Advertisement

Three patients with multiple myeloma developing secondary lymphoblastic leukemia: case reports and review of the literature

Abstract

Introduction

Secondary lymphoblastic leukemia has been rarely reported in patients with multiple myeloma.

Case reports

We report 3 cases of secondary lymphoblastic leukemia in multiple myeloma patients. They shared a similar phenotype of myeloma cells and secondary lymphoblasts. The chemotherapy treatments in the 3 patients were complex due to various factors.

Conclusions

Multiple immune defects caused by exposure to a variety of agents can play an important role in the development of secondary lymphoblastic leukemia. Microscopic morphology and flow cytometry are important means to detect secondary malignancies in multiple myeloma. Further clinical, experimental and genetic studies of secondary malignancies in multiple myeloma will be necessary in the future.

Tumori 2016; 102(Suppl. 2): e131 - e136

Article Type: CASE REPORT

DOI:10.5301/tj.5000377

Authors

Li Junxun, Liu Junru, Chen Meilan, Liang Chujia, Chen Shaoqian, Zhan Jieyu, Ye Zhuangjian, Zhang Fan, Ouyang Juan, Cheng Jing, Li Juan

Article History

Disclosures

Financial support: None.
Conflict of interest: The authors declare that they have no competing interests.

This article is available as full text PDF.

Download any of the following attachments:

Introduction

Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by plasma cells accumulating in the bone marrow, with subsequent destruction of bone, symptoms of bone marrow failure, and organ dysfunction (1, 2). Recent studies have shown that acute myeloid leukemia (AML) and myelodysplasia (MDS) may represent secondary hematological malignancies of MM (3-4-5-6); however, cases of secondary lymphoblastic leukemia in MM have rarely been reported (3-4-5-6). In this article, we report 3 cases of secondary lymphoblastic leukemia occurring after complex therapy with bortezomib, dexamethasone, thalidomide and anthracyclines. We then provide a brief review of the literature.

Case reports (Tab. I)

Case 1

Characteristics and treatment of patients in the present study and in the literature

Case 1 2 3 Lau (7) Ueda (8) Piszcz (9)
MM = multiple myeloma; VDJ = variable - diversity - junctional; ASCT = autologous stem cell transplant; CR = complete remission; nCR = near-complete remission; NR = non remission; PR = partial response; MLL = mixed lineage leukemia gene rearrangement; VADM = vincristine, pirarubicin, dexamethasone, melphalan; PAD = bortezomib, dexamethasone, doxorubicin; DVD = doxorubicin, vincristine, dexamethasone; VAD = vincristine, doxorubicin, dexamethasone; VCMP = vincristine, cyclophosphamide, melphalan, prednisone; VD = bortezomib, dexamethasone; VTD = bortezomib, dexamethasone, thalidomide; MPT = melphalan, prednisolone, thalidomide.
Regimens used
Case 1
VADM regimen: vincristine 0.5 mg from day 1 to day 4; pirarubicin 10 mg from day 1 to day 4; dexamethasone 20 mg from day 1 to day 4; melphalan 12 mg from day 1 to day 4
VD regimen: bortezomib 2.0 mg on days 1, 4, 7 and 11, dexamethasone 20 mg/day on days 1, 2, 4, 5, 7, 8, 11 and 12
Case 2
PAD regimen: bortezomib 2.5 mg days 1, 4, 8 and 11, dexamethasone 10 mg days 1-4, doxorubicin hydrochloride 60 mg day 4
VTD regimen: bortezomib 2.5 mg days 1, 4, 8 and 13; dexamethasone 20 mg days 1-4; thalidomide 200 mg/day
Case 3
DVD regimen: doxorubicin 60 mg/day 1, vincristine 2 mg/day 1, dexamethasone 10 mg/days 1-4
VD regimen: bortezomib 1.9 mg days 1, 4, 8 and 11, dexamethasone 20 mg days 1-4
Case Lau et al (7)
VAD regimen
Case Ueda et al (8)
High-dose dexamethasone
Case Piszcz et al (9)
VCMP regimen
MPT regimen
Age at MM diagnosis (years) 66 60 33 60 61 56
Durie-Salmon stage IIA IIIB IIIB IIIA
Immunoglobulin/level IgG-κ/78 g/L IgG-κ/97.1 g/L IgG-λ/42.1 g/L IgG-κ IgD-λ IgG
Plasma cell % in bone marrow 19% 67% 16.5% 50% 50% 11.2%
Hemocytopenia at primary MM No No Anemia Anemia / /
VDJ rearrangement Positive Negative Positive Positive Positive /
Induction therapy VADM 2 cycles PAD 4 cycles DVD 1 cycle VAD 4 cycles High-dose dexamethasone 4 cycles VCMP 7 cycles
Responsiveness to chemotherapy CR nCR NR CR Very good PR PR
Consolidation therapy VD 2 cycles VTD 1 cycle VD 4 cycles / / MPT 9 cycles
Radiation therapy No 20 times No No No No
ASCT No 4 months after diagnosis 4 months after diagnosis 6 months after diagnosis 7 months after diagnosis No
Maintenance therapy Lenalidomide/thalidomide Thalidomide Thalidomide High-dose melphalan (140 mg/m2) High-dose melphalan (200 mg/m2) Thalidomide
CR duration 34 months 32 months 73 months 35 months 11 months (PR) 52 months (PR)
Age at lymphoblastic leukemia diagnosis (years) 65 63 39 63 62 65
Percentage of lymphoblasts 68% 84% 84% 90% 94% 37.8%
VDJ rearrangement Positive Positive / Positive Positive /
BCR/ABL Negative Negative Negative / / Negative
MLL Negative Negative Negative Negative Positive Negative

In July 2009, a 65-year-old female Han Chinese patient was admitted to our hospital with bone pain as chief complaint. A metastatic bone survey (MBS) of the skeleton revealed multiple focal osteolytic lesions. Complete blood count was normal. Serum protein electrophoresis revealed the presence of a monoclonal protein in the gamma region, which was subsequently identified as IgG immunoglobulin and kappa light chain. Plasma cells accounted for 19% of the nucleated cells in the bone marrow (Fig. 1A). The results of flow cytometric analysis (CD38+, CD138+, CD19–, CD56+, CD54+, CD20–, CD49e–) were consistent with the presence of clonal plasma cells.

The myeloma cells and lymphoblast in the patients’ bone marrow smears. (A) Myeloma cells of case 1 before treatment. The myeloma cells were different from normal plasma cells in that they were large with irregular nuclei, fine chromatin, small nucleoli, and atypical cytoplasmic features. (B) Lymphoblasts of case 1. The lymphoblasts were characterized by round nuclei with a fine chromatin structure, 1 to 2 nucleoli per cell, and scant cytoplasm without granules. (C) Myeloma cells of case 2 before treatment. The myeloma cells were characterized by eccentrically placed round nuclei, a compact chromatin structure, and abundant, foamy, dark blue cytoplasm with perinuclear pale zone. (D) Lymphoblasts of case 2. The lymphoblasts were characterized by round nuclei with a fine chromatin structure, 1 to 2 nucleoli per cell, and scant cytoplasm with a small amount of vacuoles. (E) Myeloma cells of case 3 before treatment. The myeloma cells were characterized by their relatively small size, eccentric, round nuclei, fine chromatin, abundant blue cytoplasm, and small perinuclear pale zone. (F) Lymphoblasts of case 3. The lymphoblasts had round nuclei with a fine chromatin structure, 1-2 nucleoli per cell, and blue cytoplasm with vacuoles.

The patient was diagnosed with multiple myeloma (Durie-Salmon IIA) and received 2 cycles of the VADM regimen. Complete remission (CR) was achieved. Lenalidomide (10 mg/day) was used as maintenance therapy from September 11, 2009. However, due to financial constraints the patient refused further lenalidomide. She therefore received consolidation therapy with the VD regimen for 2 cycles from November 5, 2010. Thalidomide (200 mg/day) was used as maintenance therapy from February 1, 2010 to October 13, 2012.

The patient was readmitted to our hospital with serious dizziness of more than 10 days’ duration. This time, immunoelectrophoresis was normal. Lymphoblasts accounted for 68% of the nucleated cells in a bone marrow smear (Fig. 1B). The results of flow cytometric analysis (CD45+, CD19+, CD22+, CD34+, CD33 (dim), CD79a+, CD38–, CD138–, CD54–, CD20–, CD10–, HLA-DR+, CD103–, CD25–, CD11c–, CD5–, MPO–, CD13–, CD117–, ZAP-70–) were consistent with the presence of clonal lymphoblasts. According to MBS, the focal bone lesions still existed. Positron emission tomography-computed tomography (PET-CT) revealed an elevated SUVmax (maximum standardized uptake value of FDG) in axial bone (4.0). Based on these results, this MM patient was diagnosed as having secondary B-cell lymphoblastic leukemia. She declined further treatment and died of respiratory failure in February 2014.

Case 2

A 63-year-old male Han Chinese patient was admitted to our hospital in September 2010 with back pain as the chief complaint. With a medical history including hypertension and diabetes mellitus for 4 years, he was given Norvasc (5 mg/day), Levemir (20 IU QM) once monthly, NovoNorm (1 mg tid) and glucophage (0.5 g tid) as treatment. The results of flow cytometric analysis (CD38+, CD138+, CD19–, CD56+, CD54+, CD20–, CD49e–) were consistent with the presence of clonal plasma cells.

The patient was diagnosed with MM (Durie-Salmon IIIB) and given the PAD regimen for 4 cycles from December 2010 to March 2011. The patient achieved near-complete remission (nCR). With informed consent, the patient underwent autologous stem cell transplantation (ASCT) on May 13, 2011.

However, follow-up PET-CT showed a high SUV in some of the focal osteolytic bone lesions, even after 20 radiotherapy sessions (2 Gy per fraction, directed to the left fifth rib). The VTD regimen was therefore given as consolidation ­therapy from September 1, 2011. After 1 course of therapy the ­patient achieved CR. He was started on thalidomide (200 mg/day) as maintenance therapy in October 2011.

He was readmitted to our hospital in May 2014 with serious fatigue as the chief complaint. Immunoelectrophoresis showed no monoclonal band. The patient had a low platelet count (33 × 109/L).

Lymphoblasts accounted for 84% of nucleated cells in the patient’s bone marrow smear (Fig. 1D). The results of flow cytometric analysis (CD10+, CD34+, HLA-DR+, CD33 (dim), CD19 (dim), CD2–, CD3–, CD13–, CD14–, CD20–, CD38–, CD138–, CD56–, CD64–, CD25–, CD11c–, CD5–, MPO–, CD117–, ZAP-70–) were consistent with common B-cell acute lymphoblastic leukemia (ALL). According to MBS, the focal bone lesions still existed. PET-CT revealed a slightly elevated SUV in the focal bone lesions. Based on these results, this MM patient was diagnosed as having secondary B-cell lymphoblastic leukemia. After the diagnosis, he gave up treatment and did not come back to our hospital.

Case 3

A 33-year-old female Han Chinese patient was admitted to our hospital in September 2006 with serious fatigue as chief complaint. MBS revealed multiple focal osteolytic bone lesions. Complete blood count showed a low hemoglobin level (51 g/L). Plasma cells accounted for 16.5% of the bone marrow cells (Fig. 1E). The results of flow cytometric analysis (CD38+, CD138+, CD19–, CD56+, CD54+, CD20–, CD49e–) were consistent with the presence of clonal plasma cells.

The patient was diagnosed with MM (Durie-Salmon IIIB). The DVD regimen was given for 1 cycle from December 2006; however, the patient did not benefit much from the treatment. Therefore the VD regimen was given for 4 cycles from April 2007. The patient achieved nCR and underwent ASCT on April 29, 2007.

Thalidomide (200 mg/day) was used as maintenance therapy from January 2008. The dosage was reduced to 150 mg/day because of mild numbness and dizziness. In March 2013, the patient was diagnosed with hypertension and was therefore prescribed valsartan (80 mg/day) and amlodipine (5 mg/day). CR was maintained until April 2014, when the patient was readmitted to our hospital with serious cough as chief complaint. Immunoelectrophoresis showed no monoclonal band. The level of beta-2 microglobulin (2,180 μg/L) was elevated while the level of hemoglobin (109 g/L) was slightly low. Plasma cells accounted for 2% and lymphoblasts for 84% of the nucleated cells in the bone marrow smear (Fig. 1F). The results of flow cytometric analysis (CD10+, CD34+, HLA-DR+, CD19+, CD22+, CD33+, CD79a+ CD2–, CD3–, CD13–, CD7–, CD20–, CD64–, CD25–, CD11c–, CD5–, MPO–, CD117–, ZAP-70–) were consistent with ALL. Based on these results, this MM patient was diagnosed as having secondary B-cell lymphoblastic leukemia. Because of financial constraints, the patient gave up treatment after the lymphoblastic leukemia diagnosis and did not come back to our hospital.

All the records of these 3 patients were reviewed. Unexpectedly, a very low percentage (<0.005%) of blast cells was found in their bone marrow smears during maintenance therapy (Fig. 2). The blast cells had scant agranular cytoplasm, no Auer rods, coarse to fine chromatin and indistinct nucleoli. The blast cells were not noticed during maintenance therapy.

Blast cells found in the bone marrow smears during maintenance therapy. Case 1 (A), case 2 (B) and case 3 (C). The blast cells in Figure 2A, 2B and 2C are similar to the lymphoblasts described in Figure 1A, 1C and 1E, respectively.

IgH rearrangements in the MM phase were positive in case 1 and case 3, and negative in case 2. IgH rearrangement in the lymphoblastic leukemia phase was positive in cases 1 and 2 (Fig. 3). A specimen of case 3 in the lymphoblastic leukemia phase was not available.

Fluorescence in situ hybridization results of the MM phase and ALL phase in the 3 cases. MM phase of case 1: positive (A); ALL phase of case 1: positive (B); MM phase of case 2: negative (C); ALL phase of case 2: positive (D); MM phase of case 3: positive (E). MM = multiple myeloma; ALL = acute lymphoblastic leukemia.

Discussion

In recent years, new agents have prolonged the survival of MM patients, but a concerning finding is the increased incidence of secondary malignancies (3-4-5-6). Mailankody et al (3) calculated the standardized incidence rates for all subsequent hematological and nonhematological malignancies for more than 8,740 MM patients. Sixty-nine and 508 of the patients were diagnosed with a second hematological and nonhematological malignancy, respectively (3). To our knowledge, most secondary hematological malignancies were either AML or MDS. Secondary lymphoblastic leukemia in MM is rarely seen and has been reported in only 3 published papers (7-8-9). In the present article we reported 3 cases of secondary lymphoblastic leukemia in MM and we tried to find out if there were any common characteristics.

Noticeably, all 3 patients shared a similar treatment process: they received bortezomib, anthracycline and dexamethasone either as induction or consolidation therapy and thalidomide as maintenance therapy. Furthermore, they underwent regimen changes during the course of treatment (for economic reasons or because of limited therapy effect), increasing the chances of exposure to more chemotherapeutics (Tab. I). Moreover, they showed a similar phenotype of the lymphoblasts: CD10+, CD34+, HLA-DR+ and CD33 (dim).

By contrast, 3 special cases were found by reviewing the 3 papers on secondary ALL mentioned above (7-8-9). All 3 patients received dexamethasone and melphalan but no ­bortezomib; furthermore, no CD33 expression was present in the lymphoblasts (Tab. I).

Bortezomib, which is linked to decreased numbers of NK cells and CD8+ T cells and alteration of dendritic cell function (10), was a principal medicine in the treatment of the 3 patients described by us. However, according to San Miguel et al (11) there was no significant difference in the incidences of secondary malignancies between a VMP (bortezomib, melphalan and prednison) group and an MP (melphalan and prednisone) group. Bortezomib was associated with a relatively low incidence of secondary malignancies. Our patients had short exposure to bortezomib (less than 2 months) and therefore we speculate that bortezomib may not be the main cause of the secondary lymphoblastic leukemia in our patients.

The exposure time to thalidomide in these 3 patients was relatively long (it lasted 32-73 months as maintenance therapy). However, thalidomide was associated with a relatively low incidence of secondary malignancies compared with other immunomodulatory agents. Studies have found that thalidomide can have both immunostimulatory and immunosuppressive activity. In vitro, thalidomide has been shown to exert a strong co-stimulatory effect on T cells, leading to increased levels of both IL-2 and IFN-γ, and these effects were most marked for CD8+ T cells (12). It has also been suggested that thalidomide can lead to an increased level of IL-5 but has no effect on IL-4 production (13). However, further details of its effect on T-cell function remained unclear.

Usmani and colleagues (14) compared the incidence of secondary malignancies between a control group (no thalidomide) and an experimental group (thalidomide for induction, consolidation and maintenance therapy and transplantation). No significant difference was observed. Stewart et al (15) conducted a randomized phase III trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM. They found that 8 (4.8%) and 6 (3.7%) patients developed secondary malignancies in the thalidomide-prednisone group and observation group, respectively. Though the difference was not calculated, it seemed not significant (15). These studies would suggest that the use of thalidomide does not increase the risk of secondary malignancies.

Further research has shown that melphalan seems to elevate the risk of secondary malignancies. According to Schütt et al (16), conventional-dose chemotherapy (melphalan, cyclophosphamide) with or without steroids reduced the numbers of CD4+(T helper) cells, CD4+/CD45RO+ cells (memory T cells) and CD19+ cells (B-lineage cells). In addition, high-dose chemotherapy was shown to prolong the observed immunosuppression. This resulted in an increased incidence of opportunistic infections such as cytomegalovirus infection, pneumocystic pneumonia, and varicella-zoster virus infection. Opportunistic infections were correlated with severely reduced CD4+ T-cell, CD4+/CD45RO+ cell and CD19+ cell counts (16). Furthermore, chemotherapy was associated with direct DNA damage and genetic mutations, potentially adversely impacting the immune system (17).

Bergsagel et al (18) carried out a prospective study on secondary malignanies in MM. They found that the incidence of MDS or acute leukemia was associated with long-term use of 3 alkylating agents: melphalan, cyclophosphamide and carmustine. Similar results from a study by Cuzick et al (19) indicated that the accumulated dose of melphalan in 3 years might be the main risk factor for secondary malignancies in MM.

Our 3 patients had received anthracyclines in their induction therapy. However, the therapeutic effects were unsatisfactory. Although anthracyclines are known to have ­cardiotoxicity, few papers have reported on its relation to triggering secondary tumors. Secker-Walker et al (20) reported that 14 of 40 patients with mixed lineage leukemia gene rearrangement (MLL) abnormalities who developed secondary tumors had received anthracyclines. Sandoval et al (21) inferred that anthracyclines may cause secondary AML if combined with either alkylating agents or irradiation. Case 1 of the present study had received pirarubicin combined with melphalan while case 2 received doxorubicin and subsequent irradiation. Yet, they both developed secondary ALL, but not AML.

CD33 is an important myeloid antigen. In the past, it was believed that the prognosis of ALL showing expression of myeloid antigen (Mye(+)ALL) was poorer than that of ALL with no myeloid antigen expression (Mye(–)ALL). However, recent papers suggested that there was no significant difference ­between the prognosis of these 2 groups (22-23-25). As previously mentioned, our 3 cases were different from those described in other reports. Their lymphoblasts presented CD33 expression in varying degrees. Our hypothesis is that this might be highly related to the patients’ similar medication regimens: they received bortezomib, anthracycline and dexamethasone either in induction or consolidation therapy and thalidomide in maintenance therapy. As mentioned above, anthracyclines may cause secondary AML if combined with alkylating agents or irradiation (21). However, our patients developed Mye(+)ALL.

According to the available literature, it was difficult to distinguish whether the secondary lymphoblastic leukemia of our 3 patients was triggered by any single agent during their treatment or not. The treatments of these 3 patients were complex due to various reasons. The change of chemotherapy regimen may have led these patients to be exposed to more chemotherapeutic drugs. As a result of the exposure to various agents, it could be inferred that multiple immune defects may have played a role in the development of secondary lymphoblastic leukemia in these 3 patients.

A very low percentage of blast cells was found in the bone marrow smears of our 3 patients during maintenance therapy. Based on the morphology of the blast cells, we supposed the lymphoblasts might have existed during maintenance therapy before lymphoblastic leukemia occurred. Further flow cytometric analysis revealed that the 3 patients shared a lymphoblast phenotype that was positive for CD10, CD34, HLA-DR and CD33 (from diminished to positive). We speculate that microscopic morphology and flow cytometry can be important in the detection of secondary malignancies in MM. Once abnormal cells are detected in bone marrow smears, further flow cytometry analysis should be performed. If monoclonal lymphoblasts are present, especially with an abnormal immunophenotype such as CD33 expression, secondary lymphoblastic leukemia is highly likely.

Unfortunately we did not have enough specimens to run IgH rearrangement tests for all 3 patients in both the MM and ALL phase. We did find that IgH rearrangement was negative in the MM phase but positive in the ALL phase in case 2. This would suggest that 2 distinct monoclonal B-cell populations participate in the pathogenesis of these 2 lymphoid malignancies at the 2 time points. This is consistent with the 3 reports describing the occurrence of secondary lymphoblastic leukemia in MM (7-8-9).

Conclusion

In conclusion, we reported on 3 MM patients who developed secondary lymphoblastic leukemia after complex treatments with bortezomib, anthracycline, dexamethasone and thalidomide. Multiple immune defects caused by exposure to a variety of agents might have existed in these patients and played an important role in the development of secondary lymphoblastic leukemia. Microscopic morphology and flow cytometry are important to the detection of secondary malignancies in MM. Although the administration of new agents prolongs the survival time of MM patients, further clinical, experimental and genetic studies of secondary malignancies in MM are necessary.

Disclosures

Financial support: None.
Conflict of interest: The authors declare that they have no competing interests.
References
  • 1. Junxun L Juan L Xiuzhen T Juan O Bohuang Z Junru L Comparing five diagnostic criteria for multiple myeloma: a retrospective study of 227 cases. Tumori 2014 100 2 207 213 Google Scholar
  • 2. Garcia MK Cohen L Guo Y et al. Electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy in multiple myeloma: a feasibility study. J Hematol Oncol 2014 7 1 41 Google Scholar
  • 3. Mailankody S Pfeiffer RM Kristinsson SY et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood 2011 118 15 4086 4092 Google Scholar
  • 4. Pan B Lentzsch S The application and biology of immunomodulatory drugs (IMiDs) in cancer. Pharmacol Ther 2012 136 1 56 68 Google Scholar
  • 5. Ormerod A Fausel CA Abonour R Kiel PJ Observations of second primary malignancy in patients with multiple myeloma. Clin Lymphoma Myeloma Leuk 2012 12 2 113 117 Google Scholar
  • 6. Srivastava G Rana V Lacy MQ et al. Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma. Leukemia 2013 27 10 2062 2066 Google Scholar
  • 7. Lau LG Tan LK Koay ES Liu TC Acute lymphoblastic leukemia after tandem autologous stem cell transplantations for multiple myeloma. Leukemia 2005 19 2 299 301 Google Scholar
  • 8. Ueda K Yamamoto G Shinohara A Hangaishi A Kurokawa M Early onset of acute lymphoblastic leukemia with MLL rearrangement after autologous stem cell transplantation for multiple myeloma. Ann Hematol 2009 88 8 813 814 Google Scholar
  • 9. Piszcz J Bolkun L Cichocka E Kloczko J Secondary acute lymphoblastic leukaemia in a multiple myeloma patient. Contemp Oncol (Pozn) 2012 16 6 593 595 Google Scholar
  • 10. Chanan-Khan A Sonneveld P Schuster MW et al. Analysis of herpes zoster events among bortezomib-treated ­patients in the phase III APEX study. J Clin Oncol 2008 26 29 4784 4790 Google Scholar
  • 11. San Miguel JF Schlag R Khuageva NK et al. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan-prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol 2013 31 4 448 455 Google Scholar
  • 12. Haslett PA Corral LG Albert M Kaplan G Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 1998 187 11 1885 1892 Google Scholar
  • 13. Verbon A Juffermans NP Speelman P et al. A single oral dose of thalidomide enhances the capacity of lymphocytes to secrete gamma interferon in healthy humans. Antimicrob Agents Chemother 2000 44 9 2286 2290 Google Scholar
  • 14. Usmani SZ Sexton R Hoering A et al. Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance. Blood 2012 120 8 1597 1600 Google Scholar
  • 15. Stewart AK Trudel S Bahlis NJ et al. A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial. Blood 2013 121 9 1517 1523 Google Scholar
  • 16. Schütt P Brandhorst D Stellberg W et al. Immune parameters in multiple myeloma patients: influence of treatment and correlation with opportunistic infections. Leuk Lymphoma 2006 47 8 1570 1582 Google Scholar
  • 17. Dasanu CA Immune alterations in untreated and treated multiple myeloma. J Oncol Pharm Pract 2012 18 2 257 263 Google Scholar
  • 18. Bergsagel DE Bailey AJ Langley GR et al. The chemotherapy on plasma-cell myeloma and the incidence of acute leukemia. N Engl J Med 1979 301 14 743 748 Google Scholar
  • 19. Cuzick J Erskine S Edelman D Galton DA A comparison of the incidence of the myelodysplastic syndrome and acute myeloid leukaemia following melphalan and cyclophosphamide treatment for myelomatosis. A report to the Medical Research Council’s working party on leukaemia in adults. Br J Cancer 1987 55 5 523 529 Google Scholar
  • 20. Secker-Walker LM Moorman AV Bain BJ Mehta AB Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities. EU Concerted Action 11q23Workshop. Leukemia 1998 12 5 840 844 Google Scholar
  • 21. Sandoval C Pui CH Bowman LC et al. Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation. J Clin Oncol 1993 11 6 1039 1045 Google Scholar
  • 22. Lahjouji A Bachir F Bennani S et al. The immunophenotype of adult T acute lymphoblastic leukemia in Morocco. Exp Oncol 2015 37 1 64 69 Google Scholar
  • 23. Liu B Li R Wu HJ Chen Y Clinical study on prognosis of acute leukemia subtypes Ly + AML and My + ALL. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2007 15 2 421 424 Google Scholar
  • 24. Jiang NG Chen XM Zhu HL et al. Immunophenotype characteristics and prognosis of acute leukemia patients with cross expressing lymphoid and myeloid lineage associated antigens. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2010 18 6 1405 1409 Google Scholar
  • 25. Lahjouji A Bachir F Bennani S et al. Clinical importance of myeloid antigen expression in Moroccan patients with adult B-lineage acute lymphoblastic leukemia. Neoplasma 2013 60 5 553 560 Google Scholar

Authors

Affiliations

  • Department of Laboratory Science, First Affiliated Hospital of Sun Yatsen University, Guangzhou - China
  • Department of Pediatrics, First Hospital of Baiyun District, Guangzhou - China
  • Department of Hematology, First Affiliated Hospital of Sun Yatsen University, Guangzhou - China

Article usage statistics

The blue line displays unique views in the time frame indicated.
The yellow line displays unique downloads.
Views and downloads are counted only once per session.

No supplementary material is available for this article.