Leukemia is the most common malignant tumor in children, with an incidence rate of about 4 per 100,000 among children under 15 years old, accounting for approximately 35% of all malignant tumors in this age group. In China, an average of about 15,000 children under 15 develop leukemia each year. Its characteristic is the malignant proliferation of leukemia cells in the bone marrow, which infiltrate other tissues and organs, leading to a series of clinical symptoms. After the founding of the People's Republic of China, with the development of child healthcare, the incidence and mortality rates of infectious diseases and other pestilences gradually declined, and malignant tumors have become the leading cause of death in children. Therefore, reducing the mortality rate of leukemia and improving its treatment methods are currently important tasks in the field of pediatrics.

bubble_chart Etiology

Although extensive research has been conducted, the disease cause has not yet been fully elucidated. It is currently believed to be associated with the following factors.

1. **Viral Factors** The role of RNA tumor viruses in causing leukemia in animals such as mice, cats, chickens, and cattle has been confirmed. Leukemia caused by these viruses is mostly of the T-cell type. In recent years, human T-cell leukemia virus (HTLV), a type C retrovirus, has been isolated from patients with adult T-cell leukemia and lymphoma. Antibodies against HTLV structural proteins have also been detected in the serum of Japanese T-cell leukemia patients. However, no clear relationship between such viruses and childhood leukemia has been identified so far.
2. **Chemical Factors** Certain chemicals are known to cause leukemia. For example, populations exposed to benzene and its derivatives have a higher incidence of leukemia than the general population. Reports also suggest that substances such as nitrosamines, phenylbutazone and its derivatives, and chloramphenicol may induce leukemia, though statistical data are lacking. Some cytotoxic drugs used in cancer treatment, such as nitrogen mustard, cyclophosphamide, procarbazine, VP16, and VM26, are widely recognized to have leukemogenic effects.
3. **Radiation Factors** There is conclusive evidence that various conditions of ionizing radiation can cause leukemia in humans. The occurrence of leukemia depends on the dose of radiation absorbed by the body. Both whole-body and partial-body exposure to moderate or high doses of radiation can induce leukemia. However, it remains uncertain whether low-dose radiation can cause leukemia. After the atomic bomb explosions in Hiroshima and Nagasaki, the incidence of leukemia in heavily irradiated areas was 17 to 30 times higher than in non-irradiated areas. The incidence increased year by year, peaking 5 to 7 years after the explosions. It took 21 years for the incidence to return to levels close to those of the rest of Japan. Workers exposed to radiation and those frequently handling radioactive materials show a significantly increased incidence of leukemia. Additionally, radiation-based diagnostic and therapeutic procedures can lead to an elevated risk of leukemia.
4. **Genetic Factors** Populations with chromosomal abnormalities have a higher incidence of leukemia than normal individuals. For example, children with trisomy 21 (Down syndrome) have a 1 in 74 chance of developing leukemia before the age of 10. The incidence is 1 in 3 for Bloom syndrome by age 26 and 1 in 12 for Fanconi syndrome by age 21. When one family member develops leukemia, the probability of a close relative developing the disease is four times higher than in the general population. In monozygotic twins, if one develops acute leukemia, the other has a 20–25% chance of also developing it. These observations suggest that the disease cause of leukemia may be related to genetics. Recent studies have confirmed that numerical chromosomal abnormalities, such as gains or losses of chromosomes, as well as structural abnormalities like translocations, inversions, and deletions, lead to abnormal gene structure and expression. Aberrant gene expression and/or gene inactivation are among the fundamental mechanisms underlying malignant transformation of cells.

bubble_chart Type

(1) Acute Leukemia

Acute leukemia is a group of primary malignant hematologic disorders of the hematopoietic system, characterized by the abnormal proliferation of leukemia cells in the bone marrow and other hematopoietic tissues, as well as their infiltration into other organs, leading to the failure of normal hematopoietic function and a significant reduction in normal hematopoietic cells. The main clinical manifestations include fever, bleeding, anemia, and enlargement of the liver, spleen, and lymph nodes. It is generally believed that the occurrence of this disease is related to ionizing radiation, certain chemical agents, drugs, viruses, and genetic factors, and is also influenced by the immune status and humoral factors of the body. These factors lead to the malignant transformation of hematopoietic cells, the unlimited proliferation of malignant leukemia cells, and their infiltration into the bone marrow and other tissues, ultimately resulting in a significant reduction of normal hematopoietic cells, uncontrolled bleeding, and fatal infections. From a clinical treatment perspective, we classify this disease into two main categories: acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL), each with its own subtypes.

(2) Acute Lymphoblastic Leukemia (ALL) is divided into three subtypes—L1, L2, and L3—based on cytomorphology and clinical prognosis:

1. L1: Predominantly small lymphocytes with scanty cytoplasm, a high nuclear-to-cytoplasmic ratio, regular nuclear shape, uniformly dense chromatin, and indistinct nucleoli.
2. L2: Most cells are twice the size of small lymphocytes, with significant heterogeneity in cell size. The cytoplasm is moderate and basophilic, with chromatin appearing diffuse and finely granular or densely clumped. Nucleoli are distinct, one or more.
3. L3: Composed of uniformly large cells with abundant, deeply basophilic cytoplasm containing multiple prominent vacuoles. The nucleus is round, with fine and dense chromatin, and distinct nucleoli, one or more.

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These subtypes are closely related to clinical prognosis. The prognosis of L1 is better than that of L2, while L3 is difficult to achieve remission and has a poor prognosis.

(3) Acute Myeloid Leukemia (AML) is clinically divided into seven subtypes:

1. M1: (Acute minimally differentiated myeloblastic leukemia) Characterized by the proliferation of undifferentiated or poorly differentiated myeloblasts, classified as Type I and Type II. Type I cells lack cytoplasmic granules, while Type II cells contain a few azurophilic granules or Auer rods. The combined percentage of Type I and Type II myeloblasts is ≥90%, with promyelocytes to mature granulocytes and monocytes accounting for less than 10%.
2. M2: (Acute partially differentiated myeloblastic leukemia) Further divided into two subtypes.
   1. M2a: Myeloblasts in the bone marrow >30%, monocytes <20%，早幼粒細胞以下階段> 10%;
   2. M2b: A significant increase in abnormal myeloblasts and promyelocytes in the bone marrow, with abnormal neutrophilic myelocytes predominating, accounting for >30%.
3. M3: (Acute promyelocytic leukemia) Predominantly abnormal promyelocytes, often >30%, divided into two subtypes: M3a (coarse granular) and M3b (fine granular).
4. M4: (Acute myelomonocytic leukemia) This type exhibits varying proportions of granulocytic and monocytic cells in the bone marrow and peripheral blood, divided into four subtypes:
   1. M4a: Predominantly myeloblasts and promyelocytes, with myeloblasts, promonocytes, and monocytes >20%;
   2. M4b: Predominantly myeloblasts, promonocytes, and monocytes, with myeloblasts and promyelocytes >20%;
   3. M4c: Myeloblasts exhibiting both granulocytic and monocytic morphological features >30%;
   4. M4eo: In addition to the above features, eosinophils with coarse, round, and deeply stained granules account for 5–30%.
5. M5: (Acute monocytic leukemia) Monocytic series cells in the bone marrow ≥80%, including primitive monocytes, immature monocytes, and mature monocytes, divided into 2 subtypes:
   1. M5a (undifferentiated type): Primitive monocytes >80%.
   2. M5b (partially differentiated type): Primitive cells and immature monocytes >30%, primitive monocytes <80%。
6. M6: (Acute erythroleukemia) Characterized by proliferation of erythroid precursor cells with dysplastic hematopoiesis and increased bone marrow blast cells. Nucleated red blood cells >50%, myeloblasts or immature monocytes >30%, and myeloblasts or primitive monocytes in blood smears >75%.
7. M7: (Acute megakaryoblastic leukemia) Primitive or immature megakaryoblasts in bone marrow or peripheral blood ≥30%, divided into two types:
   1. Undifferentiated type: Bone marrow primitive megakaryoblasts >30%,
   2. Differentiated type: Bone marrow and peripheral blood predominantly show mononuclear and multinuclear dysplastic megakaryocytes.

(4) Special types of acute leukemia

1. Hypoplastic acute leukemia: Peripheral blood shows pancytopenia, occasional blasts, generally no hepatosplenomegaly, bone marrow hypoplasia, decreased nucleated cells, primitive cells >30%, and bone marrow biopsy shows hypoplasia.
2. Adult T-cell leukemia: Superficial lymphadenopathy, polymorphonuclear lymphocytes in peripheral blood >10%, belonging to the T-cell type.
3. Plasma cell leukemia: Plasma cells in peripheral blood >20% or absolute count ≥2.0×10⁹/L; bone marrow shows significant plasma cell proliferation with increased primitive and immature plasma cells and morphological abnormalities.
4. Mast cell leukemia: Clinical manifestations of leukemia or mastocytosis, lymphadenopathy, hepatosplenomegaly, mast cells in peripheral blood, significant mast cell proliferation in bone marrow accounting for >50% of nucleated cells; increased urinary histamine.
5. Eosinophilic leukemia: Peripheral blood shows significant and persistent eosinophilia, often up to 60%, with abnormal immature eosinophils; bone marrow shows increased eosinophils, morphological abnormalities, left shift, and various stages of immature eosinophils.
6. Basophilic leukemia: Peripheral blood shows significant basophilia with abnormal immature basophils; bone marrow shows numerous basophilic primitive cells >5%, increased basophilic early, middle, and late myelocytes, and left shift.
7. Mixed-lineage leukemia: Refers to a group of diseases in acute leukemia involving both myeloid and lymphoid lineages. Can be divided into three types based on cell origin and expression.
   1. Biphenotypic leukemia: Each cell simultaneously expresses both myeloid and lymphoid lineage characteristics.
   2. Biclonal leukemia: Leukemia cells are heterogeneous, with some expressing myeloid lineage characteristics and others expressing lymphoid lineage characteristics.
   3. Bilineal leukemia: Similar to biclonal leukemia, but both leukemia cell lineages originate from the same pluripotent stem cell.
8. Central nervous system leukemia:
   1. Presence of central nervous system symptoms and signs;
   2. Cerebrospinal fluid changes with leukemia cells visible in smears;
   3. Exclusion of other causes of similar central nervous system or cerebrospinal fluid changes.

(5) Chronic leukemia

1. Chronic myeloid leukemia (CML): CML is a clonal disease caused by mutation of pluripotent stem cells, characterized by proliferation and accumulation of mature granulocytes and their precursors, including granulocytic, monocytic, erythroid, and megakaryocytic lineages, as well as some B-lymphoid lineages. Clinically divided into three stages based on disease progression: chronic phase, accelerated phase, and blast crisis.
2. Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease characterized by the proliferation and accumulation of mature lymphocytes in the blood, bone marrow, lymph nodes, liver, spleen, and other organs. It is clinically classified into two types: T-cell type and B-cell type.

(6) Myelodysplastic Syndrome (MDS)

MDS is a syndrome characterized by abnormal proliferation and differentiation of hematopoietic stem cells. Its features include anemia, which may be accompanied by infection or bleeding, pancytopenia or reduction in any one or two blood cell lineages in peripheral blood, and hypercellular or markedly hypercellular bone marrow (though a minority may show hypoplasia). All three blood cell lineages exhibit significant dyshematopoiesis, with possible increases in myeloblasts or promyelocytes, but without meeting the diagnostic criteria for acute leukemia. This disease is also referred to as "preleukemia." The cause of primary MDS is unknown, while secondary MDS is associated with certain hematological conditions, radiation or chemotherapy, leading to malignant clonal growth of bone marrow hematopoietic stem cells and resulting in ineffective hematopoiesis. The disease is classified into five subtypes:

1. Refractory anemia (RA)
2. Refractory anemia with ringed sideroblasts (RAS)
3. Refractory anemia with excess blasts (RAEB)
4. Refractory anemia with excess blasts in transformation (RAEB-t)
5. Chronic myelomonocytic leukemia (CMML).

bubble_chart Clinical Manifestations

Patients with leukemia often present with infection and fever as the main symptoms. The vast majority of patients have a very high white blood cell count in their blood. Although the number of white blood cells is high, they are immature and underdeveloped cells, akin to "child soldiers" with no ability to resist pathogens. As a result, leukemia patients are highly susceptible to infections. When areas such as the mouth, throat, ears, nose, anus, or skin are affected, inflammatory changes may occur. If the invading bacteria are highly virulent and enter the bloodstream, they can lead to "sepsis," which is life-threatening. Because the bone marrow of leukemia patients produces large quantities of immature white blood cells, the megakaryocytes responsible for platelet production are significantly reduced. Consequently, leukemia patients may experience bleeding in the skin, mucous membranes, and multiple tissues or organs. In severe cases, intracranial hemorrhage can occur. When leukemia cells invade other tissues, symptoms may include bone pain, tumors on the bone membrane (chloroma), skin nodules, swollen gums, and enlargement of the liver, spleen, and lymph nodes. Additionally, conditions such as meningeal leukemia and testicular leukemia may develop. Most leukemia patients also suffer from anemia, which can worsen due to bleeding.

bubble_chart Treatment Measures

With the development and progress of medicine, the treatment level for acute leukemia has significantly improved. People are no longer merely satisfied with achieving complete remission (CR) in patients but are committed to research aimed at ultimately enabling long-term disease-free survival or even a cure. Current treatment methods for leukemia include chemotherapy, {|###|}integration of Chinese and Western medicine{|###|} therapy, bone marrow transplantation, biological regulator therapy, and gene therapy, among others.

1. Chemotherapy

In June 1946, the first case of leukemia remission through chemotherapy abroad marked the dawn of a new era in leukemia treatment. By the 1970s, strategies such as combination chemotherapy, maintenance therapy, and consolidation therapy had gradually been refined. In recent years, with the application of new anti-leukemia drugs, treatment efficacy has made substantial progress. The latest research indicates that the CR rate for childhood acute lymphoblastic leukemia (ALL) has reached 85–95%, with a 5-year disease-free survival rate of ≥50–70%. For adult ALL, the CR rate is close to 75–85%, with a 5-year disease-free survival rate of ≥40–50%. For adult acute myeloid leukemia (AML), the CR rate is 65–85%, and long-term disease-free survival for patients under 60 can reach 40–50%. As research in leukemia treatment advances, efficacy continues to improve, bringing hope for a cure. To achieve this goal, it is essential to tailor treatment based on each patient's unique characteristics, integrating modern therapeutic approaches. Leukemia treatment must be viewed holistically, with particular attention to individual factors such as age, gender, leukemia type, hematological features, cytogenetic and molecular biological characteristics, and leukemia cell kinetics. On this basis, an optimal treatment plan should be designed, rationally utilizing modern methods such as chemotherapy, hematopoietic stem cell transplantation, biological and gene therapy, and {|###|}integration of Chinese and Western medicine{|###|} therapy. These approaches should complement and coordinate with each other to minimize toxic {|###|}side effects{|###|}, eradicate leukemia cells, and achieve long-term survival or even a cure.

Chemotherapy is generally divided into: - **Induction therapy** (chemotherapy administered initially to achieve CR); - **Consolidation therapy** (chemotherapy similar to induction therapy after CR is achieved); - **Maintenance therapy** (chemotherapy with lower intensity and milder bone marrow suppression than induction therapy); - **Intensification therapy** (chemotherapy with stronger regimens than induction therapy), including early intensification and {|###|}advanced stage{|###|} intensification.

The key principles of chemotherapy are early intervention, adequate dosage, combination therapy, and individualized treatment. Increasing chemotherapy {|###|}dose{|###|} and intensity is one of the main factors improving CR rates and long-term survival in leukemia patients. When CR is achieved, although leukemia cells in bone marrow morphology classification are reduced to <5%，但機體內的白血病細胞總數仍可高達10^6-9, without timely post-CR intensification, leukemia cells can rapidly proliferate, leading to relapse and the development of drug {|###|}resistance{|###|}. Therefore, leukemia patients should undergo prompt and effective post-CR treatment.

Since the 1980s, combination chemotherapy has been widely adopted for leukemia treatment. This approach emphasizes the cell cycle and sequential drug use, typically selecting drugs that act on different cell cycles, enhance each other's leukemia cell-killing effects, have differing or mutually mitigating toxic {|###|}side effects{|###|}, and exhibit relative selectivity in targeting leukemia cells.

The principle of individualized chemotherapy for leukemia is a necessary development in leukemia treatment research, emphasizing four key aspects: (1) Different chemotherapy regimens should be selected for different types of leukemia. For ALL, drugs, doses, and treatment courses distinct from those for AML should be chosen. (2) Treatment plans should be tailored and differentiated for leukemia cases with varying prognostic factors. For example, in T-ALL and B-ALL, adding CTX, MTX, or Ara-C to conventional regimens can significantly improve CR rates and survival. (3) The patient's pre-chemotherapy health status is also a critical consideration for individualized treatment. Drug doses should be reduced for patients with liver, kidney, or heart dysfunction. (4) Close monitoring of blood and bone marrow changes during chemotherapy is essential, with timely adjustments to chemotherapy doses based on specific conditions.

Reasons for failure of leukemia chemotherapy: Chemotherapy failure is mainly due to early death caused by infection and hemorrhage during the chemotherapy period, or the ineffectiveness due to drug resistance of leukemia cells. Generally, failure can be categorized into the following situations: (1) Complete drug resistance of leukemia cells, manifested as bone marrow hyperplasia suppression after chemotherapy but no reduction in leukemia cells; (2) Partial drug resistance of leukemia cells, manifested as partial reduction of leukemia cells after chemotherapy, but unsatisfactory results followed by re-proliferation of leukemia cells; (3) Bone marrow hypoplasia, with no recovery of bone marrow hematopoiesis four weeks after chemotherapy; (4) Bone marrow hypoplasia leading to death within four weeks; (5) Early death due to uncontrolled hemorrhage or infection during chemotherapy; (6) Complete remission (CR) after chemotherapy but with extramedullary leukemia still present. Additionally, a small number of patients experience rapid reduction of leukemia cells after chemotherapy, accompanied by swift suppression of bone marrow and blood counts, but soon afterward, leukemia cells and WBC rapidly proliferate again, leading to rapid deterioration of the condition. Such cases are difficult to manage, have poor prognosis, and lack effective treatment methods.

II. Integration of Chinese and Western Medicine Treatment

Integration of Chinese and Western Medicine treatment can complement each other's strengths. Chinese medicine can compensate for the indiscriminate killing effect of Western chemotherapy, as well as address the issue of drug resistance to chemotherapy. Additionally, for some hypoplastic leukemias where white blood cells and platelets are already very low and cannot withstand strong chemotherapy drugs, Chinese medicine can be used for treatment. This not only avoids the toxic side effects of Western drugs but also alleviates the condition. Integration of Chinese and Western Medicine treatment can take the following forms.

1. Pure Chinese medicine treatment is suitable for hypoplastic leukemia patients who cannot tolerate chemotherapy. It is also applicable to patients who have never used chemotherapy drugs from the onset of the disease and have not yet developed drug resistance. Chinese medicine treatment is suitable for patients whose blast cell counts are not very high. By adhering to daily medication, complete remission (CR) can usually be achieved within a certain period (generally 3–4 months). Our hospital has proposed a new method called "cell reversal therapy" for treating leukemia, which is similar to the Western concept of induced differentiation. This approach involves a combination of drugs to remove stasis, purify blood, strengthen the body, and detoxify, effectively controlling the proliferation of leukemia cells and gradually transforming and decomposing them while also killing some leukemia cells. Furthermore, it regulates the immune system, enhances metabolism, and facilitates the elimination of toxins from the body. Through comprehensive and targeted regulation of the body, the goal of curing leukemia can be achieved. Traditional Chinese medicine has brought hope to leukemia treatment. We will conduct further research in this area to explore safer and more effective treatment methods for leukemia.
2. Combination of Chinese and Western medicine involves supporting the body with Chinese medicine after chemotherapy to elevate white blood cells and platelets, enhance immune function, and resist infection and bleeding. Chinese medicine can still be used during the remission stage of chemotherapy, both to promote recovery and to consolidate the effects of chemotherapy, thereby extending the interval between chemotherapy sessions.

III. Biological Modifier Therapy

With advancements in immunology and gene technology, biological modifier therapy has been applied clinically. Interleukin-II, various hematopoietic growth factors such as GM-CSF, G-CSF, M-GCSF, erythropoietin, tumor necrosis factor, and interferon have been clinically validated. Interleukin-II and LAK cells have shown certain efficacy in treating leukemia. G-CSF and GM-CSF, when used in patients with bone marrow suppression after chemotherapy, can significantly shorten the suppression period of bone marrow and blood counts, accelerate remission, and reduce complications.

IV. Gene Therapy

Gene therapy involves introducing exogenous genes into target cells (tissues) to correct, compensate for, or suppress certain abnormal or defective genes, thereby achieving therapeutic goals. Its treatment methods can be divided into four categories: (1) Gene compensation: Introducing genes with normal function into target cells to compensate for missing or inactive genes. (2) Gene correction: Eliminating the original abnormal gene and replacing it with an exogenous gene. (3) Gene substitution: The expression level of the exogenous normal gene exceeds that of the original abnormal gene. (4) Antisense technology: Using artificially synthesized or biologically synthesized specific complementary DNA or RNA fragments or their chemically modified products to inhibit or block the expression of abnormal or missing genes.

Gene therapy for leukemia, as a novel approach, is gradually transitioning from theoretical research to clinical trials. In the United States, it has already passed the Phase II clinical trial stage. Currently, gene therapy primarily focuses on the use of antisense oligonucleotides to block proto-oncogenes. Antisense technology, which does not require altering the gene structure, can target the gene and its products for treatment, making it the simplest and most straightforward method in gene therapy. CML is the leukemia most extensively studied using antisense nucleic acid technology. With improvements in existing techniques and the use of retroviral vectors, including multiple antisense DNA/RNA and auxiliary gene systems such as the BCR/ABL fusion gene, breakthroughs in CML gene therapy are expected soon.

V. Bone Marrow Transplantation (BMT)

1. Allogeneic Bone Marrow Transplantation (Allo-BMT) involves administering ultra-high-dose radiotherapy and chemotherapy to the patient as pretreatment, followed by the implantation of hematopoietic stem cells from healthy bone marrow into the patient to reconstruct their hematopoietic and immune functions.

The use of bone marrow to treat diseases began in 1891 when Brown-Sequard administered oral bone marrow to treat anemia. In 1939, Osgood performed the first intravenous infusion of bone marrow. In 1951, Lorenz et al. successfully conducted the first bone marrow transplantation experiment. Since the 1970s, advancements in HLA tissue typing technology and in-depth research in transplant immunology and other basic medical fields have rapidly expanded the clinical application of BMT. BMT centers have been established worldwide, and significant progress has also been made in China. In recent years, the number of Allo-BMT cases in China has exceeded 300, with efficacy levels comparable to international standards.

The long-term disease-free survival rate of Allo-BMT for leukemia is approximately 50%. According to the 1993 statistics from the International BMT Registry, the five-year survival rates for BMT-treated leukemia are as follows: acute lymphoblastic leukemia (ALL) in first complete remission (CR1) is about 50%, ALL in second complete remission (CR2) or higher is about 32%, relapsed ALL is about 18%, acute myeloid leukemia (AML) in CR1 is about 52%, AML in CR2 or beyond is about 35%, chronic myeloid leukemia (CML) in the chronic phase is about 45%, in the accelerated phase is about 36%, and in the blast phase is about 6%. This indicates that leukemia patients should undergo BMT as soon as possible after achieving CR through chemotherapy.

The risks of BMT primarily lie in two aspects: first, there are many transplantation-related complications, and second, leukemia relapse remains a concern post-BMT. The main transplantation-related complications include hepatic veno-occlusive disease, with an incidence rate of 25% and a mortality rate of 80%, and graft-versus-host disease, with an incidence rate of 10–80%. The leukemia relapse rate post-BMT is approximately 15–30%.

Steps of Allo-BMT:

1. 1. Select an HLA (human leukocyte antigen) fully matched donor. The selection priority is as follows: an HLA-genotype-matched sibling, followed by an HLA-phenotype-matched family member, then a family member with one HLA-mismatch or an unrelated HLA-phenotype-matched donor, and finally an unrelated donor with one HLA-mismatch or a family member with two or three HLA mismatches.
2. 2. Preparation of the recipient: Verify and confirm the diagnosis and classification of leukemia. Generally, the recipient's age should be limited to under 45–50 years, with normal function of vital organs. All potential infection sites in the body must be cleared. A comprehensive physical examination and necessary laboratory tests (typically over ten auxiliary tests) are required. The recipient should be admitted to a sterile laminar airflow room one week in advance.
3. 3. Perform histocompatibility antigen and gene typing.
4. The BMT preconditioning should last for three months, aiming to achieve three objectives: first, to destroy the recipient's original hematopoietic cells, creating space for the engraftment and growth of the transplanted hematopoietic stem cells. Second, to suppress the recipient's immune cells and functions, facilitating the successful engraftment of the bone marrow. Third, to extensively eliminate and eradicate leukemia cells within the recipient's body.
5. Collection, processing, and infusion of bone marrow: On the day of bone marrow infusion, the donor's bone marrow is collected under sterile conditions in the operating room. After filtration, it is intravenously infused to the recipient as soon as possible to avoid loss of hematopoietic stem cells. Bone marrow from ABO-incompatible donors must be processed before infusion.
6. The BMT process apoplexy involving meridians often requires essential nutritional and supportive therapy.
7. Early prevention and treatment of BMT complications, elimination of digestive tract toxic reaction, and control of various infections, bleeding, and other major complications.
8. Prevention and treatment of advanced-stage BMT complications, such as chronic graft-versus-host disease.
9. Hematopoietic reconstitution and engraftment evidence in BMT: After BMT, patients undergo the process of original hematopoietic system failure and hematopoietic reconstitution of the newly implanted bone marrow. The gradual increase in reticulocytes after BMT is considered an early indicator of bone marrow engraftment. Peripheral blood counts typically return to normal within 3–6 months. Additionally, detection of red blood cell antigens, white blood cell antigens, and cytogenetic analysis can directly confirm the success of BMT engraftment.
10. Relapse of leukemia after BMT: Generally, older patients have a higher relapse rate, as do those not in their first complete remission and CML patients not in the chronic phase. Patients receiving a lower TBI (total body irradiation) dose during BMT preconditioning also have a higher relapse rate, with most relapses (95%) being of the recipient type. The main causes of relapse are incomplete clearance of leukemia cells during BMT (i.e., a higher residual leukemia cell load in the body) and insufficient graft-versus-leukemia effect after BMT.

2. Autologous stem cell transplantation and umbilical bleeding hematopoietic stem cell transplantation

The so-called "autologous stem cell transplantation" involves collecting autologous hematopoietic stem cells before high-dose chemotherapy or radiotherapy to protect them from injury, followed by reinfusion after high-dose chemotherapy or radiotherapy. Autologous hematopoietic stem cells can be sourced from bone marrow or collected from the patient's peripheral blood. Since autologous stem cell transplantation does not involve complications like graft-versus-host disease, it can be used for older patients. The steps involve collecting hematopoietic stem cells, preserving them at above- and below-zero temperatures, thawing them for reinfusion, and purifying autologous stem cells while eliminating residual white blood cells before transplantation. Patients undergo necessary examinations and preconditioning with chemotherapy or radiotherapy, followed by supportive treatments such as infection and bleeding control post-transplantation. Autologous stem cell transplantation yields better outcomes than conventional chemotherapy, with some reports considering it an effective consolidation therapy after complete remission in acute leukemia. However, its drawback is a high relapse rate, and there is no consensus on survival duration or underlying reasons.

Umbilical bleeding hematopoietic stem cell transplantation was first performed worldwide in 1988, and many researchers have since engaged in this field. Compared to BMT, umbilical bleeding transplantation shows slightly delayed engraftment, lower incidence of severe GVHD when HLA matching has 1–2 mismatched loci, minimal response to hematopoietic factors, and limitations due to the finite number of umbilical bleeding cells (restricting recipient weight to <40 kg). Currently, umbilical cord blood hematopoietic cell banks have been established worldwide. Although the number of cases conducted in China remains limited and conclusions await further evaluation, this research area holds great promise.

bubble_chart Prognosis

The median survival time for untreated acute leukemia is 3.3 months. In recent years, due to advances in treatment, the prognosis has significantly improved. The complete remission rate for childhood {|###|}heat stranguria{|###|} reaches 97-100%, with a 5-year disease-free survival rate of 50-75%. For adults, the complete remission rate for {|###|}heat stranguria{|###|} is around 80%, and the 5-year disease-free survival rate is 50%. The complete remission rate for acute non-lymphocytic leukemia is 70-85%, with a 5-year disease-free survival rate of 35-50%, and some patients achieve a cure. However, estimating the prognosis of leukemia is very challenging. Generally, the main factors affecting prognosis are differences in the biological characteristics of leukemia, such as cell type, cell count, cytogenetics, and immunology. Other factors include the patient's age and {|###|}constitution{|###|} status.

The course of chronic leukemia varies greatly, ranging from as short as 1–2 years to as long as 10–20 years, with an average survival period of 5 years. The primary factor affecting the prognosis of chronic myeloid leukemia is its transformation into acute leukemia. Once it progresses to acute leukemia, the prognosis is worse than that of primary acute leukemia. The most common cause of death in chronic myeloid leukemia is infection, particularly pulmonary infection.

bubble_chart Complications

1. Infection: Due to leukemia, the normal white blood cells decrease, especially the neutrophils. Factors such as chemotherapy also lead to a deficiency of granulocytes, making patients prone to severe infections or sepsis. Common bacteria causing infections include Gram-positive bacteria, such as Staphylococcus aureus, hemolytic streptococci, and Corynebacterium, as well as Gram-negative bacilli, such as Pseudomonas aeruginosa, Escherichia coli, and Klebsiella. Fungal infections, such as those caused by Candida albicans, Aspergillus, Mucor, and Trichosporon, often occur in patients with prolonged granulocytopenia or persistent fever unresponsive to antibiotics. Some patients undergoing corticosteroid therapy
are more susceptible to viral infections due to impaired cellular immune function, such as varicella-zoster virus and herpes simplex virus. Additionally, Pneumocystis carinii infections are also common
, with upper respiratory infections and pneumonia being the typical manifestations.

2. Intestinal Failure: Chemotherapy drugs and radiotherapy used in leukemia treatment can impair gastrointestinal function, leading to intestinal failure. Nutritional supplementation becomes a critical issue for these patients. Currently, subclavian vein catheterization into the superior vena cava for high-nutrition infusion only partially addresses the problem. Nutritional deficiencies can result in complications such as pneumonia and enteritis.

3. Hyperuric Hemorrhagic Syndrome: In healthy individuals, nucleic acid metabolism breaks down, excreting 300–500 mg of uric acid in urine daily. Leukemia patients may excrete uric acid dozens of times more due to the massive breakdown of leukemic cell nucleic acids. When patients undergo chemotherapy or radiotherapy, hyperuricemia occurs, and the use of corticosteroids can further exacerbate it. High concentrations of uric acid quickly become supersaturated and precipitate, causing widespread renal tubular

injury and uric acid stones, which may lead to oliguria or anuria. Therefore, leukemia patients must receive adequate fluids to ensure sufficient urine output and take allopurinol. If renal failure occurs, fluid intake must be restricted, and dialysis may be necessary. 4. Hemorrhage: Due to the malignant proliferation of leukemic cells and a significant decrease in platelets, leukemia patients are prone to bleeding in the respiratory, digestive, and urinary tracts, especially intracranial hemorrhage. Therefore, active hemostatic measures must be taken based on the

disease cause, including the infusion of concentrated platelets. 5. Pulmonary Diseases: The reduction of mature neutrophils and impaired immune function in leukemia patients often lead to pulmonary infections. Additionally, leukemic cell infiltration can block small pulmonary blood vessels and bronchi, causing dyspnea and acute respiratory distress syndrome. Chest X-rays may show ground-glass opacity or miliary reticular patterns, and experimental lung radiation therapy may be considered.

6. Electrolyte Imbalance: During leukemia treatment, excessive destruction of leukemic cells or chemotherapy-induced kidney damage can lead to excessive potassium excretion. Poor appetite and digestive dysfunction caused by chemotherapy may result in insufficient intake and hypokalemia. Alternatively, the destruction of leukemic cells may release more phosphorus, leading to hypocalcemia. Therefore, attention must be paid to the concentrations of potassium, calcium, sodium, and other electrolytes during treatment.

7. Disseminated Intravascular Coagulation (DIC): Disseminated intravascular coagulation is a severe hemorrhagic syndrome.