultation, which can involve superficial or deep lymph nodes such as mediastinum, mesentery and retroperitoneum.

Bone and joint pain

Bone pain is caused by leukemic infiltration of bone and periosteum [more common in children than in adults, more common in ALL than in acute myeloid leukemia (AML)].

Bone pain is often severe and variable in location, mainly in the limb bones, spine and pelvis, with a less pronounced wanderlust, and the application of common analgesics is ineffective.

More than 1/3 of patients have sternal pressure pain, which is one of the common signs of leukemia (helps in diagnosis).

A few patients may have bone marrow necrosis, which can lead to severe bone pain.

Central nervous system symptoms

It is the most common site of extramedullary infiltration in leukemia, with infiltration sites occurring in the arachnoid and dura mater, followed by the brain parenchyma, choroid or cranial nerves.

In mild cases, headache and dizziness are manifested.

In severe cases, there are nausea, vomiting, blurred vision, neck stiffness, and even convulsions and coma.

Other manifestations and hazards include facial paralysis or progressive paraplegia.

Testicular Symptoms

Testicular leukemia is second only to central nervous system leukemia (CNSL) as a source of extramedullary relapses of leukemia and is also frequently seen in patients with ALL in remission.

The main manifestations: painless enlargement of the testis, hard and non-tender; mostly one-sided, with no enlargement on the other side.

Mostly painless enlargement of testis on one side and no enlargement on the other side.

Leukemia can infiltrate other tissues and organs, such as lungs, heart, digestive tract, genitourinary system can be involved.

Other infiltration symptoms

Leukemia infiltration can also involve various tissues and organs such as lungs, pleura, kidneys, digestive tract, heart, brain, uterus, ovaries, breasts, parotid glands and eyes.

The above infiltrations may present with dysfunction of the corresponding organs, but may also manifest without symptoms.

Consultation

Recommendations

Acute lymphoblastic leukemia is mainly diagnosed and treated in the Department of Hematology, Department of Oncology or Leukemia Clinic.

It is recommended to consult a doctor when the patient develops symptoms such as unexplained fever, anemia, bleeding, bone pain, enlarged liver and spleen lymph nodes, fatigue, night sweats and weight loss.

Preparation for Consultation

Register

Before visiting the outpatient clinic, you need to register at the hospital or through official channels (such as the hospital’s official website, official app, 114 platform, etc.).

Emergency admissions can be made directly by registering. Pre-hospital emergency admissions generally do not need to register in advance, and can be made up in the course of treatment.

Preparation of documents

Prepare your medical card, social security card (medical insurance card) and other documents.

Bring previous medical documents such as copies of medical records and examination reports.

If you are taking medication, prepare a list of medications.

What questions the doctor may ask

What are the symptoms?

How long have the symptoms lasted?

Is there any fatigue?

Any nosebleeds or bleeding gums?

Is there a fever? What is the highest degree?

Any bone pain?

Are you regularly exposed to organic volatiles such as formaldehyde and benzene?

Have you been tested? What are the results?

Have you been treated? What kind of treatment? What is the effect of treatment?

What kind of medication did you take? Do you have any allergies?

Questions you can ask your doctor

What is the disease?

What kind of tests do I need to do?

What treatment is needed?

What is the prognosis?

Are there any precautions to be taken?

Diagnosis

Diagnostic basis

Medical history

History of hematologic disorders, such as myelodysplastic syndromes (MDS) and myeloproliferative neoplasms.

History of specific treatments, including tumor radiotherapy and chemotherapy, etc.

Family history of hematologic diseases, etc.

Clinical Presentation

When a patient presents to the clinic, he or she may have the following major manifestations:

Fever: variable type of fever, and this fever is not effective after treatment with antibiotics, etc.

Anemia: progressive aggravation, common weakness, pallor, shortness of breath after activity, drowsiness, etc. On physical examination, different degrees of pallor of the face, nail beds, and conjunctiva of the eyelids are found.

Bleeding: it is a common early symptom, manifested as bleeding spots on the skin and oral mucosa, nosebleed is also more common, and there can also be gastrointestinal bleeding and blood in urine.

In patients with infiltration, lymph nodes and hepatosplenomegaly may be present.

Laboratory Tests

Blood picture

In addition to routine blood tests, a blood smear should be done for manual classification.

Most peripheral blood leukocyte counts are elevated, but they can be normal or decreased in a wide range from 0.1 × 10⁹/L to 1500 × 10⁹/L, with a median count of 12 × 10⁹/L.

When the white blood cell count is >100 × 10⁹/L, usually primitive and naïve cells are seen on blood smears, hemoglobin and red blood cells are decreased, and platelets show varying degrees of reduction.

Biochemical tests

Liver and renal function, lactate dehydrogenase (LDH), and electrolytes are mandatory.

Patients with a high leukocyte load may have increased blood uric acid and LDH levels.

Excessive blood calcium is seen in 0.5% of patients and is due to the production of parathyroid hormone-like proteins by leukemic cells and leukemia-infiltrating bone.

Coagulation function

Includes PT, APTT, TT, FIB, DD dimer, FDP.

The onset of leukemia can cause a decrease in prothrombin and fibrinogen, which can lead to prolonged prothrombin time and bleeding.

Cerebrospinal Fluid Examination

Cerebrospinal fluid examination is an important basis for the diagnosis of CNSL and must be accompanied by a centrifugal flap method in addition to routine and biochemical tests.

CNSL is diagnosed if the lumbar puncture is non-invasive and the white blood cells (WBC) are >5×10⁶/L and naïve cells are seen.

Cytochemical examination

Cytochemical staining is an important component of morphologic diagnosis. It can be used to differentiate AML from ALL.

It has been gradually replaced by immunophenotyping in recent years with the widespread development of flow cytometric immunophenotyping.

Immunologic examination

Immunological examination by flow cytometry is mainly used for the typing of acute leukemia and differential diagnosis of AML and ALL according to WHO criteria.

Cytogenetic and molecular biology tests

Chromosome G-banding or R-banding analysis

Karyotype analysis is performed by applying chromosome banding techniques to detect abnormal chromosome numbers and structural changes such as translocations, inversions and deletions in leukemia cells.

More than 90% of ALL have clonal chromosomal abnormalities. Chromosome number abnormalities and structural abnormalities, among which common chromosome structural abnormalities include t(1;19), t(12;21), t(9;22), 11q23 and so on.

FISH examination

Conditional FISH examination should include MLL rearrangement with isolated probes, iAMP21.

ETV6-RUNX1 (TEL-AML1), E2A-PBX1, BCR-ABL1 can be done optionally.

PCR genetic testing

Should include at least ETV6-RUNX1, E2A-PBX1, MLL-AF4, BCR-ABL1, SIL/TAL1, MEF2D rearrangement, ZNF384 rearrangement, TCF3-HLF, and IKZF.

Ph-like gene or mutation testing.

Imaging

Chest X-ray and abdominal ultrasound: may help to understand cardiac function and abdominal organs.

CT and MRI examination: to evaluate the head or thoracic and abdominal occupations, bleeding or inflammatory conditions, etc.

Differential Diagnosis

There are numerous subtypes of ALL, and in addition to differentiating each subtype from each other, it is also necessary to differentiate it from the following diseases.

Infectious mononucleosis

Similarities: both have clinical manifestations such as fever, superficial lymph nodes and hepatosplenomegaly.

Differences: these patients have no primitive lymphocytes in the bone marrow and peripheral blood, positive serum heterophilic agglutination test, and positive serum EBV antibody, which can be differentiated from ALL.

AML M0, M1 and acute mixed cell leukemia

Similarities: Clinical manifestations and signs are similar to those of ALL, and the cell morphology is difficult to distinguish.

Differences: The differentiation is mainly based on cell surface antigens.

Aplastic anemia and immune thrombocytopenia

Similarity: the blood picture of both may be confused with leukemia without leukocytosis.

Differences: However, the liver and spleen lymph nodes are not large in both, and the differentiation needs to be based on the characteristics of bone marrow morphology (presence or absence of abnormally increased leukemic cells), chromosomal examination, etc.

Chronic lymphocytic leukemia

Similarities: both present with increased lymphocytes, and may have enlarged liver, spleen and lymph nodes.

Differences: most of them have a mild clinical progression and mature lymphocytes predominate in bone marrow and peripheral blood, which can be differentiated from ALL by cellular immunophenotyping.

Young lymphocytic leukemia

Similarities: both present with elevated lymphocytes and may have enlarged liver, spleen and lymph nodes.

Differences: Most of them have a mild clinical progression, with predominantly mature lymphocytes in the bone marrow and peripheral blood, and more than 55% of naïve lymphocytes. It can be differentiated from ALL by cellular immunophenotyping.

Leukemia-like reaction

Similarities: The clinical manifestations of leukemia-like reactions are highly similar to those of leukemia.

Differences

Leukemia-like reactions are often complicated by severe infections, malignant tumors and other underlying diseases, and have the clinical manifestations of the corresponding primary diseases.

Platelets and hemoglobin are mostly normal. After the primary disease is controlled, the white blood cells return to normal.

Treatment

Treatment principle

Doctors will stratify the prognostic risk according to the patient’s typing results and clinical characteristics, and select and design a complete and systematic treatment program according to the patient’s wishes and financial ability.

Considering the therapeutic needs and to reduce the pain of repeated puncture, doctors usually recommend to keep the deep vein catheter.

The treatment of ALL is generally carried out in stages.

Stage 1: Induction therapy

The aim is to rapidly kill detectable leukemia cells and reduce the residual leukemia cells in the body, so as to achieve normalization of routine bone marrow examination (bone marrow smear classification or biopsy), i.e., complete remission (CR).

Stage 2: Post-remission treatment

Treatment in this stage mainly includes consolidation, intensive, maintenance therapy and extra-marrow leukemia control as well as hematopoietic stem cell transplantation.

The aim is to clear residual leukemia cells that cannot be detected by conventional examination methods in order to reduce relapse and strive for long-term survival.

General treatment

General treatment of ALL includes:

Urgent management of hyperleukinemia

When peripheral blood leukocytes are >100 × 10⁹/L, hydration must be given urgently to prevent complications such as hyperuricemia, acidosis, electrolyte disorders, and coagulation abnormalities.

Short-term pretreatment before chemotherapy can be used, and the commonly used drugs are dexamethasone with hydroxyurea.

Prevention of infection

Patients with leukemia are often accompanied by granulocytopenia or lack of granulocytes, and are prone to infections.

Strict bedside isolation should be carried out, and antibiotic treatment should be applied prophylactically when necessary.

Component blood transfusion support

Severe anemia can cause severe hypoxia, weakness and dizziness, chest tightness and shortness of breath after activity, and even fainting.

Treatment such as oxygenation and transfusion of concentrated red blood cells may be administered.

Blood product transfusion treatment

Patients accompanied by abnormal coagulation function can be infused with blood products such as fibrinogen, plasminogen complex and plasma to supplement the required coagulation factors and improve the bleeding symptoms.

Prevention of hyperuricemia nephropathy

Leukemia patients should drink more water during chemotherapy and alkalinize the urine appropriately.

When patients have oliguria, anuria and renal insufficiency, they should be treated as acute renal failure.

Correction of coagulation disorder

Patients can cause coagulation disorders due to thrombocytopenia or combined infection, and diffuse intravascular coagulation (DIC) can be complicated in severe cases. Coagulation time should be closely monitored, and coagulation factors should be supplemented appropriately.

Nutritional support

Leukemia is a serious consumptive disease, especially when chemotherapy and radiotherapy cause patients’ digestive tract mucous membrane damage and dysfunction.

Attention should be paid to nutritional supplementation to maintain water and electrolyte balance. Doctors usually give patients high-protein, high-calorie, easy-to-digest food, and nutritional supplementation via vein when necessary.

Treatment of Ph-negative ALL

Induction therapy

Treatment by age group

Patients aged <40 years: clinical trials are recommended; or multi-agent combination chemotherapy.

Patients aged 40 ≤ age < 60 years: enrollment in a clinical trial or multi-agent combination chemotherapy is possible.

Patients aged ≥60 years: enrollment in a clinical trial, or multi-agent chemotherapy, or glucocorticoid induction is possible.

Treatment regimen

Commonly used drugs

Vincristine (VCR) or vincristine.

Anthracyclines/anthraquinones: e.g. Zoerythromycin (DNR), desmethoxyzoerythromycin (IDA), adriamycin, mitoxantrone.

Glucocorticoids: e.g., prednisone, dexamethasone, etc.

VDP regimen: a regimen based on a base consisting of commonly used drugs.

VDCLP regimen: recommended regimen, generally composed of VDP combined with CTX and mentholase (L-Asp).

Special reminder] The above program is for reference only, the specific treatment needs to be personalized by a professional physician according to the actual situation of the patient.

Treatment after remission

In order to minimize recurrence and increase the survival rate, consolidated and intensive post-remission treatment should be started as soon as possible after the completion of induction therapy.

Doctors will judge whether allogeneic HSCT (allo-HSCT) is needed according to the patient’s risk grouping, and those who need allo-HSCT should actively search for a donor.

Patients <40 years old

Continue multi-agent combination chemotherapy, especially those with negative microscopic residual disease (MRD).

Also perform allo-HSCT, especially in MRD-positive, high white blood cell count patients with poor prognosis cytogenetic abnormalities in B-ALL and T-ALL.

Patients 40 ≤ age < 60 years old

Continue multi-agent combination chemotherapy, especially MRD negative.

Or consider allo-HSCT, especially MRD-positive, high white blood cell count patients with poor prognostic cytogenetic abnormalities B-ALL, T-ALL.

Patients aged ≥60 years

Including those who are not suitable for intense treatment (advanced age, poorer physical status, severe organ complications, etc.) may be considered for continuation of chemotherapy.

Maintenance therapy

In patients with ALL, maintenance therapy is generally required.

Basic regimen: 6-mercaptopurine (6-MP) + methotrexate (MTX), or thioguanine (6-TG) + MTX.

Special reminder] The above plan is for reference only, and the specific treatment needs to be personalized by a professional doctor according to the actual situation of the patient.

Treatment of Ph-positive ALL

Treatment of non-elderly Ph-positive ALL

Refers to the patient population aged <60 years old.

Induction of remission therapy

Once Ph/BCR-ABL1 positive ALL is confirmed by fusion gene (PCR method) or chromosomal karyotyping/fluorescence in situ hybridization (FISH), it is entered into the Ph-positive-ALL treatment sequence.

Tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, etc. can be added (or started on day 8 or 15, as appropriate) from the date of diagnosis.

For those with allo-HSCT conditions, HLA matching is performed and donors are actively sought.

It is also recommended to start lumbar puncture and intrathecal injection as early as possible to prevent CNSL.

Post-remission treatment

Post-remission therapy for Ph-positive ALL is in principle referenced to general Ph-negative ALL, but can be discontinued with the use of menatase (L-Asp).

Tyrosine kinase inhibitors (TKI)

TKI is preferentially recommended for continuous application until the end of maintenance therapy.

Patients who are not eligible for TKI application follow the treatment regimen for general ALL.

Hematopoietic stem cell transplantation

Patients with suitable donor can choose allo-HSCT and can be maintained with TKI after transplantation.

Patients without suitable donor continue multi-agent chemotherapy + TKI as planned.

Patients without suitable donor and trans-negative for BCR-ABL fusion gene can be considered for autologous HSCT and maintained with TKI after transplantation.

Maintenance therapy

Those treated with TKI

TKI-based maintenance therapy can be combined with vincristine (VCR), glucocorticoids.

or 6-MP and MTX.

Or combined with interferon.

Those who cannot adhere to TKI treatment

Maintenance therapy with interferon, can be combined with vincristine (VCR), glucocorticoids and/or 6-MP and MTX.

Or refer to Ph-negative-ALL for maintenance therapy.

Precautions

During the maintenance treatment, try to ensure a review every 3 to 6 months.

The review includes bone marrow image, quantification of fusion gene (BCR-ABL) and/or flow cytometry to detect microscopic residual disease.

Treatment of Ph-positive ALL in the elderly (age ≥60 years)

The treatment of elderly Ph-positive ALL, in principle, refers to the general elderly Ph-negative ALL, in combination with TKI.

TKI is preferentially recommended to be applied continuously until the end of maintenance therapy.

Prevention and treatment of CNSL

CNSL is one of the main root causes of ALL relapse, which seriously affects the efficacy of leukemia.

CNSL prevention

Early prevention of CNSL should be emphasized in any type of adult ALL.

Preventive measures may include: intrathecal chemotherapy; radiation therapy; high-dose systemic chemotherapy; and a combination of measures.

Treatment of CNSL

Pharmacotherapy: Patients with confirmed diagnosis of CNSL, especially those with more obvious signs and symptoms, are recommended to first undergo lumbar puncture and intrathecal injection of triple combination of methotrexate (MTX) + cytarabine (Ara-C) + dexamethasone.

Radiotherapy: chemotherapy drugs can be injected intrathecally until the cerebrospinal fluid white blood cell count is normal and the symptoms and signs improve, then radiotherapy (cranial + spinal radiotherapy).

Special reminder

Drug therapy, especially chemotherapy for cytotoxic drug therapy, in killing tumor cells at the same time, but also damage the normal body cells, the specific use must be under the guidance of a professional doctor to choose the appropriate program, and individualized treatment.

Hematopoietic Stem Cell Transplantation

Hematopoietic stem cell transplantation, referred to as stem cell transplantation, refers to injecting normal donor or autologous hematopoietic cells into patients to rebuild normal hematopoietic and immune functions after pre-treatment of patients with systemic irradiation, chemotherapy and immunosuppression.

According to whether the hematopoietic cells are taken from a healthy donor or from the patient himself, it can be divided into allo-HSCT and autologous hematopoietic stem cell transplantation.

Autologous HSCT

The donor for this type of stem cell transplant is the patient himself, who should be able to withstand high doses of chemoradiation and be able to mobilize a sufficient amount of hematopoietic stem cells that are not contaminated by tumor cells.

allo-HSCT

Donor selection

The first choice of donor is HLA-compatible siblings, followed by HLA-compatible unrelated donors, haplotype-compatible related donors, or umbilical cord blood stem cells.

If more than one HLA-matched sibling is available, a young, healthy, male, cytomegalovirus (CMV)-negative and erythrocyte blood group compatible individual is selected.

Hematopoietic Cell Collection

The donor should be a healthy person, need to be examined to exclude infectious, chronic systemic diseases and other unsuitable conditions for donation, and sign an informed consent form.

The process of hematopoietic stem cell donation is safe, does not lower the resistance of the donor, does not affect the health of the donor, and the collection tubes and other medical materials are not reused and do not spread diseases.

Frontier Treatments

Cellular immunotherapy

Chimeric antigen receptor T (CAR-T) cell therapy is a new anti-tumor immunotherapy technology with specific killing efficacy and controlled side effects.

CAR-T therapy is currently an optional method of tumor killing in addition to radiotherapy, in which CAR-T19, CAR-T20, and CAR-T22 expressing CD19, CD20, and CD22 have entered clinical trials.

CAR-T cell therapy has been applied to patients with clinically refractory recurrence and is expected to enter first-line treatment.

Novel drugs

Novel drugs that are currently in clinical trials are:

Monoclonal antibodies: rituximab (anti-CD20), alemtuzumab (anti-CD52) and epalizumab (anti-CD22), etc.

Bispecific antibodies: blinatumomab, a bispecific antibody construct combining anti-CD19 and anti-CD3 specificity, has been approved by the US FDA for the treatment of Ph-negative relapsed/refractory acute B lymphoblastic leukemia in adults.

Other novel drugs: FLT3 inhibitors, farnesyltransferase inhibitors, proteasome inhibitors, and short interfering siRNAs are also being studied and may become future treatments.

[Special reminder] Frontier treatment-related therapies or drugs may be in clinical trials, and it is recommended that eligible patients may choose the appropriate clinical trials in order to achieve better survival.

Chinese medicine treatment

Some Chinese medicine treatments or drugs may improve the condition in the clinic, and it is recommended to go to a regular medical institution and be treated under the guidance of a physician.

[Special Reminder

Secret prescriptions, biased prescriptions, folk remedies and other methods of treatment have no scientific basis, effectiveness, safety and other difficult to guarantee, is not recommended.

Prognosis

Survival rate

If ALL patients are not treated in time, the average survival period is only 3 months, but most of the patients can survive for a long time if they are treated in a standardized way.

[Special Reminder

Average survival and other statistical data are only used for clinical research, does not represent the specific survival of the individual, the patient’s individual survival needs to be combined with a variety of factors to determine, it is recommended to consult the physician.

Prognostic factors

Prognostic factors are factors that have an impact on the overall survival and quality of life of the patient.

Major factors of poor prognosis

The exact risk factors associated with poor prognosis in ALL, mainly include the following:

WBC: at diagnosis, a peripheral blood white blood cell (WBC) count ≥50 × 10⁹/L.

Infiltration status: at diagnosis, those who have developed CNSL or testicular leukemia.

Immunophenotype: T-ALL.

Unfavorable cytogenetic and molecular genetic features

Hypodiploidy with a chromosome number <45 (or DNA index <0.8).

t(9;22)(q34;q11.2)/BCR-ABL1.

t(4;11)(q21;q23)/MLL-AF4 or other MLL gene rearrangement.

t(1;19)(q23;p13)/E2A-PBX1 (TCF3-PBX1), Ph-like, iAMP21, IKZF deletion, TCF3-HLF and MEF2D rearrangements.

Bone marrow remission at the end of induction remission therapy

Bone marrow not in remission (≥20% primitive and naïve lymphocytes).

Induction of bone marrow not achieved complete remission with primitive and naïve lymphocytes >5%.

Levels of microscopic residual disease (MRD)

MRD ≥ 10-¹ early in induction remission therapy (d15-19) and ≥ 10-² after induction remission therapy (d33-d45).

or MRD ≥10-⁴ before the start of consolidation therapy (around week 12).

Prognostic risk grouping for adult ALL

In the Chinese Guidelines for the Diagnosis and Treatment of Acute Lymphoblastic Leukemia in Adults (2016 edition), the main indicators of a good prognosis are as follows:

WBC <30×10⁹/L at diagnosis.

Immunophenotype: thymic T.

Genetics or gene expression profile

TEL-AML1(?). .

HOX11 overexpression (?) .

NOTCH1(?). .

9p deletion (?) Hyperdiploidy (?).

Hyperdiploid (?) .

Response to treatment

Good response to prednisone treatment (?). .

Time to reach CR (complete remission): early.

Tiny residual disease after CR Negative or <10-⁴.

Age: <25 years (or <35 years).

Other factors: compliance, tolerance and multidrug resistance.

[special alert].

“?” stands for possible significance, but no consensus has been reached.

The above prognostic factors are for reference only. Consultation with the attending physician is recommended for specific prognostic conditions.

Daily

Daily Management

Mindfulness and Emotional Adjustment

A good mood and mindset cannot be replaced by medication.

After diagnosis, patients may develop a sense of fear and may be afraid of pain, abandonment and death. Family members should pay attention to listen to the patient’s heart, improve the patient’s mental ability and relieve anxiety symptoms.

Encourage the patient’s family to give support so that the patient can face the surgery and other treatments positively with a good mindset.

During the period between treatments and after treatment, family members are advised to encourage the patient to do work and household chores that are within their ability, so as to reintegrate into their social roles.

Living

The living environment should be kept clean, with sufficient ventilation, sufficient sunlight and suitable greenhouse temperature. Disinfect the room regularly to avoid infection.

Maintain good hygiene and cleanliness to prevent accidental bodily injury. Rinse your mouth with saline solution and use a soft-bristled toothbrush after meals and before bedtime.

Maintain a positive and optimistic state of mind, reduce tension and anxiety, and avoid excessive activity and trauma for those who are prone to bleeding.

Dietary regulation

Balanced dietary structure, diversified food types and rich nutrition.

Pickled, fried and deep-fried food should be avoided.

Eat more vitamin-rich vegetables and fruits, such as broccoli, tomatoes, celery, lettuce, kiwi, apples and bananas.

Eat more protein-rich foods, such as eggs, milk, lean meat and fish.

It is recommended not to eat foods that stimulate the secretion of stomach acid, such as foods that are too sweet and spicy.

Rest and Exercise

Pay attention to rest, avoid staying up late or straining, and ensure sufficient sleep and rest to reduce physical exertion and promote recovery.

When the condition improves, start with low intensity exercise such as walking and gradually resume normal activities.

Review and follow up

Hematopoietic Stem Cell Transplant

Patients who have received hematopoietic stem cell transplants need to strictly follow the doctor’s instructions for follow-up examinations in order to monitor and prevent complications.

At present, most hospitals in China adopt the following post-transplantation review program:

Time and Frequency

Every 3 months

Every 6 months for 2 to 3 years

2nd to 3rd year

Every 6 months

After 3 years: 1 time per year

After 3 years

1 time per year

RemarksIf there is any discomfort, you can come to the clinic at any time.

Remarks

You can come to the clinic at any time if you feel unwell

Review program

The main items of the post-transplantation review include

Physical examination.

Laboratory tests, such as blood test, bone marrow test and genetic test.

Organ function and endocrine function monitoring, etc.

Follow-up for patients who have not received hematopoietic stem cell transplantation

These patients, need to strictly follow the doctor’s instructions for follow-up, usually return to the hospital for review every 3 to 6 months.